PIONEER 7: Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation Versus Sitagliptin in Subjects With Type 2 Diabetes Mellitus.

Sponsor
Novo Nordisk A/S (Industry)
Overall Status
Completed
CT.gov ID
NCT02849080
Collaborator
(none)
504
83
2
30.2
6.1
0.2

Study Details

Study Description

Brief Summary

This trial is globally conducted. The aim of this trial is to investigate Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation versus Sitagliptin in Subjects with Type 2 Diabetes Mellitus.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
504 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation Versus Sitagliptin in Subjects With Type 2 Diabetes Mellitus
Actual Study Start Date :
Sep 20, 2016
Actual Primary Completion Date :
Feb 28, 2018
Actual Study Completion Date :
Mar 27, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Semaglutide flexible dosing (3, 7 or 14 mg)

Drug: semaglutide
Oral administration once-daily.

Active Comparator: Sitagliptin 100 mg

Drug: sitagliptin
Oral administration once-daily.

Outcome Measures

Primary Outcome Measures

  1. Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no) [Week 52]

    Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at week 52. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

Secondary Outcome Measures

  1. Change in Body Weight [Week 0, week 52]

    Change from baseline (week 0) in body weight was evaluated at week 52. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

  2. Change in HbA1c [Week 0, week 52]

    Change from baseline (week 0) in HbA1c was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  3. Change in FPG [Week 0, week 52]

    Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  4. Change in Body Weight (%) [Week 0, week 52]

    Relative change from baseline (week 0) in body weight (kg) was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  5. Change in BMI [Week 0, Week 52]

    Change from baseline (week 0) in body mass index (BMI) was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  6. Change in Waist Circumference [Week 0, week 52]

    Change from baseline (week 0) in waist circumference was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  7. Change in Total Cholesterol (Ratio to Baseline) [Week 0, Week 52]

    Change from baseline (week 0) in total cholesterol (mmol/L) at week 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  8. Change in LDL Cholesterol (Ratio to Baseline) [Week 0, week 52]

    Change from baseline (week 0) in low-density lipoprotein (LDL) cholesterol (mmol/L) at week 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  9. Change in HDL Cholesterol (Ratio to Baseline) [Week 0, week 52]

    Change from baseline (week 0) in high-density lipoprotein (HDL) cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  10. Change in Triglycerides (Ratio to Baseline) [Week 0, week 52]

    Change from baseline (week 0) in triglycerides (mmol/L) at week 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  11. Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) [Week 0, week 52]

    SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The 0-100 scale scores (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from baseline (week 0) in the domain scores and component summary (PCS and MCS) scores were evaluated at week 52. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period.

  12. Change in DTSQ [Week 0, Week 52]

    Change from baseline (week 0) in diabetes treatment satisfaction questionnaire - status (DTSQs) was evaluated at week 52. The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher scores indicate higher levels of treatment satisfaction for DTSQs items 1, 4 -8. For items 2 and 3 a higher score indicates a higher patient perceived experience of high blood sugars and low blood sugars, respectively. Thus, lower scores indicate a perception of blood glucose levels being "none of the time" unacceptably high (item 2) or low (item 3). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 1, 4-8. The score ranges 0-36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction. Results are based on the data from the in-trial observation period.

  13. Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol) AACE Target (Yes/no) [Week 52]

    Participants who achieved HbA1c less than or equal to 6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no) at week 52 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  14. Participants Who Achieve Weight Loss ≥5% (Yes/no) [Week 52]

    Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 52 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  15. Participants Who Achieve Weight Loss ≥10% (Yes/no) [Week 52]

    Participants who achieved weight loss more than or equal to 10% of their baseline body weight (yes/no) at week 52 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  16. Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no) [Week 52]

    Participants who achieved HbA1c less than 7.0 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) at week 52 is presented. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  17. Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) [Week 52]

    Participants who achieved HbA1c reduction more than or equal to 1% of their baseline HbA1c and weight loss of more than or equal to 3% of their baseline body weight (yes/no) at week 52 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  18. Time to Rescue Medication [Weeks 0-52]

    Presented results are the number of participants who had taken rescue medication anytime during the periods, from week 0 to week 52. Rescue medication was defined as any new anti-diabetic medication used as add-on to trial product and used for more than 21 days with the initiation at or after randomisation (week 0) and before last day on trial product, and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before last day on trial product. Results are based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

  19. Time to Additional Anti-diabetic Medication [Weeks 0-52]

    Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the period from week 0 to week 52. Additional anti-diabetic medication was defined as any new anti-diabetic medication used for more than 21 days with the initiation at or after randomisation (week 0) and before (planned) end-of-treatment (week 52), and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before (planned) end-of-treatment. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  20. Number of TEAEs During Exposure to Trial Product [Week 0-57]

    Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 57 (52-week treatment period for participants who continued in the extension phase; 52-week treatment period plus the 5-week follow-up period for participants who did not continue in the extension phase). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period: Time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  21. Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes [Week 0-57]

    Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-57 (52-week treatment period for participants who continued in the extension phase; 52-week treatment period plus the 5-week follow-up period for participants who did not continue in the extension phase). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

  22. Paticipants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no) [Week 0-57]

    Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-57 (52-week treatment period for participants who continued in the extension phase; 52-week treatment period plus the 5-week follow-up period for participants who did not continue in the extension phase). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

  23. Change in Amylase (Ratio to Baseline) [Week 0, Week 52]

    Change from baseline (week 0) in biochemical parameter- amylase (units per liter [U/L]) to week 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  24. Change in Lipase (Ratio to Baseline) [Week 0, Week 52]

    Change from baseline (week 0) in lipase (U/L) to week 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  25. Change in Pulse Rate [Week 0, week 52]

    Change from baseline (week 0) in pulse rate was evaluated at week 52. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  26. Change in Blood Pressure (Systolic and Diastolic Blood Pressure) [Week 0, week 52]

    Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at week 52. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  27. Change in HbA1c- Switch [Week 52, week 104]

    Change from week 52 in HbA1c was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  28. Change in Body Weight- Switch [Week 52, week 104]

    Change from week 52 in body weight was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  29. Change in Body Weight (%)- Switch [Week 52, week 104]

    Relative change from week 52 in body weight (kg) was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  30. Change in FPG- Switch [Week 52, week 104]

    Change from week 52 in fasting plasma glucose (FPG) was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  31. Change in BMI- Switch [Week 52, Week 104]

    Change from week 52 in body mass index (BMI) was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  32. Change in Waist Circumference- Switch [Week 52, week 104]

    Change from week 52 in waist circumference was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  33. Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no)- Switch [Week 104 (i.e., after 52 weeks of treatment in the extension phase)]

    Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at week 104. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  34. Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol) AACE Target (Yes/no)- Switch [Week 104 (i.e., after 52 weeks of treatment in the extension phase)]

    Participants who achieved HbA1c less than or equal to 6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no) at week 104 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  35. Participants Who Achieve Weight Loss ≥5% (Yes/no)- Switch [Week 104 (i.e., after 52 weeks of treatment in the extension phase)]

    Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 104 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  36. Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)- Switch [Week 104 (i.e., after 52 weeks of treatment in the extension phase)]

    Participants who achieved HbA1c less than 7.0% without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) at week 104 is presented. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  37. Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target and no Need for Rescue Medication (Yes/no)- Switch [Week 104 (i.e., after 52 weeks of treatment in the extension phase)]

    Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) and no need for rescue medication (yes/no), was evaluated at week 104. Results are based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

  38. Time to Additional Anti-diabetic Medication- Switch [Weeks 53-104]

    Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the period from week 53 to week 104. Additional anti-diabetic medication was defined as any new anti-diabetic medication used for more than 21 days with the initiation at or after re-randomisation (week 52) and before (planned) end-of-treatment (week 104), and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before (planned) end-of-treatment. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  39. Time to Rescue Medication- Switch [Weeks 53-104]

    Presented results are the number of participants who had taken rescue medication anytime during the periods, from week 53 to week 104. Rescue medication was defined as any new anti-diabetic medication used as add-on to trial product and used for more than 21 days with the initiation at or after re-randomisation (week 52) and before last day on trial product, and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before last day on trial product. Results are based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

  40. Number of TEAEs During Exposure to Trial Product- Switch [Week 53-109]

    Treatment emergent adverse events (TEAEs) were recorded from week 53 to week 109. Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period: Time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  41. Change in Amylase (Ratio to Baseline)- Switch [Week 52, Week 104]

    Change from week 52 in biochemical parameter- amylase (U/L) to week 104 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  42. Change in Lipase (Ratio to Baseline)- Switch [Week 52, Week 104]

    Change from week 52 in lipase (U/L) to week 104 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  43. Change in Pulse Rate- Switch [Week 52, week 104]

    Change from week 52 in pulse rate was evaluated at week 104. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  44. Change in Blood Pressure (Systolic and Diastolic Blood Pressure)- Switch [Week 52, week 104]

    Change from week 52 in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at week 104. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  45. Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes- Switch [Week 53-109]

    Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 53 to 109. Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

  46. Paticipants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)- Switch [Week 53-109]

    Number of participants with treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 53 to 109. Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

  47. Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)- Switch [Week 52, week 104]

    SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The 0-100 scale scores (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from week 52 in the domain scores and component summary (PCS and MCS) scores were evaluated at week 104. A positive change score indicates an improvement since week 52. Results are based on the data from the in-trial observation period.

  48. Change in DTSQ- Switch [Week 52, week 104]

    Change from week 52 in diabetes treatment satisfaction questionnaire - status (DTSQs) was evaluated at week 104. The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher scores indicate higher levels of treatment satisfaction for DTSQs items 1, 4 -8. For items 2 and 3 a higher score indicates a higher patient perceived experience of high blood sugars and low blood sugars, respectively. Thus, lower scores indicate a perception of blood glucose levels being "none of the time" unacceptably high (item 2) or low (item 3). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 1, 4-8. The score ranges 0-36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction. Results are based on the data from the in-trial observation period.

  49. Change in HbA1c- Sustainability [Week 0, week 104]

    Change from baseline (week 0) in HbA1c was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  50. Change in Body Weight (kg)- Sustainability [Week 0, week 104]

    Change from baseline (week 0) in body weight was evaluated at week 104. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  51. Change in Body Weight (%)- Sustainability [Week 0, week 104]

    Relative change from baseline (week 0) in body weight (kg) was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  52. Change in FPG- Sustainability [Week 0, week 104]

    Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  53. Change in BMI- Sustainability [Week 0, Week 104]

    Change from baseline (week 0) in body mass index (BMI) was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  54. Change in Waist Circumference- Sustainability [Week 0, week 104]

    Change from baseline (week 0) in waist circumference was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  55. Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no)- Sustainability [Week 104]

    Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at week 104. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  56. Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol) AACE Target (Yes/no)- Sustainability [Week 104]

    Participants who achieved HbA1c less than or equal to 6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no) at week 104 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  57. Participants Who Achieve Weight Loss ≥5% (Yes/no)- Sustainability [Week 104]

    Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 104 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  58. Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)- Sustainability [Week 104]

    Participants who achieved HbA1c less than 7.0 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) at week 104 is presented. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  59. Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target or HbA1c Reduction ≥ 1%-Point (10.9 mmol/Mol) (Yes/no)- Sustainability [Week 104]

    Participants who achieved HbA1c <7.0% ADA target or HbA1c reduction ≥ 1%-point (10.9 mmol/mol) (yes/no), was evaluated at week 104. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  60. Number of TEAEs During Exposure to Trial Product- Sustainability [Week 0-109]

    Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 109 ((104-week treatment period for participants who continued in the extension phase or 52-week treatment period for participants who did not continue in the extension phase) plus the 5-week follow-up period). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period: Time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  61. Change in Amylase (Ratio to Baseline)- Sustainability [Week 0, week 104]

    Change from baseline (week 0) in biochemical parameter- amylase (units per liter [U/L]) to week 104 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  62. Change in Lipase (Ratio to Baseline)- Sustainability [Week 0, Week 104]

    Change from baseline (week 0) in lipase (U/L) to week 104 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  63. Change in Pulse Rate- Sustainability [Week 0, week 104]

    Change from baseline (week 0) in pulse rate was evaluated at week 104. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  64. Change in Blood Pressure (Systolic and Diastolic Blood Pressure)- Sustainability [Week 0, week 104]

    Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at week 104. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  65. Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes)- Sustainability [Week 0-109]

    Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-109 ((104-week treatment period for participants who continued in the extension phase or 52-week treatment period for participants who did not continue in the extension phase) plus the 5-week follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

  66. Paticipants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)- Sustainability [Week 0-109]

    Number of participants with treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-109 ((104-week treatment period for participants who continued in the extension phase or 52-week treatment period for participants who did not continue in the extension phase) plus the 5-week follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

  67. Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)- Sustainability [Week 0, week 104]

    Short form (SF)-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The 0-100 scale scores (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from baseline (week 0) in the domain scores and component summary (PCS and MCS) scores were evaluated at week 104. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period.

  68. Change in DTSQ- Sustainability [Week 0, week 104]

    Change from week 0 in diabetes treatment satisfaction questionnaire - status (DTSQs) was evaluated at week 104. The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher scores indicate higher levels of treatment satisfaction for DTSQs items 1, 4 -8. For items 2 and 3 a higher score indicates a higher patient perceived experience of high blood sugars and low blood sugars, respectively. Thus, lower scores indicate a perception of blood glucose levels being "none of the time" unacceptably high (item 2) or low (item 3). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 1, 4-8. The score ranges 0-36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction. Results are based on the data from the in-trial observation period.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

Main phase (the inclusion criteria for the main phase are not reassessed for the extension phase):

  • Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial

  • Male or female, age above or equal to 18 years at the time of signing informed consent. For Korea only: Male or female, age above or equal to 19 years at the time of signing informed consent

  • Diagnosed with type 2 diabetes mellitus for at least 90 days prior to day of screening

  • HbA1c (glycosylated haemoglobin) 7.5-9.5% (58-80 mmol/mol) (both inclusive)

  • Treatment target of HbA1c below 7.0% (53 mmol/mol), as judged by the investigator

  • Stable daily dose(s) of 1-2 of the following anti-diabetic drugs within 90 days prior to the day of screening:

  • Metformin (equal or above 1500 mg or maximum tolerated dose as documented in the subject medical record)

  • Sulfonylureas (equal or above half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record)

  • Sodium glucose co-transporter 2 inhibitors

  • Thiazolidinediones (equal or above half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record)

Extension phase:
  • Informed consent for the extension phase obtained before any trial-related activities for the extension phase.

  • On randomised treatment with or without rescue medication at week 52.

Exclusion Criteria:

Main phase (the exclusion criteria for the main phase are not reassessed for the extension phase):

  • Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice). For certain specific countries: Additional specific requirements apply

  • Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol

  • Family or personal history of Multiple Endocrine Neoplasia Type 2 or Medullary Thyroid Carcinoma

  • History of pancreatitis (acute or chronic)

  • History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery)

  • Any of the following: myocardial infarction, stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening and randomisation

  • Subjects presently classified as being in New York Heart Association Class IV

  • Planned coronary, carotid or peripheral artery revascularisation known on the day of screening

  • Subjects with alanine aminotransferase above 2.5 x upper normal limit

  • Renal impairment defined as Estimated Glomerular Filtration rate 60 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration formula

  • Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening. An exception is short-term insulin treatment for acute illness for a total of below or equal to 14 days

  • Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation

  • History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ)

  • History of diabetic ketoacidosis

Extension phase: There are no new exclusion criteria for the extension phase

Contacts and Locations

Locations

Site City State Country Postal Code
1 Novo Nordisk Investigational Site Glendale Arizona United States 85306-4652
2 Novo Nordisk Investigational Site Phoenix Arizona United States 85050
3 Novo Nordisk Investigational Site Lancaster California United States 93534
4 Novo Nordisk Investigational Site West Hills California United States 91304
5 Novo Nordisk Investigational Site Boynton Beach Florida United States 33472
6 Novo Nordisk Investigational Site Lake Worth Florida United States 33461
7 Novo Nordisk Investigational Site Miami Lakes Florida United States 33014
8 Novo Nordisk Investigational Site Port Orange Florida United States 32127
9 Novo Nordisk Investigational Site Tampa Florida United States 33607
10 Novo Nordisk Investigational Site Tampa Florida United States 33614
11 Novo Nordisk Investigational Site Atlanta Georgia United States 30318
12 Novo Nordisk Investigational Site Blackfoot Idaho United States 83221
13 Novo Nordisk Investigational Site Evanston Illinois United States 60201-2477
14 Novo Nordisk Investigational Site Greenfield Indiana United States 46140
15 Novo Nordisk Investigational Site Muncie Indiana United States 47304
16 Novo Nordisk Investigational Site Louisville Kentucky United States 40213
17 Novo Nordisk Investigational Site Metairie Louisiana United States 70002
18 Novo Nordisk Investigational Site Oxon Hill Maryland United States 20745
19 Novo Nordisk Investigational Site Flint Michigan United States 48504
20 Novo Nordisk Investigational Site Billings Montana United States 59101
21 Novo Nordisk Investigational Site Henderson Nevada United States 89052-2649
22 Novo Nordisk Investigational Site Albuquerque New Mexico United States 87109-2134
23 Novo Nordisk Investigational Site Chapel Hill North Carolina United States 27514
24 Novo Nordisk Investigational Site Greensboro North Carolina United States 27408
25 Novo Nordisk Investigational Site Greenville North Carolina United States 27834
26 Novo Nordisk Investigational Site Whiteville North Carolina United States 28472
27 Novo Nordisk Investigational Site Cleveland Ohio United States 44122
28 Novo Nordisk Investigational Site Mentor Ohio United States 44060
29 Novo Nordisk Investigational Site Wadsworth Ohio United States 44281
30 Novo Nordisk Investigational Site Pittsburgh Pennsylvania United States 15236
31 Novo Nordisk Investigational Site Murrells Inlet South Carolina United States 29576
32 Novo Nordisk Investigational Site Myrtle Beach South Carolina United States 29572
33 Novo Nordisk Investigational Site Kingsport Tennessee United States 37660
34 Novo Nordisk Investigational Site Corpus Christi Texas United States 78413
35 Novo Nordisk Investigational Site Dallas Texas United States 75231
36 Novo Nordisk Investigational Site Chesapeake Virginia United States 23321
37 Novo Nordisk Investigational Site Renton Washington United States 98057
38 Novo Nordisk Investigational Site Caba Argentina C1180AAX
39 Novo Nordisk Investigational Site Corrientes Argentina 3400
40 Novo Nordisk Investigational Site Rosario Argentina S2000DNM
41 Novo Nordisk Investigational Site Graz Austria 8036
42 Novo Nordisk Investigational Site Saint Stefan Austria 8511
43 Novo Nordisk Investigational Site Wien Austria 1130
44 Novo Nordisk Investigational Site Bonheiden Belgium 2820
45 Novo Nordisk Investigational Site Boussu Belgium 7300
46 Novo Nordisk Investigational Site Bruxelles Belgium 1200
47 Novo Nordisk Investigational Site Edegem Belgium 2650
48 Novo Nordisk Investigational Site Gent Belgium 9000
49 Novo Nordisk Investigational Site Leuven Belgium 3000
50 Novo Nordisk Investigational Site Liège Belgium 4000
51 Novo Nordisk Investigational Site São Paulo Sao Paulo Brazil 01228-200
52 Novo Nordisk Investigational Site Alexandria Egypt 21131
53 Novo Nordisk Investigational Site Cairo Egypt 11562
54 Novo Nordisk Investigational Site Cairo Egypt 11591
55 Novo Nordisk Investigational Site Gangwon-do Korea, Republic of 26426
56 Novo Nordisk Investigational Site Gyeonggi-do Korea, Republic of 15355
57 Novo Nordisk Investigational Site Pusan Korea, Republic of 602-739
58 Novo Nordisk Investigational Site Seoul Korea, Republic of 03080
59 Novo Nordisk Investigational Site Seoul Korea, Republic of 03722
60 Novo Nordisk Investigational Site Seoul Korea, Republic of 08308
61 Novo Nordisk Investigational Site Suwon Korea, Republic of 16499
62 Novo Nordisk Investigational Site Hamar Norway 2317
63 Novo Nordisk Investigational Site Oslo Norway 0373
64 Novo Nordisk Investigational Site Oslo Norway 0586
65 Novo Nordisk Investigational Site Stavanger Norway 4011
66 Novo Nordisk Investigational Site Trondheim Norway 7027
67 Novo Nordisk Investigational Site Bern Switzerland 3010
68 Novo Nordisk Investigational Site Einsiedeln Switzerland 8840
69 Novo Nordisk Investigational Site Genève 14 Switzerland 1211
70 Novo Nordisk Investigational Site Luzern 16 Switzerland 6000
71 Novo Nordisk Investigational Site Olten Switzerland 4600
72 Novo Nordisk Investigational Site St. Gallen Switzerland 9007
73 Novo Nordisk Investigational Site St. Gallen Switzerland 9016
74 Novo Nordisk Investigational Site Winterthur Switzerland 8401
75 Novo Nordisk Investigational Site Adana Turkey 01130
76 Novo Nordisk Investigational Site Ankara Turkey 06100
77 Novo Nordisk Investigational Site Antalya Turkey 07058
78 Novo Nordisk Investigational Site Istanbul Turkey 34096
79 Novo Nordisk Investigational Site Istanbul Turkey 34722
80 Novo Nordisk Investigational Site Istanbul Turkey 34752
81 Novo Nordisk Investigational Site Istanbul Turkey 34890
82 Novo Nordisk Investigational Site Istanbul Turkey 34899
83 Novo Nordisk Investigational Site Rize Turkey 53020

Sponsors and Collaborators

  • Novo Nordisk A/S

Investigators

None specified.

Study Documents (Full-Text)

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT02849080
Other Study ID Numbers:
  • NN9924-4257
  • 2015-005593-38
  • U1111-1177-5103
First Posted:
Jul 29, 2016
Last Update Posted:
Jul 20, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details The main phase of the trial was conducted at 77 sites in 10 countries, and the extension phase (Switch) at 71 sites in 9 countries, as follows (main phase/extension phase): Argentina (3/3), Austria (3/3), Belgium (7/7), Brazil (2/0), Egypt (4/4), Norway (4/4), South Korea (7/7), Switzerland (8/5), Turkey (8/8), and United States (31/30).
Pre-assignment Detail The trial consisted of two treatment periods: a 52-week main phase and a 52-week extension phase. In Switch, participants were allowed to re-randomise from sitagliptin to oral semaglutide. Sustainability included results for participants who received oral semaglutide during main + extension phase.
Arm/Group Title Oral Semaglutide Flex Sitagliptin 100 mg- Main Phase Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants who were still on treatment at week 52 were allowed to continue on oral semaglutide in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial. Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Period Title: Main Phase: 0 - 52 Weeks
STARTED 253 251 0 0
Exposed 253 250 0 0
Full Analysis Set (FAS) 253 251 0 0
Safety Analysis Set (SAS) 253 250 0 0
COMPLETED 241 244 0 0
NOT COMPLETED 12 7 0 0
Period Title: Main Phase: 0 - 52 Weeks
STARTED 185 0 100 98
Exposed 184 0 100 97
COMPLETED 182 0 99 98
NOT COMPLETED 3 0 1 0

Baseline Characteristics

Arm/Group Title Oral Semaglutide Flex Sitagliptin 100 mg Total
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants who were still on treatment at week 52 were allowed to continue on oral semaglutide in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial. Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants who were still on treatment at week 52 were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial. Total of all reporting groups
Overall Participants 253 251 504
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
57
(10)
58
(10)
57
(10)
Sex: Female, Male (Count of Participants)
Female
108
42.7%
111
44.2%
219
43.5%
Male
145
57.3%
140
55.8%
285
56.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
48
19%
57
22.7%
105
20.8%
Not Hispanic or Latino
205
81%
194
77.3%
399
79.2%
Unknown or Not Reported
0
0%
0
0%
0
0%
Race/Ethnicity, Customized (Count of Participants)
White
195
77.1%
186
74.1%
381
75.6%
Black or African American
22
8.7%
25
10%
47
9.3%
Asian
34
13.4%
38
15.1%
72
14.3%
American Indian or Alaska Native
0
0%
0
0%
0
0%
Native Hawaiian or other Pacific Islander
0
0%
0
0%
0
0%
Other
2
0.8%
2
0.8%
4
0.8%

Outcome Measures

1. Primary Outcome
Title Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no)
Description Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at week 52. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.
Time Frame Week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = full analysis set (FAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 253 251
Yes
134
53%
60
23.9%
No
96
37.9%
178
70.9%
Yes
123
48.6%
52
20.7%
No
73
28.9%
132
52.6%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Semaglutide Flex- Main Phase, Sitagliptin 100 mg- Main Phase
Comments The analysis was based on a pattern mixture model using multiple imputation to handle missing week 52 data, assuming that data were missing at random within the groups used for imputation. The imputed data sets were analysed using a logistic regression model with treatment, strata, and region as categorical fixed effects and baseline HbA1c value as covariate for each of the 1000 imputed complete datasets, and pooled by Rubin's rule to draw inference.
Type of Statistical Test Superiority
Comments This hypothesis was controlled for multiplicity. Results are based on the data from the in-trial observation period. The estimated treatment effect includes the effect of any rescue medication and any effect after premature trial product discontinuation (treatment policy estimand).
Statistical Test of Hypothesis p-Value <0.0001
Comments Unadjusted two-sided p-value for test of no difference from 1.
Method Pattern mixture model
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.40
Confidence Interval (2-Sided) 95%
2.89 to 6.70
Parameter Dispersion Type:
Value:
Estimation Comments Oral Semaglutide flex / Sitagliptin 100 mg.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Oral Semaglutide Flex- Main Phase, Sitagliptin 100 mg- Main Phase
Comments The analysis was based on multiple imputation, imputing sequentially using post-baseline measurements up to and including week 52. The imputed data sets were analysed using a logistic regression model with treatment, strata, and region as categorical fixed effects and baseline HbA1c value as covariate for each of the 1000 imputed complete datasets, and pooled by Rubin's rule to draw inference.
Type of Statistical Test Superiority
Comments This hypothesis was not controlled for multiplicity. Results are based on the data from the on-treatment without rescue medication observation period. The estimated treatment effect excludes the effect of any rescue medication and any effect after premature trial product discontinuation (hypothetical estimand).
Statistical Test of Hypothesis p-Value <0.0001
Comments Unadjusted two-sided p-value for test of no difference from 1.
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.54
Confidence Interval (2-Sided) 95%
3.54 to 8.68
Parameter Dispersion Type:
Value:
Estimation Comments Oral Semaglutide flex / Sitagliptin 100 mg
2. Secondary Outcome
Title Change in Body Weight
Description Change from baseline (week 0) in body weight was evaluated at week 52. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.
Time Frame Week 0, week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 253 251
In-trial
-2.7
(3.9)
-0.7
(3.5)
On-treatment without rescue medication
-2.9
(4.0)
-0.9
(3.6)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Semaglutide Flex- Main Phase, Sitagliptin 100 mg- Main Phase
Comments The analysis was based on a pattern mixture model using multiple imputation to handle missing week 52 data, assuming that data were missing at random within the groups used for imputation. The imputed data sets were analysed using a logistic regression model with treatment, strata, and region as categorical fixed effects and baseline HbA1c value as covariate for each of the 1000 imputed complete datasets, and pooled by Rubin's rule to draw inference.
Type of Statistical Test Superiority
Comments This hypothesis was controlled for multiplicity. Results are based on the data from the in-trial observation period. The estimated treatment effect includes the effect of any rescue medication and any effect after premature trial product discontinuation (treatment policy estimand).
Statistical Test of Hypothesis p-Value <0.0001
Comments Unadjusted two-sided p-value for test of no difference from 0.
Method Pattern mixture model
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.9
Confidence Interval (2-Sided) 95%
-2.6 to -1.2
Parameter Dispersion Type:
Value:
Estimation Comments Oral semaglutide flex - Sitagliptin 100 mg
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Oral Semaglutide Flex- Main Phase, Sitagliptin 100 mg- Main Phase
Comments The analysis was based on a Mixed model for repeated measurements (MMRM) that assumed data to be missing at random. As dependent variables, the MMRM model included all post-baseline values collected at scheduled visits up to and including week 52. The independent effects were treatment, strata and region as categorical fixed effects and the baseline HbA1c value as a covariate, all nested within visit, and an unstructured residual covariance matrix.
Type of Statistical Test Superiority
Comments This hypothesis was not controlled for multiplicity. Results are based on the data from the on-treatment without rescue medication observation period. The estimated treatment effect excludes the effect of any rescue medication and any effect after premature trial product discontinuation (hypothetical estimand).
Statistical Test of Hypothesis p-Value <0.0001
Comments Unadjusted two-sided p-value for test of no difference from 0.
Method Mixed model for repeated measurements
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-2.9 to -1.5
Parameter Dispersion Type:
Value:
Estimation Comments Oral semaglutide flex - Sitagliptin 100 mg
3. Secondary Outcome
Title Change in HbA1c
Description Change from baseline (week 0) in HbA1c was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 0, week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 230 238
Mean (Standard Deviation) [Percentage of HbA1c]
-1.3
(0.9)
-0.8
(1.0)
4. Secondary Outcome
Title Change in FPG
Description Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 0, week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 229 232
Mean (Standard Deviation) [Millimoles per liter (mmol/L)]
-2.41
(2.35)
-1.39
(3.13)
5. Secondary Outcome
Title Change in Body Weight (%)
Description Relative change from baseline (week 0) in body weight (kg) was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 0, week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 233 239
Mean (Standard Deviation) [Percentage change]
-2.99
(4.42)
-0.76
(3.91)
6. Secondary Outcome
Title Change in BMI
Description Change from baseline (week 0) in body mass index (BMI) was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 0, Week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 233 239
Mean (Standard Deviation) [Kilograms per square meter (kg/m^2)]
-1.0
(1.5)
-0.3
(1.3)
7. Secondary Outcome
Title Change in Waist Circumference
Description Change from baseline (week 0) in waist circumference was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 0, week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 231 237
Mean (Standard Deviation) [Centimeters (cm)]
-2.6
(5.3)
-0.7
(5.1)
8. Secondary Outcome
Title Change in Total Cholesterol (Ratio to Baseline)
Description Change from baseline (week 0) in total cholesterol (mmol/L) at week 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 0, Week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 226 234
Geometric Mean (Geometric Coefficient of Variation) [Ratio of total cholesterol]
0.96
(19.3)
1.01
(16.2)
9. Secondary Outcome
Title Change in LDL Cholesterol (Ratio to Baseline)
Description Change from baseline (week 0) in low-density lipoprotein (LDL) cholesterol (mmol/L) at week 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 0, week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 226 233
Geometric Mean (Geometric Coefficient of Variation) [Ratio of LDL cholesterol]
0.97
(31.8)
1.03
(27.2)
10. Secondary Outcome
Title Change in HDL Cholesterol (Ratio to Baseline)
Description Change from baseline (week 0) in high-density lipoprotein (HDL) cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 0, week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 226 233
Geometric Mean (Geometric Coefficient of Variation) [Ratio of HDL cholesterol]
1.00
(14.0)
1.02
(16.5)
11. Secondary Outcome
Title Change in Triglycerides (Ratio to Baseline)
Description Change from baseline (week 0) in triglycerides (mmol/L) at week 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 0, week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 226 233
Geometric Mean (Geometric Coefficient of Variation) [Ratio of triglycerides]
0.89
(38.2)
0.91
(43.1)
12. Secondary Outcome
Title Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)
Description SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The 0-100 scale scores (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from baseline (week 0) in the domain scores and component summary (PCS and MCS) scores were evaluated at week 52. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period.
Time Frame Week 0, week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 253 251
Physical functioning
1.54
(7.92)
-0.03
(7.16)
Role physical
0.40
(7.82)
0.13
(8.38)
Bodily pain
1.09
(9.01)
1.20
(8.72)
General health
1.83
(7.65)
1.62
(6.71)
Vitality
1.07
(8.16)
0.51
(7.28)
Social functioning
0.38
(9.00)
0.41
(7.86)
Role emotional
-0.91
(11.71)
-0.54
(10.58)
Mental health
1.21
(8.54)
0.86
(7.97)
PCS
1.51
(6.39)
0.74
(5.81)
MCS
0.01
(8.75)
0.26
(7.67)
13. Secondary Outcome
Title Change in DTSQ
Description Change from baseline (week 0) in diabetes treatment satisfaction questionnaire - status (DTSQs) was evaluated at week 52. The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher scores indicate higher levels of treatment satisfaction for DTSQs items 1, 4 -8. For items 2 and 3 a higher score indicates a higher patient perceived experience of high blood sugars and low blood sugars, respectively. Thus, lower scores indicate a perception of blood glucose levels being "none of the time" unacceptably high (item 2) or low (item 3). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 1, 4-8. The score ranges 0-36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction. Results are based on the data from the in-trial observation period.
Time Frame Week 0, Week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 253 251
1) Satisfaction with treatment
1.09
(1.61)
0.92
(1.65)
2) Feeling of unacceptably high blood sugars
-1.58
(2.13)
-1.14
(2.13)
3) Feeling of unacceptably low blood sugars
-0.15
(1.70)
-0.24
(1.99)
4) Convenience of treatment
0.82
(1.54)
0.59
(1.48)
5) Flexibility of current treatment
0.80
(1.58)
0.68
(1.51)
6) Satisfaction with understanding of diabetes
0.77
(1.51)
0.77
(1.71)
7) Recommending treatment to others
0.88
(1.54)
0.79
(1.46)
8) Satisfaction to continue with present treatment
1.03
(1.66)
0.95
(1.88)
Total treatment satisfaction score
5.39
(6.84)
4.70
(7.23)
14. Secondary Outcome
Title Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol) AACE Target (Yes/no)
Description Participants who achieved HbA1c less than or equal to 6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no) at week 52 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 230 238
Yes
76
30%
29
11.6%
No
154
60.9%
209
83.3%
15. Secondary Outcome
Title Participants Who Achieve Weight Loss ≥5% (Yes/no)
Description Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 52 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 233 239
Yes
63
24.9%
29
11.6%
No
170
67.2%
210
83.7%
16. Secondary Outcome
Title Participants Who Achieve Weight Loss ≥10% (Yes/no)
Description Participants who achieved weight loss more than or equal to 10% of their baseline body weight (yes/no) at week 52 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 233 239
Yes
15
5.9%
5
2%
No
218
86.2%
234
93.2%
17. Secondary Outcome
Title Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)
Description Participants who achieved HbA1c less than 7.0 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) at week 52 is presented. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 230 238
Yes
104
41.1%
35
13.9%
No
126
49.8%
203
80.9%
18. Secondary Outcome
Title Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no)
Description Participants who achieved HbA1c reduction more than or equal to 1% of their baseline HbA1c and weight loss of more than or equal to 3% of their baseline body weight (yes/no) at week 52 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 230 238
Yes
80
31.6%
25
10%
No
150
59.3%
213
84.9%
19. Secondary Outcome
Title Time to Rescue Medication
Description Presented results are the number of participants who had taken rescue medication anytime during the periods, from week 0 to week 52. Rescue medication was defined as any new anti-diabetic medication used as add-on to trial product and used for more than 21 days with the initiation at or after randomisation (week 0) and before last day on trial product, and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before last day on trial product. Results are based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.
Time Frame Weeks 0-52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = FAS which comprised all randomised participants.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 253 251
Count of Participants [Participants]
8
3.2%
40
15.9%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Semaglutide Flex- Main Phase, Sitagliptin 100 mg- Main Phase
Comments Time to initiation of rescue medication was analysed using a Cox proportional hazards model with treatment, strata, and region as categorical fixed effects and baseline HbA1c as covariate. Censoring time was one day before last day on trial product.
Type of Statistical Test Superiority
Comments This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis p-Value <0.0001
Comments Unadjusted two-sided p-value for test of no difference from 1.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.18
Confidence Interval (2-Sided) 95%
0.09 to 0.39
Parameter Dispersion Type:
Value:
Estimation Comments Oral semaglutide flex / Sitagliptin 100 mg
20. Secondary Outcome
Title Time to Additional Anti-diabetic Medication
Description Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the period from week 0 to week 52. Additional anti-diabetic medication was defined as any new anti-diabetic medication used for more than 21 days with the initiation at or after randomisation (week 0) and before (planned) end-of-treatment (week 52), and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before (planned) end-of-treatment. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Weeks 0-52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = FAS which comprised all randomised participants.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 253 251
Count of Participants [Participants]
22
8.7%
47
18.7%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Semaglutide Flex- Main Phase, Sitagliptin 100 mg- Main Phase
Comments Time to initiation of additional anti-diabetic medication was analysed using a Cox proportional hazards model with treatment, strata, and region as categorical fixed effects and baseline HbA1c as covariate. Censoring time was one day before planned end of treatment.
Type of Statistical Test Superiority
Comments This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis p-Value 0.0175
Comments Unadjusted two-sided p-value for test of no difference from 1.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.37 to 0.91
Parameter Dispersion Type:
Value:
Estimation Comments Oral Semaglutide flex / Sitagliptin 100 mg
21. Secondary Outcome
Title Number of TEAEs During Exposure to Trial Product
Description Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 57 (52-week treatment period for participants who continued in the extension phase; 52-week treatment period plus the 5-week follow-up period for participants who did not continue in the extension phase). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period: Time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame Week 0-57

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants who received at least one dose of trial product.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 253 250
Number [Events]
768
519
22. Secondary Outcome
Title Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes
Description Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-57 (52-week treatment period for participants who continued in the extension phase; 52-week treatment period plus the 5-week follow-up period for participants who did not continue in the extension phase). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Time Frame Week 0-57

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 253 250
Number [Episodes]
34
22
23. Secondary Outcome
Title Paticipants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)
Description Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-57 (52-week treatment period for participants who continued in the extension phase; 52-week treatment period plus the 5-week follow-up period for participants who did not continue in the extension phase). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Time Frame Week 0-57

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 253 250
Count of Participants [Participants]
14
5.5%
14
5.6%
24. Secondary Outcome
Title Change in Amylase (Ratio to Baseline)
Description Change from baseline (week 0) in biochemical parameter- amylase (units per liter [U/L]) to week 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame Week 0, Week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 201 225
Geometric Mean (Geometric Coefficient of Variation) [Ratio of amylase]
1.14
(25.5)
1.08
(26.3)
25. Secondary Outcome
Title Change in Lipase (Ratio to Baseline)
Description Change from baseline (week 0) in lipase (U/L) to week 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame Week 0, Week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 201 225
Geometric Mean (Geometric Coefficient of Variation) [Ratio of lipase]
1.24
(55.2)
1.13
(55.3)
26. Secondary Outcome
Title Change in Pulse Rate
Description Change from baseline (week 0) in pulse rate was evaluated at week 52. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame Week 0, week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 206 225
Mean (Standard Deviation) [Beats per minute]
3
(9)
0
(10)
27. Secondary Outcome
Title Change in Blood Pressure (Systolic and Diastolic Blood Pressure)
Description Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at week 52. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame Week 0, week 52

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52).
Measure Participants 206 225
Systolic blood pressure
-3
(14)
-2
(15)
Diastolic blood pressure
-0
(9)
-1
(10)
28. Secondary Outcome
Title Change in HbA1c- Switch
Description Change from week 52 in HbA1c was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 52, week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 92 96
Mean (Standard Deviation) [Percentage of HbA1c]
-0.2
(1.2)
0.0
(1.0)
29. Secondary Outcome
Title Change in Body Weight- Switch
Description Change from week 52 in body weight was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 52, week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 93 97
Mean (Standard Deviation) [Kg]
-2.6
(3.8)
-0.9
(5.4)
30. Secondary Outcome
Title Change in Body Weight (%)- Switch
Description Relative change from week 52 in body weight (kg) was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 52, week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 93 97
Mean (Standard Deviation) [Percentage change]
-3.12
(4.50)
-0.70
(5.27)
31. Secondary Outcome
Title Change in FPG- Switch
Description Change from week 52 in fasting plasma glucose (FPG) was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 52, week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 92 94
Mean (Standard Deviation) [Millimoles per liter (mmol/L)]
-0.35
(1.95)
0.02
(2.31)
32. Secondary Outcome
Title Change in BMI- Switch
Description Change from week 52 in body mass index (BMI) was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 52, Week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 93 97
Mean (Standard Deviation) [kg/m^2]
-0.9
(1.4)
-0.3
(2.2)
33. Secondary Outcome
Title Change in Waist Circumference- Switch
Description Change from week 52 in waist circumference was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 52, week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 93 97
Mean (Standard Deviation) [Centimeters (cm)]
-1.8
(4.3)
-0.9
(5.8)
34. Secondary Outcome
Title Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no)- Switch
Description Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at week 104. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 104 (i.e., after 52 weeks of treatment in the extension phase)

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 92 96
Yes
44
17.4%
26
10.4%
No
48
19%
70
27.9%
35. Secondary Outcome
Title Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol) AACE Target (Yes/no)- Switch
Description Participants who achieved HbA1c less than or equal to 6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no) at week 104 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 104 (i.e., after 52 weeks of treatment in the extension phase)

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 92 96
Yes
28
11.1%
11
4.4%
No
64
25.3%
85
33.9%
36. Secondary Outcome
Title Participants Who Achieve Weight Loss ≥5% (Yes/no)- Switch
Description Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 104 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 104 (i.e., after 52 weeks of treatment in the extension phase)

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 93 97
Yes
31
12.3%
12
4.8%
No
62
24.5%
85
33.9%
37. Secondary Outcome
Title Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)- Switch
Description Participants who achieved HbA1c less than 7.0% without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) at week 104 is presented. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 104 (i.e., after 52 weeks of treatment in the extension phase)

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 92 96
Yes
36
14.2%
18
7.2%
No
56
22.1%
78
31.1%
38. Secondary Outcome
Title Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target and no Need for Rescue Medication (Yes/no)- Switch
Description Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) and no need for rescue medication (yes/no), was evaluated at week 104. Results are based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.
Time Frame Week 104 (i.e., after 52 weeks of treatment in the extension phase)

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 92 96
Count of Participants [Participants]
41
16.2%
23
9.2%
39. Secondary Outcome
Title Time to Additional Anti-diabetic Medication- Switch
Description Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the period from week 53 to week 104. Additional anti-diabetic medication was defined as any new anti-diabetic medication used for more than 21 days with the initiation at or after re-randomisation (week 52) and before (planned) end-of-treatment (week 104), and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before (planned) end-of-treatment. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Weeks 53-104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = FAS which comprised all randomised participants.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 100 98
Count of Participants [Participants]
15
5.9%
26
10.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Semaglutide Flex- Main Phase, Sitagliptin 100 mg- Main Phase
Comments Time to initiation of additional anti-diabetic medication was analysed using a Cox proportional hazards model with treatment, strata, and region as categorical fixed effects and baseline HbA1c as covariate. Censoring time was one day before planned end of treatment.
Type of Statistical Test Superiority
Comments This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis p-Value 0.4381
Comments Unadjusted two-sided p-value for test of no difference from 1.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.39 to 1.50
Parameter Dispersion Type:
Value:
Estimation Comments Oral Semaglutide flex- Switch / Sitagliptin 100 mg- Switch
40. Secondary Outcome
Title Time to Rescue Medication- Switch
Description Presented results are the number of participants who had taken rescue medication anytime during the periods, from week 53 to week 104. Rescue medication was defined as any new anti-diabetic medication used as add-on to trial product and used for more than 21 days with the initiation at or after re-randomisation (week 52) and before last day on trial product, and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before last day on trial product. Results are based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.
Time Frame Weeks 53-104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = FAS which comprised all randomised participants.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 100 98
Count of Participants [Participants]
9
3.6%
23
9.2%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Semaglutide Flex- Main Phase, Sitagliptin 100 mg- Main Phase
Comments Time to initiation of rescue medication was analysed using a Cox proportional hazards model with treatment, strata, and region as categorical fixed effects and baseline HbA1c as covariate. Censoring time was one day before last day on trial product.
Type of Statistical Test Superiority
Comments This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis p-Value 0.0790
Comments Unadjusted two-sided p-value for test of no difference from 1.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.20 to 1.09
Parameter Dispersion Type:
Value:
Estimation Comments Oral semaglutide flex- Switch / Sitagliptin 100 mg- Switch
41. Secondary Outcome
Title Number of TEAEs During Exposure to Trial Product- Switch
Description Treatment emergent adverse events (TEAEs) were recorded from week 53 to week 109. Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period: Time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame Week 53-109

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants who received at least one dose of trial product.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 100 97
Number [Events]
267
225
42. Secondary Outcome
Title Change in Amylase (Ratio to Baseline)- Switch
Description Change from week 52 in biochemical parameter- amylase (U/L) to week 104 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame Week 52, Week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 84 92
Geometric Mean (Geometric Coefficient of Variation) [Ratio of amylase]
1.09
(22.9)
1.00
(26.6)
43. Secondary Outcome
Title Change in Lipase (Ratio to Baseline)- Switch
Description Change from week 52 in lipase (U/L) to week 104 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame Week 52, Week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 84 92
Geometric Mean (Geometric Coefficient of Variation) [Ratio of lipase]
1.13
(46.7)
0.92
(54.9)
44. Secondary Outcome
Title Change in Pulse Rate- Switch
Description Change from week 52 in pulse rate was evaluated at week 104. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame Week 52, week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 87 93
Mean (Standard Deviation) [Beats per minute]
1
(9)
-0
(10)
45. Secondary Outcome
Title Change in Blood Pressure (Systolic and Diastolic Blood Pressure)- Switch
Description Change from week 52 in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at week 104. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame Week 52, week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 87 93
Systolic blood pressure
-3
(15)
2
(15)
Diastolic blood pressure
-1
(10)
-0
(10)
46. Secondary Outcome
Title Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes- Switch
Description Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 53 to 109. Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Time Frame Week 53-109

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 100 97
Number [Episodes]
2
12
47. Secondary Outcome
Title Paticipants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)- Switch
Description Number of participants with treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 53 to 109. Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Time Frame Week 53-109

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 100 97
Count of Participants [Participants]
2
0.8%
4
1.6%
48. Secondary Outcome
Title Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)- Switch
Description SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The 0-100 scale scores (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from week 52 in the domain scores and component summary (PCS and MCS) scores were evaluated at week 104. A positive change score indicates an improvement since week 52. Results are based on the data from the in-trial observation period.
Time Frame Week 52, week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 93 97
Physical functioning
1.14
(8.55)
-0.97
(6.71)
Role physical
1.37
(7.68)
-0.22
(7.61)
Bodily pain
-0.18
(7.22)
-0.30
(7.06)
General health
0.69
(6.74)
0.53
(6.59)
Vitality
-0.18
(6.91)
-0.15
(7.32)
Social functioning
0.21
(7.36)
0.10
(6.54)
Role emotional
1.72
(9.61)
-0.39
(8.79)
Mental health
0.37
(6.68)
0.20
(6.46)
PCS
0.66
(6.06)
-0.43
(5.36)
MCS
0.52
(7.21)
0.19
(6.46)
49. Secondary Outcome
Title Change in DTSQ- Switch
Description Change from week 52 in diabetes treatment satisfaction questionnaire - status (DTSQs) was evaluated at week 104. The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher scores indicate higher levels of treatment satisfaction for DTSQs items 1, 4 -8. For items 2 and 3 a higher score indicates a higher patient perceived experience of high blood sugars and low blood sugars, respectively. Thus, lower scores indicate a perception of blood glucose levels being "none of the time" unacceptably high (item 2) or low (item 3). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 1, 4-8. The score ranges 0-36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction. Results are based on the data from the in-trial observation period.
Time Frame Week 52, week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
Measure Participants 100 98
1) Satisfaction with treatment
0.06
(1.06)
-0.24
(1.43)
2) Feeling of unacceptably high blood sugars
-0.32
(1.95)
0.09
(2.04)
3) Feeling of unacceptably low blood sugars
0.02
(1.63)
0.23
(1.94)
4) Convenience of treatment
0.13
(1.18)
0.13
(1.16)
5) Flexibility of current treatment
0.01
(1.19)
0.06
(1.22)
6) Satisfaction with understanding of diabetes
0.02
(1.38)
0.04
(1.16)
7) Recommending treatment to others
0.04
(1.04)
-0.05
(1.20)
8) Satisfaction to continue with present treatment
-0.05
(1.07)
0.00
(1.48)
Total treatment satisfaction score
0.20
(5.14)
-0.06
(5.62)
50. Secondary Outcome
Title Change in HbA1c- Sustainability
Description Change from baseline (week 0) in HbA1c was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 0, week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Sustainability
Arm/Group Description Participants were to receive oral semaglutide tablets once daily for 104 weeks (week 0-52 in the main phase and week 53-104 in the extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 104).
Measure Participants 180
Mean (Standard Deviation) [Percentage of HbA1c]
-1.3
(1.0)
51. Secondary Outcome
Title Change in Body Weight (kg)- Sustainability
Description Change from baseline (week 0) in body weight was evaluated at week 104. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 0, week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Sustainability
Arm/Group Description Participants were to receive oral semaglutide tablets once daily for 104 weeks (week 0-52 in the main phase and week 53-104 in the extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 104).
Measure Participants 180
Mean (Standard Deviation) [Kg]
-3.7
(5.2)
52. Secondary Outcome
Title Change in Body Weight (%)- Sustainability
Description Relative change from baseline (week 0) in body weight (kg) was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 0, week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Sustainability
Arm/Group Description Participants were to receive oral semaglutide tablets once daily for 104 weeks (week 0-52 in the main phase and week 53-104 in the extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 104).
Measure Participants 180
Mean (Standard Deviation) [Percentage change]
-4.03
(5.75)
53. Secondary Outcome
Title Change in FPG- Sustainability
Description Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 0, week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Sustainability
Arm/Group Description Participants were to receive oral semaglutide tablets once daily for 104 weeks (week 0-52 in the main phase and week 53-104 in the extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 104).
Measure Participants 178
Mean (Standard Deviation) [Millimoles per liter (mmol/L)]
-39.4
(51.2)
54. Secondary Outcome
Title Change in BMI- Sustainability
Description Change from baseline (week 0) in body mass index (BMI) was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 0, Week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Sustainability
Arm/Group Description Participants were to receive oral semaglutide tablets once daily for 104 weeks (week 0-52 in the main phase and week 53-104 in the extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 104).
Measure Participants 180
Mean (Standard Deviation) [kg/m^2]
-1.3
(1.9)
55. Secondary Outcome
Title Change in Waist Circumference- Sustainability
Description Change from baseline (week 0) in waist circumference was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 0, week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Sustainability
Arm/Group Description Participants were to receive oral semaglutide tablets once daily for 104 weeks (week 0-52 in the main phase and week 53-104 in the extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 104).
Measure Participants 178
Mean (Standard Deviation) [cm]
-2.5
(6.3)
56. Secondary Outcome
Title Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no)- Sustainability
Description Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at week 104. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Sustainability
Arm/Group Description Participants were to receive oral semaglutide tablets once daily for 104 weeks (week 0-52 in the main phase and week 53-104 in the extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 104).
Measure Participants 180
Yes
101
39.9%
No
79
31.2%
57. Secondary Outcome
Title Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol) AACE Target (Yes/no)- Sustainability
Description Participants who achieved HbA1c less than or equal to 6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no) at week 104 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Sustainability
Arm/Group Description Participants were to receive oral semaglutide tablets once daily for 104 weeks (week 0-52 in the main phase and week 53-104 in the extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 104).
Measure Participants 180
Yes
63
24.9%
No
117
46.2%
58. Secondary Outcome
Title Participants Who Achieve Weight Loss ≥5% (Yes/no)- Sustainability
Description Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 104 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Sustainability
Arm/Group Description Participants were to receive oral semaglutide tablets once daily for 104 weeks (week 0-52 in the main phase and week 53-104 in the extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 104).
Measure Participants 180
Yes
61
24.1%
No
119
47%
59. Secondary Outcome
Title Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)- Sustainability
Description Participants who achieved HbA1c less than 7.0 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) at week 104 is presented. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Sustainability
Arm/Group Description Participants were to receive oral semaglutide tablets once daily for 104 weeks (week 0-52 in the main phase and week 53-104 in the extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 104).
Measure Participants 180
Yes
73
28.9%
No
107
42.3%
60. Secondary Outcome
Title Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target or HbA1c Reduction ≥ 1%-Point (10.9 mmol/Mol) (Yes/no)- Sustainability
Description Participants who achieved HbA1c <7.0% ADA target or HbA1c reduction ≥ 1%-point (10.9 mmol/mol) (yes/no), was evaluated at week 104. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame Week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Sustainability
Arm/Group Description Participants were to receive oral semaglutide tablets once daily for 104 weeks (week 0-52 in the main phase and week 53-104 in the extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 104).
Measure Participants 180
Yes
126
49.8%
No
54
21.3%
61. Secondary Outcome
Title Number of TEAEs During Exposure to Trial Product- Sustainability
Description Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 109 ((104-week treatment period for participants who continued in the extension phase or 52-week treatment period for participants who did not continue in the extension phase) plus the 5-week follow-up period). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period: Time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame Week 0-109

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product.
Arm/Group Title Oral Semaglutide Flex- Sustainability
Arm/Group Description Participants were to receive oral semaglutide tablets once daily for 104 weeks (week 0-52 in the main phase and week 53-104 in the extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 104).
Measure Participants 253
Number [Events]
1157
62. Secondary Outcome
Title Change in Amylase (Ratio to Baseline)- Sustainability
Description Change from baseline (week 0) in biochemical parameter- amylase (units per liter [U/L]) to week 104 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame Week 0, week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Sustainability
Arm/Group Description Participants were to receive oral semaglutide tablets once daily for 104 weeks (week 0-52 in the main phase and week 53-104 in the extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 104).
Measure Participants 167
Geometric Mean (Geometric Coefficient of Variation) [Ratio of amylase]
1.13
(25.1)
63. Secondary Outcome
Title Change in Lipase (Ratio to Baseline)- Sustainability
Description Change from baseline (week 0) in lipase (U/L) to week 104 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame Week 0, Week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Sustainability
Arm/Group Description Participants were to receive oral semaglutide tablets once daily for 104 weeks (week 0-52 in the main phase and week 53-104 in the extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 104).
Measure Participants 167
Geometric Mean (Geometric Coefficient of Variation) [Ratio of lipase]
1.18
(58.0)
64. Secondary Outcome
Title Change in Pulse Rate- Sustainability
Description Change from baseline (week 0) in pulse rate was evaluated at week 104. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame Week 0, week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Sustainability
Arm/Group Description Participants were to receive oral semaglutide tablets once daily for 104 weeks (week 0-52 in the main phase and week 53-104 in the extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 104).
Measure Participants 176
Mean (Standard Deviation) [Beats per minute]
2
(9)
65. Secondary Outcome
Title Change in Blood Pressure (Systolic and Diastolic Blood Pressure)- Sustainability
Description Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at week 104. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame Week 0, week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Sustainability
Arm/Group Description Participants were to receive oral semaglutide tablets once daily for 104 weeks (week 0-52 in the main phase and week 53-104 in the extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 104).
Measure Participants 176
Systolic blood pressure
-3
(14)
Diastolic blood pressure
-1
(9)
66. Secondary Outcome
Title Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes)- Sustainability
Description Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-109 ((104-week treatment period for participants who continued in the extension phase or 52-week treatment period for participants who did not continue in the extension phase) plus the 5-week follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Time Frame Week 0-109

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product.
Arm/Group Title Oral Semaglutide Flex- Sustainability
Arm/Group Description Participants were to receive oral semaglutide tablets once daily for 104 weeks (week 0-52 in the main phase and week 53-104 in the extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 104).
Measure Participants 253
Number [Episodes]
45
67. Secondary Outcome
Title Paticipants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)- Sustainability
Description Number of participants with treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-109 ((104-week treatment period for participants who continued in the extension phase or 52-week treatment period for participants who did not continue in the extension phase) plus the 5-week follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Time Frame Week 0-109

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product.
Arm/Group Title Oral Semaglutide Flex- Sustainability
Arm/Group Description Participants were to receive oral semaglutide tablets once daily for 104 weeks (week 0-52 in the main phase and week 53-104 in the extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 104).
Measure Participants 253
Count of Participants [Participants]
18
7.1%
68. Secondary Outcome
Title Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)- Sustainability
Description Short form (SF)-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The 0-100 scale scores (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from baseline (week 0) in the domain scores and component summary (PCS and MCS) scores were evaluated at week 104. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period.
Time Frame Week 0, week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Sustainability
Arm/Group Description Participants were to receive oral semaglutide tablets once daily for 104 weeks (week 0-52 in the main phase and week 53-104 in the extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 104).
Measure Participants 180
Physical functioning
1.44
(8.48)
Role physical
0.22
(8.31)
Bodily pain
1.07
(9.72)
General health
1.98
(8.01)
Vitality
0.97
(8.49)
Social functioning
-0.11
(8.14)
Role emotional
-0.04
(10.49)
Mental health
1.05
(8.25)
PCS
1.33
(6.96)
MCS
0.20
(8.34)
69. Secondary Outcome
Title Change in DTSQ- Sustainability
Description Change from week 0 in diabetes treatment satisfaction questionnaire - status (DTSQs) was evaluated at week 104. The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher scores indicate higher levels of treatment satisfaction for DTSQs items 1, 4 -8. For items 2 and 3 a higher score indicates a higher patient perceived experience of high blood sugars and low blood sugars, respectively. Thus, lower scores indicate a perception of blood glucose levels being "none of the time" unacceptably high (item 2) or low (item 3). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 1, 4-8. The score ranges 0-36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction. Results are based on the data from the in-trial observation period.
Time Frame Week 0, week 104

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.
Arm/Group Title Oral Semaglutide Flex- Sustainability
Arm/Group Description Participants were to receive oral semaglutide tablets once daily for 104 weeks (week 0-52 in the main phase and week 53-104 in the extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 104).
Measure Participants 180
1) Satisfaction with treatment
1.19
(1.61)
2) Feeling of unacceptably high blood sugars
-1.46
(2.44)
3) Feeling of unacceptably low blood sugars
-0.14
(2.09)
4) Convenience of treatment
0.88
(1.52)
5) Flexibility of current treatment
0.86
(1.56)
6) Satisfaction with understanding of diabetes
0.84
(1.50)
7) Recommending treatment to others
0.94
(1.58)
8) Satisfaction to continue with present treatment
1.11
(1.62)
Total treatment satisfaction score
5.81
(7.11)

Adverse Events

Time Frame Week 0 to week 109. Results are based on the safety analysis set (SAS), which comprised all randomised participants who received at least one dose of trial product.
Adverse Event Reporting Description Serious adverse events and other AEs were based on the on-treatment observation period, i.e., the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. All-cause mortality were based on the in-trial observation period, i.e., the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Arm/Group Title Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase Oral Semaglutide Flex- Sustainability Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Arm/Group Description Participants were to receive oral semaglutide tablets once daily from week 0 to week 52 (main phase): 3 milligrams (mg) for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive 100 mg sitagliptin tablet once daily for 52 weeks (main phase). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 52). Participants were to receive oral semaglutide tablets once daily for 104 weeks (week 0-52 in the main phase and week 53-104 in the extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 0 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to receive oral semaglutide tablets once daily from week 53 to week 104 (extension phase): 3 mg for the first 8 weeks, 3 or 7 mg for next 8 weeks followed by 3, 7 or 14 mg for the remaining treatment period. Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104). Participants who were still on sitagliptin 100 mg treatment at week 52 (end of main phase) were re-randomised to continue sitagliptin in the extension phase (week 53 to week 104). Participants were to continue their anti-diabetic background medication (metformin, sulphonylurea, thiazolidinedione or sodium-glucose co-transporter 2 inhibitors) throughout the trial (week 53 to week 104).
All Cause Mortality
Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase Oral Semaglutide Flex- Sustainability Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/253 (0%) 2/250 (0.8%) 0/253 (0%) 0/100 (0%) 0/97 (0%)
Serious Adverse Events
Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase Oral Semaglutide Flex- Sustainability Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 24/253 (9.5%) 24/250 (9.6%) 36/253 (14.2%) 9/100 (9%) 7/97 (7.2%)
Cardiac disorders
Acute myocardial infarction 0/253 (0%) 0 2/250 (0.8%) 2 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Angina unstable 1/253 (0.4%) 1 0/250 (0%) 0 2/253 (0.8%) 3 1/100 (1%) 1 0/97 (0%) 0
Cardiac failure chronic 0/253 (0%) 0 1/250 (0.4%) 1 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Coronary artery disease 0/253 (0%) 0 1/250 (0.4%) 1 2/253 (0.8%) 4 0/100 (0%) 0 0/97 (0%) 0
Coronary artery insufficiency 1/253 (0.4%) 1 0/250 (0%) 0 1/253 (0.4%) 1 0/100 (0%) 0 0/97 (0%) 0
Myocardial ischaemia 0/253 (0%) 0 1/250 (0.4%) 1 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Atrial fibrillation 0/253 (0%) 0 0/250 (0%) 0 0/253 (0%) 0 1/100 (1%) 1 0/97 (0%) 0
Cardiac failure congestive 0/253 (0%) 0 0/250 (0%) 0 0/253 (0%) 0 1/100 (1%) 1 1/97 (1%) 2
Ear and labyrinth disorders
Otosclerosis 0/253 (0%) 0 0/250 (0%) 0 0/253 (0%) 0 1/100 (1%) 1 0/97 (0%) 0
Eye disorders
Cataract 1/253 (0.4%) 1 0/250 (0%) 0 1/253 (0.4%) 1 0/100 (0%) 0 1/97 (1%) 1
Macular fibrosis 0/253 (0%) 0 0/250 (0%) 0 0/253 (0%) 0 1/100 (1%) 1 0/97 (0%) 0
Gastrointestinal disorders
Gastric ulcer 0/253 (0%) 0 1/250 (0.4%) 1 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Ileus 0/253 (0%) 0 1/250 (0.4%) 1 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Inguinal hernia 0/253 (0%) 0 1/250 (0.4%) 1 0/253 (0%) 0 1/100 (1%) 1 0/97 (0%) 0
Intestinal mass 1/253 (0.4%) 1 0/250 (0%) 0 1/253 (0.4%) 1 0/100 (0%) 0 0/97 (0%) 0
Irritable bowel syndrome 0/253 (0%) 0 1/250 (0.4%) 1 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Abdominal pain 0/253 (0%) 0 0/250 (0%) 0 0/253 (0%) 0 0/100 (0%) 0 1/97 (1%) 1
Diarrhoea 0/253 (0%) 0 0/250 (0%) 0 0/253 (0%) 0 1/100 (1%) 1 0/97 (0%) 0
Gastrointestinal inflammation 0/253 (0%) 0 0/250 (0%) 0 1/253 (0.4%) 2 0/100 (0%) 0 0/97 (0%) 0
Hiatus hernia 0/253 (0%) 0 0/250 (0%) 0 0/253 (0%) 0 0/100 (0%) 0 1/97 (1%) 1
Nausea 0/253 (0%) 0 0/250 (0%) 0 0/253 (0%) 0 0/100 (0%) 0 1/97 (1%) 1
General disorders
Malaise 1/253 (0.4%) 1 0/250 (0%) 0 1/253 (0.4%) 1 0/100 (0%) 0 0/97 (0%) 0
Non-cardiac chest pain 0/253 (0%) 0 1/250 (0.4%) 1 1/253 (0.4%) 2 0/100 (0%) 0 1/97 (1%) 1
Pain 0/253 (0%) 0 1/250 (0.4%) 1 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Pyrexia 1/253 (0.4%) 1 0/250 (0%) 0 1/253 (0.4%) 1 0/100 (0%) 0 0/97 (0%) 0
Hepatobiliary disorders
Cholecystitis acute 0/253 (0%) 0 1/250 (0.4%) 1 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Infections and infestations
Campylobacter gastroenteritis 1/253 (0.4%) 1 0/250 (0%) 0 1/253 (0.4%) 1 0/100 (0%) 0 0/97 (0%) 0
Escherichia pyelonephritis 0/253 (0%) 0 1/250 (0.4%) 1 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Pyelonephritis 1/253 (0.4%) 1 0/250 (0%) 0 1/253 (0.4%) 1 0/100 (0%) 0 0/97 (0%) 0
Streptococcal sepsis 0/253 (0%) 0 1/250 (0.4%) 1 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Ophthalmic herpes zoster 0/253 (0%) 0 0/250 (0%) 0 0/253 (0%) 0 0/100 (0%) 0 1/97 (1%) 1
Otitis media chronic 0/253 (0%) 0 0/250 (0%) 0 0/253 (0%) 0 0/100 (0%) 0 1/97 (1%) 1
Injury, poisoning and procedural complications
Fall 2/253 (0.8%) 2 0/250 (0%) 0 2/253 (0.8%) 2 0/100 (0%) 0 0/97 (0%) 0
Femur fracture 1/253 (0.4%) 1 0/250 (0%) 0 1/253 (0.4%) 1 0/100 (0%) 0 0/97 (0%) 0
Hip fracture 1/253 (0.4%) 1 0/250 (0%) 0 1/253 (0.4%) 1 0/100 (0%) 0 0/97 (0%) 0
Road traffic accident 0/253 (0%) 0 1/250 (0.4%) 1 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Joint dislocation 0/253 (0%) 0 0/250 (0%) 0 0/253 (0%) 0 1/100 (1%) 1 0/97 (0%) 0
Joint injury 0/253 (0%) 0 0/250 (0%) 0 0/253 (0%) 0 1/100 (1%) 1 0/97 (0%) 0
Laceration 0/253 (0%) 0 0/250 (0%) 0 0/253 (0%) 0 0/100 (0%) 0 1/97 (1%) 1
Investigations
Catheterisation cardiac 0/253 (0%) 0 1/250 (0.4%) 1 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Metabolism and nutrition disorders
Hyperglycaemia 1/253 (0.4%) 1 0/250 (0%) 0 1/253 (0.4%) 1 0/100 (0%) 0 0/97 (0%) 0
Musculoskeletal and connective tissue disorders
Arthritis 0/253 (0%) 0 1/250 (0.4%) 1 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Musculoskeletal chest pain 0/253 (0%) 0 1/250 (0.4%) 1 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Bursitis 0/253 (0%) 0 0/250 (0%) 0 0/253 (0%) 0 1/100 (1%) 1 0/97 (0%) 0
Osteoarthritis 0/253 (0%) 0 0/250 (0%) 0 3/253 (1.2%) 4 0/100 (0%) 0 0/97 (0%) 0
Rhabdomyolysis 0/253 (0%) 0 0/250 (0%) 0 0/253 (0%) 0 1/100 (1%) 1 0/97 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma gastric 1/253 (0.4%) 1 0/250 (0%) 0 1/253 (0.4%) 1 0/100 (0%) 0 0/97 (0%) 0
Adenocarcinoma of colon 2/253 (0.8%) 2 0/250 (0%) 0 2/253 (0.8%) 2 0/100 (0%) 0 0/97 (0%) 0
Basal cell carcinoma 0/253 (0%) 0 1/250 (0.4%) 1 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Choroid melanoma 1/253 (0.4%) 1 0/250 (0%) 0 1/253 (0.4%) 1 0/100 (0%) 0 0/97 (0%) 0
Hepatocellular carcinoma 1/253 (0.4%) 1 0/250 (0%) 0 1/253 (0.4%) 1 0/100 (0%) 0 0/97 (0%) 0
Intraductal papillary mucinous neoplasm 1/253 (0.4%) 1 0/250 (0%) 0 1/253 (0.4%) 1 0/100 (0%) 0 0/97 (0%) 0
Invasive ductal breast carcinoma 1/253 (0.4%) 1 1/250 (0.4%) 1 2/253 (0.8%) 3 0/100 (0%) 0 0/97 (0%) 0
Prostate cancer 1/253 (0.4%) 1 0/250 (0%) 0 1/253 (0.4%) 1 0/100 (0%) 0 0/97 (0%) 0
Uterine leiomyoma 1/253 (0.4%) 1 1/250 (0.4%) 1 1/253 (0.4%) 1 0/100 (0%) 0 0/97 (0%) 0
Clear cell renal cell carcinoma 0/253 (0%) 0 0/250 (0%) 0 0/253 (0%) 0 1/100 (1%) 1 0/97 (0%) 0
Endometrial adenocarcinoma 0/253 (0%) 0 0/250 (0%) 0 1/253 (0.4%) 2 0/100 (0%) 0 0/97 (0%) 0
Lung cancer metastatic 0/253 (0%) 0 0/250 (0%) 0 0/253 (0%) 0 1/100 (1%) 1 0/97 (0%) 0
Malignant melanoma 0/253 (0%) 0 0/250 (0%) 0 1/253 (0.4%) 2 0/100 (0%) 0 0/97 (0%) 0
Ovarian endometrioid carcinoma 0/253 (0%) 0 0/250 (0%) 0 1/253 (0.4%) 2 0/100 (0%) 0 0/97 (0%) 0
Nervous system disorders
Ischaemic stroke 0/253 (0%) 0 1/250 (0.4%) 1 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Dizziness 0/253 (0%) 0 0/250 (0%) 0 0/253 (0%) 0 0/100 (0%) 0 1/97 (1%) 1
Myelopathy 0/253 (0%) 0 0/250 (0%) 0 0/253 (0%) 0 0/100 (0%) 0 1/97 (1%) 1
Psychiatric disorders
Depression 1/253 (0.4%) 1 0/250 (0%) 0 1/253 (0.4%) 1 0/100 (0%) 0 0/97 (0%) 0
Nightmare 0/253 (0%) 0 1/250 (0.4%) 1 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Renal and urinary disorders
Bladder prolapse 1/253 (0.4%) 1 0/250 (0%) 0 1/253 (0.4%) 1 0/100 (0%) 0 0/97 (0%) 0
Renal colic 2/253 (0.8%) 2 1/250 (0.4%) 1 2/253 (0.8%) 2 0/100 (0%) 0 0/97 (0%) 0
Ureterolithiasis 0/253 (0%) 0 1/250 (0.4%) 1 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Acute kidney injury 0/253 (0%) 0 0/250 (0%) 0 1/253 (0.4%) 2 0/100 (0%) 0 0/97 (0%) 0
Reproductive system and breast disorders
Benign prostatic hyperplasia 0/253 (0%) 0 2/250 (0.8%) 2 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema 0/253 (0%) 0 1/250 (0.4%) 1 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Cough 1/253 (0.4%) 1 0/250 (0%) 0 1/253 (0.4%) 1 0/100 (0%) 0 0/97 (0%) 0
Emphysema 0/253 (0%) 0 0/250 (0%) 0 0/253 (0%) 0 0/100 (0%) 0 1/97 (1%) 1
Pharyngeal polyp 0/253 (0%) 0 0/250 (0%) 0 1/253 (0.4%) 2 0/100 (0%) 0 0/97 (0%) 0
Skin and subcutaneous tissue disorders
Hidradenitis 0/253 (0%) 0 1/250 (0.4%) 1 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Surgical and medical procedures
Cataract operation 0/253 (0%) 0 0/250 (0%) 0 1/253 (0.4%) 2 0/100 (0%) 0 0/97 (0%) 0
Gastric bypass 0/253 (0%) 0 0/250 (0%) 0 0/253 (0%) 0 0/100 (0%) 0 1/97 (1%) 1
Shoulder operation 0/253 (0%) 0 0/250 (0%) 0 1/253 (0.4%) 2 0/100 (0%) 0 0/97 (0%) 0
Vascular disorders
Aortic stenosis 1/253 (0.4%) 1 0/250 (0%) 0 1/253 (0.4%) 1 0/100 (0%) 0 0/97 (0%) 0
Peripheral artery stenosis 0/253 (0%) 0 1/250 (0.4%) 1 0/253 (0%) 0 0/100 (0%) 0 0/97 (0%) 0
Other (Not Including Serious) Adverse Events
Oral Semaglutide Flex- Main Phase Sitagliptin 100 mg- Main Phase Oral Semaglutide Flex- Sustainability Oral Semaglutide Flex- Switch Sitagliptin 100 mg- Switch
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 126/253 (49.8%) 70/250 (28%) 148/253 (58.5%) 46/100 (46%) 27/97 (27.8%)
Gastrointestinal disorders
Abdominal pain upper 16/253 (6.3%) 17 3/250 (1.2%) 3 20/253 (7.9%) 27 6/100 (6%) 6 1/97 (1%) 2
Diarrhoea 22/253 (8.7%) 25 8/250 (3.2%) 11 29/253 (11.5%) 39 10/100 (10%) 11 3/97 (3.1%) 5
Dyspepsia 13/253 (5.1%) 13 2/250 (0.8%) 4 18/253 (7.1%) 23 4/100 (4%) 4 2/97 (2.1%) 2
Nausea 53/253 (20.9%) 83 6/250 (2.4%) 8 58/253 (22.9%) 113 17/100 (17%) 19 3/97 (3.1%) 3
Vomiting 14/253 (5.5%) 21 2/250 (0.8%) 2 18/253 (7.1%) 39 7/100 (7%) 8 2/97 (2.1%) 2
Constipation 7/253 (2.8%) 9 7/250 (2.8%) 8 11/253 (4.3%) 17 5/100 (5%) 5 1/97 (1%) 1
Infections and infestations
Nasopharyngitis 26/253 (10.3%) 30 13/250 (5.2%) 15 34/253 (13.4%) 58 7/100 (7%) 8 10/97 (10.3%) 11
Upper respiratory tract infection 9/253 (3.6%) 9 15/250 (6%) 16 18/253 (7.1%) 33 1/100 (1%) 2 4/97 (4.1%) 5
Gastroenteritis 9/253 (3.6%) 9 1/250 (0.4%) 1 13/253 (5.1%) 19 3/100 (3%) 3 0/97 (0%) 0
Influenza 10/253 (4%) 11 6/250 (2.4%) 8 15/253 (5.9%) 23 6/100 (6%) 6 4/97 (4.1%) 5
Musculoskeletal and connective tissue disorders
Arthralgia 8/253 (3.2%) 12 8/250 (3.2%) 9 17/253 (6.7%) 34 3/100 (3%) 5 4/97 (4.1%) 4
Back pain 9/253 (3.6%) 14 11/250 (4.4%) 14 17/253 (6.7%) 34 3/100 (3%) 3 5/97 (5.2%) 5
Nervous system disorders
Headache 25/253 (9.9%) 33 15/250 (6%) 15 29/253 (11.5%) 47 4/100 (4%) 4 3/97 (3.1%) 3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.

Results Point of Contact

Name/Title Clinical Reporting Anchor and Disclosure (1452)
Organization Novo Nordisk A/S
Phone (+1) 866-867-7178
Email clinicaltrials@novonordisk.com
Responsible Party:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT02849080
Other Study ID Numbers:
  • NN9924-4257
  • 2015-005593-38
  • U1111-1177-5103
First Posted:
Jul 29, 2016
Last Update Posted:
Jul 20, 2022
Last Verified:
Jul 1, 2022