onset 9: Research Study Comparing a New Medicine "Fast-acting Insulin Aspart" to Another Already Available Medicine "NovoRapid"/"NovoLog" in People With Type 2 Diabetes

Sponsor
Novo Nordisk A/S (Industry)
Overall Status
Completed
CT.gov ID
NCT03268005
Collaborator
(none)
1,264
167
2
16.3
7.6
0.5

Study Details

Study Description

Brief Summary

The study compares 2 medicines for type 2 diabetes: fast-acting insulin aspart (a new medicine) and NovoRapid®/NovoLog® (a medicine doctors can already prescribe). Fast-acting insulin aspart will be tested to see how well it works and if it is safe. Participants will get either fast-acting insulin aspart or NovoRapid®/ NovoLog® - which treatment you get is decided by chance. Both medicines will be taken together with insulin degludec. Participants will need to take 1 injection 4 times every day (all insulins will be provided in pens). The study will last for about 8 months (34 weeks).

Condition or Disease Intervention/Treatment Phase
  • Drug: Faster-acting insulin aspart
  • Drug: Insulin aspart
  • Drug: Insulin degludec
  • Drug: Metformin
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
1264 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Sponsor staff involved in the clinical trial is masked according to company standard procedures.
Primary Purpose:
Treatment
Official Title:
Efficacy and Safety of Fast-acting Insulin Aspart Compared to NovoRapid® Both in Combination With Insulin Degludec With or Without Metformin in Adults With Type 2 Diabetes (Onset® 9)
Actual Study Start Date :
Sep 19, 2017
Actual Primary Completion Date :
Jan 7, 2019
Actual Study Completion Date :
Jan 29, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Faster aspart + insulin degludec with or without metformin

Drug: Faster-acting insulin aspart
Faster aspart given subcutaneously (s.c., under the skin) once a day for 16 weeks. Dose individually adjusted.

Drug: Insulin degludec
Insulin degludec given subcutaneously (s.c., under the skin) once a day for 16 weeks. Dose individually adjusted.

Drug: Metformin
Only participants who took metformin before the study should take metformin tablets, same dose as before the study

Active Comparator: NovoRapid/NovoLog + insulin degludec with or without metformin

Drug: Insulin aspart
Insulin aspart given subcutaneously (s.c., under the skin) once a day for 16 weeks. Dose individually adjusted.

Drug: Insulin degludec
Insulin degludec given subcutaneously (s.c., under the skin) once a day for 16 weeks. Dose individually adjusted.

Drug: Metformin
Only participants who took metformin before the study should take metformin tablets, same dose as before the study

Outcome Measures

Primary Outcome Measures

  1. Change in Glycosylated Haemoglobin (HbA1c) [Week 0, week 16]

    Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 16. The endpoint was evaluated based on data from the in-trial observation period. In-trial observation period was from date of randomisation and until last trial-related participant-site contact.

Secondary Outcome Measures

  1. Change From Baseline in 1-hour PPG Increment [Week 0, week 16]

    Change from baseline (week 0) in 1-hour postprandial glucose (PPG) increment was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

  2. Change From Baseline in 1,5-anhydroglucitol [Week 0, week 16]

    Change from baseline (week 0) in 1,5-anhydroglucitol was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

  3. Change From Baseline in Fasting Plasma Glucose (FPG) [Week 0, week 16]

    Change from baseline (week 0) in fasting plasma glucose was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

  4. Participants Who Achieved HbA1c <7.0% (53 mmol/L) (Yes/No) [16 weeks after randomisation]

    Number of participants reaching HbA1c <7.0% (53 mmol/L) was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

  5. Participants Who Achieved HbA1c <7.0% (53 mmol/L) Without Severe Hypoglycaemia Episodes (Yes/No) [16 weeks after randomisation]

    Number of participants reaching HbA1c <7.0% (53 mmol/L) without severe hypoglycaemia episodes was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

  6. Change From Baseline (Week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour Postprandial Glucose (PPG [Meal Test]) [Week 0, week 16]

    Change from baseline (week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour postprandial glucose (PPG [meal test]) was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact. Meal test: The subjects were given a carbohydrate-rich standardised liquid meal immediately after bolus (faster aspart or NovoRapid) infusion in the morning of the meal test. The subjects were to consume the meal as quickly as possible (within 12 minutes) and blood samples were drawn after 30 minutes, 1, 2, 3 and 4 hours from the start of the meal.

  7. Change From Baseline (Week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour PPG Increment (Meal Test) [Week 0, week 16]

    Change from baseline (week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour PPG increment (meal test) was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact. Meal test: The subjects were given a carbohydrate-rich standardised liquid meal immediately after bolus (faster aspart or NovoRapid) infusion in the morning of the meal test. The subjects were to consume the meal as quickly as possible (within 12 minutes) and blood samples were drawn after 30 minutes, 1, 2, 3 and 4 hours from the start of the meal. PPG incremental value for each time point was derived as PPG value at that time point minus the preprandial glucose value.

  8. Change From Baseline in Mean of the 7-9-7 Point Self-measured Plasma Glucose (SMPG) Profile [Week 0, week 16]

    Change from baseline (week 0) in mean of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. 7-9-7 point SMPG was measured at the following mentioned time points: 1) Before breakfast, 2) 60 mins after the start of Breakfast, 3) Before lunch, 4) 60 mins after the start of lunch, 5) Before main evening meal, 6) 60 mins after the start of main evening meal, 7) At bedtime, 8) At 4 AM, 9) Before breakfast.

  9. Change From Baseline of the 7-9-7 Point SMPG Profile: PPG (Mean, Breakfast, Lunch and Main Evening Meal) [Week 0, week 16]

    Change from baseline (week 0) in PPG (breakfast, lunch, main evening meal and mean over all meals) of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

  10. Change From Baseline of the 7-9-7 Point SMPG Profile: PPG Increment (Mean, Breakfast, Lunch and Main Evening Meal) [Week 0, week 16]

    Change from baseline (week 0) in PPG increment (breakfast, lunch, main evening meal and mean over all meals) of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. PPG increment based on the 7-9-7-point profiles were derived separately for PG measurements made at 1 hour after main meals (breakfast, lunch and main evening meal). PPG incremental value for each time point was derived as PPG value at that time point minus the preprandial glucose value. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

  11. Change From Baseline of the 7-9-7 Point SMPG Profile: Fluctuation in 7-9-7 Point Profile [Week 0, week 16]

    Fluctuation in 7-point SMPG profile was the average absolute difference from the mean of the SMPG profile. Reported results are fluctuation in the 7-9-7 point SMPG profile from baseline (week 0) after 16 weeks of randomisation (i.e., week 16). The results are presented as ratio to baseline. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

  12. Change From Baseline of the 7-9-7 Point SMPG Profile: Nocturnal SMPG Measurements [Week 0, week 16]

    Change from baseline (week 0) in nocturnal SMPG measurements was assessed by considering the differences between PG values available at bedtime, at 4 AM and the before breakfast value the following day: (4 AM PG value minus at bedtime PG value), (before breakfast PG value minus at bedtime PG value) and (before breakfast PG value minus 4 AM PG value). Change from baseline in nocturnal increments in SMPG measurements of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation and presented during three different time intervals as follows: 1) 04:00 to breakfast, 2) bedtime to 04:00, and 3) bedtime to breakfast. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

  13. Participants Who Achieved Overall PPG (1 Hour) <7.8 mmol/L (140 mg/dL) (Yes/No) [16 weeks after randomisation]

    Participants reaching overall PPG (1 hour) ≤7.8 mmol/L [140 mg/dL] was evaluated after 16 weeks of randomisation. Participants without a postprandial glucose measurement at week 16 were considered not to have achieved HbA1c target at week 16. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

  14. Participants Who Achieved Overall PPG <7.8 mmol/L (140 mg/dL) Without Severe Hypoglycaemia Episodes (Yes/No) [16 weeks after randomisation]

    Participants reaching overall PPG (1 hour) ≤7.8 mmol/L [140 mg/dL] without severe hypoglycaemia episodes was evaluated after 16 weeks of randomisation. Participants without a postprandial glucose measurement at week 16 were considered not to have achieved HbA1c target at week 16. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

  15. Total Bolus Insulin Dose: in Units/Day [16 weeks from randomisation]

    Total bolus insulin dose (Units/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  16. Total Bolus Insulin Dose: in Units/kg/Day [16 weeks from randomisation]

    Total bolus insulin dose (Units/kg/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  17. Total Basal Insulin Dose: in Units/Day [16 weeks from randomisation]

    Total basal insulin dose (Units/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  18. Total Basal Insulin Dose: in Units/kg/Day [16 weeks from randomisation]

    Total basal insulin dose (Units/kg/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  19. Individual Meal Insulin Dose: in Units [16 weeks from randomisation]

    Individual meal time bolus insulin dose (Units) for breakast, lunch and main evening meal was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  20. Individual Meal Insulin Dose: in Units/kg [16 weeks from randomisation]

    Individual meal time bolus insulin dose (Units/kg) for breakast, lunch and main evening meal was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  21. Change From Baseline in Lipids-lipoproteins Profile (Total Cholesterol, High Density Lipoproteins, Low Density Lipoproteins) - Ratio to Baseline [Week 0, week 16]

    Reported results are lipids-lipoproteins (total cholesterol, high density lipoproteins, low density lipoproteins) values are given as ratio to baseline (week 0) after 16 weeks. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

  22. Number of Treatment Emergent Adverse Events [Weeks 0-16]

    Number of treatment emergent adverse events were recorded from week 0 to week 16. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  23. Number of Treatment Emergent Injection Site Reactions [Weeks 0-16]

    Number of treatment emergent injection site reactions were recorded from week 0 to week 16. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  24. Number of Treatment Emergent Hypoglycaemic Episodes (Hypos) According to the American Diabetes Association (ADA) and Novo Nordisk (NN) Definition: Overall [Weeks 0-16]

    ADA classification of hypos: Severe: Requiring assistance of another person to actively administer carbohydrate/glucagon/take other corrective actions. PG levels may not be available during an event, but neurological recovery following return of PG to normal is considered sufficient evidence that event was induced by a low PG level. Documented symptomatic: PG ≤3.9 mmol/L with symptoms. Asymptomatic: PG ≤3.9 mmol/L without symptoms. Probable symptomatic: No measurement with symptoms. Pseudo: PG >3.9 mmol/L with symptoms. Unclassifiable. NN classification of hypos: BG confirmed: PG <3.1 mmol/L with/without symptoms. Severe or BG confirmed symptomatic: Severe as per ADA and BG confirmed by PG <3.1 mmol/L with symptoms. Severe or BG confirmed: Severe as per ADA and BG confirmed by PG <3.1 mmol/L with/without symptoms. Unclassifiable. Not able to self treat-unclassifiable: Not able to self treat but not classifiable as severe hypoglycaemia.

  25. Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Daytime Hypoglycaemic Episodes (06:00-00:00 - Inclusive) [Weeks 0-16]

    Number of treatment emergent day time hypoglycaemic episodes according to the ADA and NN definitions were evaluated between 06:00 and 00:00 (both included). The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  26. Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Nocturnal Hypoglycaemic Episodes (00:01-05:59 - Inclusive) [Weeks 0-16]

    Number of treatment emergent nocturnal hypoglycaemic episodes according to the ADA and NN definitions were evaluated between 00:01 and 05:59 (both included). The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  27. Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 1 Hour After Start of the Meal [Weeks 0-16]

    Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated during the first 1 hour after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  28. Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 2 Hours After Start of the Meal [Weeks 0-16]

    Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated during the first 2 hours after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  29. Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 4 Hours After Start of the Meal [Weeks 0-16]

    Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated during the first 4 hours after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  30. Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and NN Definition: Hypoglycaemic Episodes Occurring Between 2 to 4 Hours After Start of the Meal [Weeks 0-16]

    Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated between 2 to 4 hours after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  31. Change From Baseline in Physical Examination [Week 0, week 16]

    Participants with physical examination findings, normal, abnormal NCS (non- clinically significant) and abnormal CS (clinically significant) at baseline (week 0) and week 16 presented. Results are based on the data from the on-treatment 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. Results are presented for the following examinations: 1) Cardiovascular system 2) Central & Peripheral nervous system 3) Gastrointestinal system incl. mouth 4) Head, ears, eyes, nose, throat and neck 5) Musculoskeletal system 6) Respiratory system 7) Skin

  32. Change From Baseline in Vital Signs: Systolic and Diastolic Blood Presure [Week 0, week 16]

    Change in vital signs - systolic and diastolic blood pressure from baseline (week 0) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  33. Change From Baseline in Vital Signs: Pulse [Week 0, week 16]

    Change in vital signs - pulse from baseline (week 0) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  34. Change From Baseline in Electrocardiogram (ECG) [Week 0, week 16]

    Changes in electrocardiogram (ECG) from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  35. Change From Baseline in Fundoscopy/Fundus Photography [Week 0, week 16]

    Changes in fundoscopy/fundus photography from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  36. Change From Baseline in Haematology - Haematocrit [Week 0, week 16]

    Changes in haematology - haematocrit from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  37. Change From Baseline in Haematology - Haemoglobin [Week 0, week 16]

    Changes in haematology - haemoglobin from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  38. Change From Baseline in Haematology - Leukocytes [Week 0, week 16]

    Changes in haematology - leukocytes from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  39. Change From Baseline in Haematology - Thrombocytes [Week 0, week 16]

    Changes in haematology - thrombocytes from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  40. Change From Baseline in Haematology - Erythrocytes [Week 0, week 16]

    Changes in haematology - erythrocytes from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  41. Change From Baseline in Biochemistry - Alanine Aminotransferase (ALT) [Week 0, week 16]

    Changes in biochemistry - alanine aminotransferase from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  42. Change From Baseline in Biochemistry - Alkaline Phosphatase [Week 0, week 16]

    Changes in biochemistry - alkaline phosphatase from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  43. Change From Baseline in Biochemistry - Aspartate Aminotransferase (AST) [Week 0, week 16]

    Changes in biochemistry - aspratate aminotransferase from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  44. Change From Baseline in Biochemistry - Albumin [Week 0, week 16]

    Changes in biochemistry - albumin from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  45. Change From Baseline in Biochemistry - Creatinine [Week 0, week 16]

    Changes in biochemistry - creatinine from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  46. Change From Baseline in Biochemistry - Potassium [Week 0, week 16]

    Changes in biochemistry - potassium from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  47. Change From Baseline in Biochemistry - Sodium [Week 0, week 16]

    Changes in biochemistry - sodium from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  48. Change From Baseline in Biochemistry - Total Bilirubin [Week 0, week 16]

    Changes in biochemistry - total bilirubin from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  49. Change From Baseline in Biochemistry - Total Protein [Week 0, week 16]

    Changes in biochemistry - total protein from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  50. Change From Baseline in Body Weight [Week 0, week 16]

    Changes in body weight from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

  51. Change From Baseline in Body Mass Index (BMI) [Week 0, week 16]

    Change in the body mass index (BMI) from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Eligibility Criteria

Criteria

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

Inclusion Criteria: - Male or female, age equal to or above 18 years at the time of signing informed consent. - Diagnosed with type 2 diabetes mellitus for 10 years or longer prior to screening (Visit 1). - Treated with a basal-bolus insulin regimen for 1 year or longer prior to the day of screening (Visit 1). A basal-bolus insulin regimen is defined as basal insulin once or twice daily and bolus insulin analogue taken with meals at least 3 times daily. Treatment with premixed insulin or soluble insulin combination is not considered a basal-bolus regimen. - Treated with or without oral antidiabetic drugs including extended release formulations. - HbA1c 7.0-10.0% (both inclusive) as assessed by central laboratory at screening (Visit 1). Exclusion Criteria: - Any of the following: myocardial infarction, stroke, hospitalization for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening (Visit 1). - Subjects presently classified as being in New York Heart Association (NYHA) Class IV. - Planned coronary, carotid or peripheral artery revascularisation known on the day of screening (Visit 1). - Treatment with injectable GLP-1 receptor agonists in a period of 90 days prior to screening (Visit 1). - Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or corticosteroids).

Contacts and Locations

Locations

Site City State Country Postal Code
1 Novo Nordisk Investigational Site Concord California United States 94520
2 Novo Nordisk Investigational Site Fresno California United States 93720
3 Novo Nordisk Investigational Site Fullerton California United States 92835
4 Novo Nordisk Investigational Site Lancaster California United States 93534
5 Novo Nordisk Investigational Site Norco California United States 92860
6 Novo Nordisk Investigational Site Sacramento California United States 95821
7 Novo Nordisk Investigational Site Ventura California United States 93003
8 Novo Nordisk Investigational Site Walnut Creek California United States 94598
9 Novo Nordisk Investigational Site Denver Colorado United States 80246
10 Novo Nordisk Investigational Site Golden Colorado United States 80401
11 Novo Nordisk Investigational Site Waterbury Connecticut United States 06708
12 Novo Nordisk Investigational Site Boynton Beach Florida United States 33472
13 Novo Nordisk Investigational Site Bradenton Florida United States 34201
14 Novo Nordisk Investigational Site Fort Lauderdale Florida United States 33312
15 Novo Nordisk Investigational Site Miami Florida United States 33174
16 Novo Nordisk Investigational Site Tampa Florida United States 33634
17 Novo Nordisk Investigational Site Alpharetta Georgia United States 30022
18 Novo Nordisk Investigational Site Lawrenceville Georgia United States 30046
19 Novo Nordisk Investigational Site Roswell Georgia United States 30076
20 Novo Nordisk Investigational Site Honolulu Hawaii United States 96814
21 Novo Nordisk Investigational Site Chicago Illinois United States 60611
22 Novo Nordisk Investigational Site Peoria Illinois United States 61603
23 Novo Nordisk Investigational Site Springfield Illinois United States 62711
24 Novo Nordisk Investigational Site Valparaiso Indiana United States 46383
25 Novo Nordisk Investigational Site West Des Moines Iowa United States 50266
26 Novo Nordisk Investigational Site Topeka Kansas United States 66606
27 Novo Nordisk Investigational Site Lexington Kentucky United States 40502
28 Novo Nordisk Investigational Site Lexington Kentucky United States 40503
29 Novo Nordisk Investigational Site Rockville Maryland United States 20852
30 Novo Nordisk Investigational Site Waltham Massachusetts United States 02453
31 Novo Nordisk Investigational Site Worcester Massachusetts United States 01655
32 Novo Nordisk Investigational Site Henderson Nevada United States 89052-2649
33 Novo Nordisk Investigational Site Las Vegas Nevada United States 89148
34 Novo Nordisk Investigational Site Nashua New Hampshire United States 03063
35 Novo Nordisk Investigational Site Northport New York United States 11768
36 Novo Nordisk Investigational Site West Seneca New York United States 14224
37 Novo Nordisk Investigational Site Asheville North Carolina United States 28803
38 Novo Nordisk Investigational Site Chapel Hill North Carolina United States 27514
39 Novo Nordisk Investigational Site Mentor Ohio United States 44060
40 Novo Nordisk Investigational Site Oklahoma City Oklahoma United States 73104-5020
41 Novo Nordisk Investigational Site Philadelphia Pennsylvania United States 19140
42 Novo Nordisk Investigational Site Greenville South Carolina United States 29605-4254
43 Novo Nordisk Investigational Site Chattanooga Tennessee United States 37404
44 Novo Nordisk Investigational Site Chattanooga Tennessee United States 37411
45 Novo Nordisk Investigational Site Nashville Tennessee United States 37212
46 Novo Nordisk Investigational Site Amarillo Texas United States 79106
47 Novo Nordisk Investigational Site Austin Texas United States 78731
48 Novo Nordisk Investigational Site Austin Texas United States 78749
49 Novo Nordisk Investigational Site Beaumont Texas United States 77701
50 Novo Nordisk Investigational Site Dallas Texas United States 75226
51 Novo Nordisk Investigational Site Dallas Texas United States 75230
52 Novo Nordisk Investigational Site Dallas Texas United States 75231
53 Novo Nordisk Investigational Site Longview Texas United States 75605
54 Novo Nordisk Investigational Site Pearland Texas United States 77584
55 Novo Nordisk Investigational Site Round Rock Texas United States 78681
56 Novo Nordisk Investigational Site Ogden Utah United States 84405
57 Novo Nordisk Investigational Site Bennington Vermont United States 05201
58 Novo Nordisk Investigational Site South Burlington Vermont United States 05403
59 Novo Nordisk Investigational Site Chesapeake Virginia United States 23321
60 Novo Nordisk Investigational Site Winchester Virginia United States 22601-3834
61 Novo Nordisk Investigational Site Olympia Washington United States 98502
62 Novo Nordisk Investigational Site Seattle Washington United States 98105
63 Novo Nordisk Investigational Site Spokane Washington United States 99201
64 Novo Nordisk Investigational Site Green Bay Wisconsin United States 54303
65 Novo Nordisk Investigational Site Caba Argentina C1060ABA
66 Novo Nordisk Investigational Site Caba Argentina C1440AAD
67 Novo Nordisk Investigational Site Cordoba Argentina 5000
68 Novo Nordisk Investigational Site Córdoba Argentina 5008
69 Novo Nordisk Investigational Site Kozloduy Bulgaria 3320
70 Novo Nordisk Investigational Site Razgrad Bulgaria 7200
71 Novo Nordisk Investigational Site Sofia Bulgaria 1233
72 Novo Nordisk Investigational Site Sofia Bulgaria 1618
73 Novo Nordisk Investigational Site Edmonton Alberta Canada T6G 2E1
74 Novo Nordisk Investigational Site Victoria British Columbia Canada V8V 4A1
75 Novo Nordisk Investigational Site Halifax Nova Scotia Canada B3H 2Y9
76 Novo Nordisk Investigational Site Barrie Ontario Canada L4N 7L3
77 Novo Nordisk Investigational Site Concord Ontario Canada L4K 4M2
78 Novo Nordisk Investigational Site Etobicoke Ontario Canada M9R 4E1
79 Novo Nordisk Investigational Site Hamilton Ontario Canada L8M 1K7
80 Novo Nordisk Investigational Site Newmarket Ontario Canada L3Y 5G8
81 Novo Nordisk Investigational Site Thunder Bay Ontario Canada P7A 4V7
82 Novo Nordisk Investigational Site Toronto Ontario Canada M4G 3E8
83 Novo Nordisk Investigational Site Montreal Quebec Canada H4T 1Z9
84 Novo Nordisk Investigational Site Karlovac Croatia 47000
85 Novo Nordisk Investigational Site Osijek Croatia 31 000
86 Novo Nordisk Investigational Site Varazdin Croatia 42 000
87 Novo Nordisk Investigational Site Zagreb Croatia 10 000
88 Novo Nordisk Investigational Site Hradec Kralove Czechia 500 05
89 Novo Nordisk Investigational Site Plzen Czechia 30100
90 Novo Nordisk Investigational Site Plzen Czechia 32600
91 Novo Nordisk Investigational Site Trutnov Czechia 541 01
92 Novo Nordisk Investigational Site Dresden Germany 01219
93 Novo Nordisk Investigational Site Essen Germany 45136
94 Novo Nordisk Investigational Site Falkensee Germany 14612
95 Novo Nordisk Investigational Site Lingen Germany 49808
96 Novo Nordisk Investigational Site Münster Germany 48145
97 Novo Nordisk Investigational Site Saint Ingbert-Oberwürzbach Germany 66386
98 Novo Nordisk Investigational Site Schweinfurt Germany 97421
99 Novo Nordisk Investigational Site Athens Greece 115 25
100 Novo Nordisk Investigational Site Athens Greece GR-11527
101 Novo Nordisk Investigational Site Ioannina Greece 45500
102 Novo Nordisk Investigational Site Larissa Greece GR-41110
103 Novo Nordisk Investigational Site Thessaloniki Greece GR-54636
104 Novo Nordisk Investigational Site Thessaloniki Greece GR-54642
105 Novo Nordisk Investigational Site Thessaloniki Greece GR-54643
106 Novo Nordisk Investigational Site Thessaloniki Greece GR-57001
107 Novo Nordisk Investigational Site Catanzaro Italy 88100
108 Novo Nordisk Investigational Site Chieti Italy 66100
109 Novo Nordisk Investigational Site Cittadella (PD) Italy 35013
110 Novo Nordisk Investigational Site Milano (MI) Italy 20132
111 Novo Nordisk Investigational Site Olbia Italy 07026
112 Novo Nordisk Investigational Site Palermo Italy 90129
113 Novo Nordisk Investigational Site Bucheon Korea, Republic of 14647
114 Novo Nordisk Investigational Site Daegu Korea, Republic of 42472
115 Novo Nordisk Investigational Site Seongnam-si Korea, Republic of 463-707
116 Novo Nordisk Investigational Site Seoul Korea, Republic of 02447
117 Novo Nordisk Investigational Site Seoul Korea, Republic of 03080
118 Novo Nordisk Investigational Site Seoul Korea, Republic of 04516
119 Novo Nordisk Investigational Site Seoul Korea, Republic of 06351
120 Novo Nordisk Investigational Site Seoul Korea, Republic of 08308
121 Novo Nordisk Investigational Site Seoul Korea, Republic of 137-701
122 Novo Nordisk Investigational Site Wonju Korea, Republic of 26426
123 Novo Nordisk Investigational Site Bialystok Poland 15-435
124 Novo Nordisk Investigational Site Skorzewo Poland 60-185
125 Novo Nordisk Investigational Site Warsaw Poland 00-465
126 Novo Nordisk Investigational Site Warsaw Poland 02-793
127 Novo Nordisk Investigational Site Warszawa Poland 02-507
128 Novo Nordisk Investigational Site Wroclaw Poland 50-381
129 Novo Nordisk Investigational Site Ponce Puerto Rico 00716
130 Novo Nordisk Investigational Site Baia Mare Maramures Romania 430222
131 Novo Nordisk Investigational Site Tirgu Mures Mures Romania 540142
132 Novo Nordisk Investigational Site Timisoara Timis Romania 300125
133 Novo Nordisk Investigational Site Brasov Romania 500101
134 Novo Nordisk Investigational Site Brasov Romania 500283
135 Novo Nordisk Investigational Site Bucharest Romania 13682
136 Novo Nordisk Investigational Site Arkhangelsk Russian Federation 163045
137 Novo Nordisk Investigational Site Kazan Russian Federation 420073
138 Novo Nordisk Investigational Site Moscow Russian Federation 123448
139 Novo Nordisk Investigational Site Penza Russian Federation 440026
140 Novo Nordisk Investigational Site Saint Petersburg Russian Federation 194291
141 Novo Nordisk Investigational Site Saint-Petersburg Russian Federation 194356
142 Novo Nordisk Investigational Site Tumen Russian Federation 625023
143 Novo Nordisk Investigational Site Voronezh Russian Federation 394018
144 Novo Nordisk Investigational Site Belgrade Serbia 11000
145 Novo Nordisk Investigational Site Kragujevac Serbia 34000
146 Novo Nordisk Investigational Site Nis Serbia 18000
147 Novo Nordisk Investigational Site Novi Sad Serbia 21000
148 Novo Nordisk Investigational Site Zajecar Serbia 19000
149 Novo Nordisk Investigational Site Kosice Slovakia 040 01
150 Novo Nordisk Investigational Site Kysucke Nove Mesto Slovakia 024 01
151 Novo Nordisk Investigational Site Lubochna Slovakia 03491
152 Novo Nordisk Investigational Site Lucenec Slovakia 984 01
153 Novo Nordisk Investigational Site Zilina Slovakia 01001
154 Novo Nordisk Investigational Site Alcobendas Spain 28100
155 Novo Nordisk Investigational Site Almería Spain 04001
156 Novo Nordisk Investigational Site Girona Spain 17007
157 Novo Nordisk Investigational Site La Coruña Spain 15006
158 Novo Nordisk Investigational Site Pozuelo de Alarcon Spain 28223
159 Novo Nordisk Investigational Site Sabadell Spain 08208
160 Novo Nordisk Investigational Site Sevilla Spain 41003
161 Novo Nordisk Investigational Site Sevilla Spain 41010
162 Novo Nordisk Investigational Site Dnipro Ukraine 49038
163 Novo Nordisk Investigational Site Kharkiv Ukraine 61000
164 Novo Nordisk Investigational Site Kyiv Ukraine 03049
165 Novo Nordisk Investigational Site Lviv Ukraine 79010
166 Novo Nordisk Investigational Site Ternopil Ukraine 46002
167 Novo Nordisk Investigational Site Vinnytsia Ukraine 21010

Sponsors and Collaborators

  • Novo Nordisk A/S

Investigators

None specified.

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT03268005
Other Study ID Numbers:
  • NN1218-4113
  • U1111-1180-0636
  • 2016-000878-38
First Posted:
Aug 31, 2017
Last Update Posted:
Jan 11, 2022
Last Verified:
Jan 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 trial was conducted at 165 sites in 17 countries as follows: Argentina-3, Bulgaria-4, Canada-10, Croatia-4, Czech Republic-4, Germany-6, Greece-8, Italy-4, Poland-10, Republic of Korea-6, Romania-6, Russia-8, Serbia-9, Slovakia-5, Spain-8, Ukraine-6 and United States (US)-62. Two sites in the US screened but didn't randomise any subject.
Pre-assignment Detail There was a 12-week run-in period primarily for optimisation of the basal insulin and reinforcement of subject training in trial procedures, diabetes education and dietary training. Out of the 1264 participants enrolled in the study, 173 were run-in failures and 1091 were randomised.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Period Title: Overall Study
STARTED 546 545
Full Analysis Set 546 545
Safety Analysis Set 544 544
COMPLETED 531 531
NOT COMPLETED 15 14

Baseline Characteristics

Arm/Group Title Faster Aspart NovoRapid Total
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Total of all reporting groups
Overall Participants 546 545 1091
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
62.6
(8.6)
62.1
(8.8)
62.3
(8.7)
Sex: Female, Male (Count of Participants)
Female
281
51.5%
256
47%
537
49.2%
Male
265
48.5%
289
53%
554
50.8%
Race/Ethnicity, Customized (Count of Participants)
White
487
89.2%
487
89.4%
974
89.3%
Asian
43
7.9%
31
5.7%
74
6.8%
Black or African American
14
2.6%
19
3.5%
33
3%
Native Hawaiian or Other Pacific Islander
2
0.4%
5
0.9%
7
0.6%
Other
0
0%
3
0.6%
3
0.3%
Race/Ethnicity, Customized (Count of Participants)
Not Hispanic or Latino
485
88.8%
488
89.5%
973
89.2%
Hispanic Latino
61
11.2%
57
10.5%
118
10.8%

Outcome Measures

1. Primary Outcome
Title Change in Glycosylated Haemoglobin (HbA1c)
Description Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 16. The endpoint was evaluated based on data from the in-trial observation period. In-trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 544 539
Mean (Standard Deviation) [Percentage of HbA1c]
-0.15
(0.62)
-0.09
(0.60)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Faster Aspart, NovoRapid
Comments Change from baseline in HbA1c was analysed using an analysis of variance model after multiple imputation assuming treatment according to randomisation. The model included treatment, region and metformin use at baseline (Yes/No) as factors, and baseline HbA1c as a covariate.
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 95% confidence interval for the difference between faster aspart and NovoRapid was compared to a non-inferiority margin of 0.4%. If it was below or equal to 0.4% non-inferiority was considered established and effect demonstrated.
Statistical Test of Hypothesis p-Value 0.310
Comments
Method ANOVA
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.11 to 0.03
Parameter Dispersion Type:
Value:
Estimation Comments Faster aspart-NovoRapid
2. Secondary Outcome
Title Change From Baseline in 1-hour PPG Increment
Description Change from baseline (week 0) in 1-hour postprandial glucose (PPG) increment was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 519 523
Mean (Standard Deviation) [mmol/L]
-0.43
(2.45)
0.08
(2.65)
3. Secondary Outcome
Title Change From Baseline in 1,5-anhydroglucitol
Description Change from baseline (week 0) in 1,5-anhydroglucitol was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 534 531
Mean (Standard Deviation) [mmol/L]
1.38
(3.10)
0.89
(3.31)
4. Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (FPG)
Description Change from baseline (week 0) in fasting plasma glucose was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 533 530
Mean (Standard Deviation) [mmol/L]
0.56
(2.38)
0.68
(2.40)
5. Secondary Outcome
Title Participants Who Achieved HbA1c <7.0% (53 mmol/L) (Yes/No)
Description Number of participants reaching HbA1c <7.0% (53 mmol/L) was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time Frame 16 weeks after randomisation

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 Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 546 545
Yes
271
49.6%
282
51.7%
No
275
50.4%
263
48.3%
6. Secondary Outcome
Title Participants Who Achieved HbA1c <7.0% (53 mmol/L) Without Severe Hypoglycaemia Episodes (Yes/No)
Description Number of participants reaching HbA1c <7.0% (53 mmol/L) without severe hypoglycaemia episodes was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time Frame 16 weeks after randomisation

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 Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 546 545
Yes
265
48.5%
278
51%
No
281
51.5%
267
49%
7. Secondary Outcome
Title Change From Baseline (Week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour Postprandial Glucose (PPG [Meal Test])
Description Change from baseline (week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour postprandial glucose (PPG [meal test]) was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact. Meal test: The subjects were given a carbohydrate-rich standardised liquid meal immediately after bolus (faster aspart or NovoRapid) infusion in the morning of the meal test. The subjects were to consume the meal as quickly as possible (within 12 minutes) and blood samples were drawn after 30 minutes, 1, 2, 3 and 4 hours from the start of the meal.
Time Frame Week 0, week 16

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 Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 546 545
30-min
0.31
(2.90)
0.55
(2.80)
1-hour
0.03
(3.30)
0.68
(3.23)
2-hour
0.08
(3.96)
0.61
(3.48)
3-hour
0.30
(3.85)
0.89
(3.72)
4-hour
0.51
(3.47)
0.75
(3.51)
8. Secondary Outcome
Title Change From Baseline (Week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour PPG Increment (Meal Test)
Description Change from baseline (week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour PPG increment (meal test) was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact. Meal test: The subjects were given a carbohydrate-rich standardised liquid meal immediately after bolus (faster aspart or NovoRapid) infusion in the morning of the meal test. The subjects were to consume the meal as quickly as possible (within 12 minutes) and blood samples were drawn after 30 minutes, 1, 2, 3 and 4 hours from the start of the meal. PPG incremental value for each time point was derived as PPG value at that time point minus the preprandial glucose value.
Time Frame Week 0, week 16

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 Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 546 545
30-min
-0.13
(1.85)
-0.05
(1.95)
1-hour
-0.43
(2.45)
0.08
(2.65)
2-hour
-0.37
(3.25)
0.001
(3.13)
3-hour
-0.15
(3.23)
0.28
(3.54)
4-hour
0.04
(3.00)
0.15
(3.45)
9. Secondary Outcome
Title Change From Baseline in Mean of the 7-9-7 Point Self-measured Plasma Glucose (SMPG) Profile
Description Change from baseline (week 0) in mean of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. 7-9-7 point SMPG was measured at the following mentioned time points: 1) Before breakfast, 2) 60 mins after the start of Breakfast, 3) Before lunch, 4) 60 mins after the start of lunch, 5) Before main evening meal, 6) 60 mins after the start of main evening meal, 7) At bedtime, 8) At 4 AM, 9) Before breakfast.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 454 464
Mean (Standard Deviation) [mmol/L]
-0.56
(1.66)
-0.50
(1.61)
10. Secondary Outcome
Title Change From Baseline of the 7-9-7 Point SMPG Profile: PPG (Mean, Breakfast, Lunch and Main Evening Meal)
Description Change from baseline (week 0) in PPG (breakfast, lunch, main evening meal and mean over all meals) of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time Frame Week 0, week 16

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 Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 546 545
Breakfast
-0.38
(2.53)
-0.28
(2.44)
Lunch
-0.78
(2.48)
-0.58
(2.68)
Main evening meal
-1.04
(2.67)
-0.71
(2.50)
All meals
-0.75
(1.89)
-0.52
(1.91)
11. Secondary Outcome
Title Change From Baseline of the 7-9-7 Point SMPG Profile: PPG Increment (Mean, Breakfast, Lunch and Main Evening Meal)
Description Change from baseline (week 0) in PPG increment (breakfast, lunch, main evening meal and mean over all meals) of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. PPG increment based on the 7-9-7-point profiles were derived separately for PG measurements made at 1 hour after main meals (breakfast, lunch and main evening meal). PPG incremental value for each time point was derived as PPG value at that time point minus the preprandial glucose value. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time Frame Week 0, week 16

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 Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 546 545
Breakfast
-0.56
(2.23)
-0.42
(2.17)
Lunch
-0.38
(2.69)
-0.23
(2.46)
Main evening meal
-0.44
(2.61)
-0.10
(2.28)
All meals
-0.48
(1.55)
-0.23
(1.42)
12. Secondary Outcome
Title Change From Baseline of the 7-9-7 Point SMPG Profile: Fluctuation in 7-9-7 Point Profile
Description Fluctuation in 7-point SMPG profile was the average absolute difference from the mean of the SMPG profile. Reported results are fluctuation in the 7-9-7 point SMPG profile from baseline (week 0) after 16 weeks of randomisation (i.e., week 16). The results are presented as ratio to baseline. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 454 464
Geometric Mean (Geometric Coefficient of Variation) [Ratio]
0.82
(48.32)
0.85
(55.06)
13. Secondary Outcome
Title Change From Baseline of the 7-9-7 Point SMPG Profile: Nocturnal SMPG Measurements
Description Change from baseline (week 0) in nocturnal SMPG measurements was assessed by considering the differences between PG values available at bedtime, at 4 AM and the before breakfast value the following day: (4 AM PG value minus at bedtime PG value), (before breakfast PG value minus at bedtime PG value) and (before breakfast PG value minus 4 AM PG value). Change from baseline in nocturnal increments in SMPG measurements of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation and presented during three different time intervals as follows: 1) 04:00 to breakfast, 2) bedtime to 04:00, and 3) bedtime to breakfast. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time Frame Week 0, week 16

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 Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 546 545
Bedtime to 04:00
0.70
(4.09)
0.29
(4.09)
Bedtime to breakfast
1.30
(4.25)
0.90
(3.99)
04:00 to breakfast
0.66
(2.76)
0.75
(2.87)
14. Secondary Outcome
Title Participants Who Achieved Overall PPG (1 Hour) <7.8 mmol/L (140 mg/dL) (Yes/No)
Description Participants reaching overall PPG (1 hour) ≤7.8 mmol/L [140 mg/dL] was evaluated after 16 weeks of randomisation. Participants without a postprandial glucose measurement at week 16 were considered not to have achieved HbA1c target at week 16. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time Frame 16 weeks after randomisation

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 Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 546 545
Yes
186
34.1%
192
35.2%
No
360
65.9%
353
64.8%
15. Secondary Outcome
Title Participants Who Achieved Overall PPG <7.8 mmol/L (140 mg/dL) Without Severe Hypoglycaemia Episodes (Yes/No)
Description Participants reaching overall PPG (1 hour) ≤7.8 mmol/L [140 mg/dL] without severe hypoglycaemia episodes was evaluated after 16 weeks of randomisation. Participants without a postprandial glucose measurement at week 16 were considered not to have achieved HbA1c target at week 16. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time Frame 16 weeks after randomisation

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 Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 546 545
Yes
182
33.3%
190
34.9%
No
364
66.7%
355
65.1%
16. Secondary Outcome
Title Total Bolus Insulin Dose: in Units/Day
Description Total bolus insulin dose (Units/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame 16 weeks from randomisation

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 544 542
Mean (Standard Deviation) [Units/day]
54.72
(35.82)
53.38
(35.35)
17. Secondary Outcome
Title Total Bolus Insulin Dose: in Units/kg/Day
Description Total bolus insulin dose (Units/kg/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame 16 weeks from randomisation

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 544 542
Mean (Standard Deviation) [Units/kg/day]
0.57
(0.33)
0.55
(0.34)
18. Secondary Outcome
Title Total Basal Insulin Dose: in Units/Day
Description Total basal insulin dose (Units/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame 16 weeks from randomisation

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 544 542
Mean (Standard Deviation) [Units/day]
63.76
(35.21)
62.25
(36.03)
19. Secondary Outcome
Title Total Basal Insulin Dose: in Units/kg/Day
Description Total basal insulin dose (Units/kg/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame 16 weeks from randomisation

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 544 542
Mean (Standard Deviation) [Units/kg/day]
0.66
(0.32)
0.64
(0.32)
20. Secondary Outcome
Title Individual Meal Insulin Dose: in Units
Description Individual meal time bolus insulin dose (Units) for breakast, lunch and main evening meal was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame 16 weeks from randomisation

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 544 544
Breakfast
16.27
(12.04)
15.52
(11.38)
Lunch
18.51
(12.09)
17.96
(11.73)
Daily main evening meal
19.88
(13.46)
19.85
(14.47)
21. Secondary Outcome
Title Individual Meal Insulin Dose: in Units/kg
Description Individual meal time bolus insulin dose (Units/kg) for breakast, lunch and main evening meal was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame 16 weeks from randomisation

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 544 544
Breakfast
0.17
(0.12)
0.16
(0.11)
Lunch
0.19
(0.11)
0.19
(0.12)
Daily main evening meal
0.21
(0.13)
0.20
(0.14)
22. Secondary Outcome
Title Change From Baseline in Lipids-lipoproteins Profile (Total Cholesterol, High Density Lipoproteins, Low Density Lipoproteins) - Ratio to Baseline
Description Reported results are lipids-lipoproteins (total cholesterol, high density lipoproteins, low density lipoproteins) values are given as ratio to baseline (week 0) after 16 weeks. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time Frame Week 0, week 16

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 Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 546 545
Total cholesterol
1.01
(15.98)
1.00
(17.09)
High density lipoproteins
0.97
(14.47)
0.98
(17.57)
Low density lipoproteins
0.99
(25.36)
0.99
(40.51)
23. Secondary Outcome
Title Number of Treatment Emergent Adverse Events
Description Number of treatment emergent adverse events were recorded from week 0 to week 16. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Weeks 0-16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 544 544
Number [Events]
667
643
24. Secondary Outcome
Title Number of Treatment Emergent Injection Site Reactions
Description Number of treatment emergent injection site reactions were recorded from week 0 to week 16. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Weeks 0-16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 544 544
Number [Number of injection site reactions]
3
1
25. Secondary Outcome
Title Number of Treatment Emergent Hypoglycaemic Episodes (Hypos) According to the American Diabetes Association (ADA) and Novo Nordisk (NN) Definition: Overall
Description ADA classification of hypos: Severe: Requiring assistance of another person to actively administer carbohydrate/glucagon/take other corrective actions. PG levels may not be available during an event, but neurological recovery following return of PG to normal is considered sufficient evidence that event was induced by a low PG level. Documented symptomatic: PG ≤3.9 mmol/L with symptoms. Asymptomatic: PG ≤3.9 mmol/L without symptoms. Probable symptomatic: No measurement with symptoms. Pseudo: PG >3.9 mmol/L with symptoms. Unclassifiable. NN classification of hypos: BG confirmed: PG <3.1 mmol/L with/without symptoms. Severe or BG confirmed symptomatic: Severe as per ADA and BG confirmed by PG <3.1 mmol/L with symptoms. Severe or BG confirmed: Severe as per ADA and BG confirmed by PG <3.1 mmol/L with/without symptoms. Unclassifiable. Not able to self treat-unclassifiable: Not able to self treat but not classifiable as severe hypoglycaemia.
Time Frame Weeks 0-16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 544 544
ADA: Severe
18
14
ADA: Documented symptomatic
5038
6165
ADA: Asymptomatic
3761
3681
ADA: Probable symptomatic
68
68
ADA: Pseudo
145
75
ADA: Unclassifiable
3
3
NN: BG confirmed
2209
2735
NN: Severe or BG confirmed symptomatic
1490
2055
NN: Severe or BG confirmed
2227
2749
NN: Unclassifiable
6806
7257
Not able to selftreat - unclassifiable
0
0
26. Secondary Outcome
Title Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Daytime Hypoglycaemic Episodes (06:00-00:00 - Inclusive)
Description Number of treatment emergent day time hypoglycaemic episodes according to the ADA and NN definitions were evaluated between 06:00 and 00:00 (both included). The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Weeks 0-16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 544 544
ADA: Severe
16
12
ADA: Documented symptomatic
4703
5700
ADA: Asymptomatic
3617
3484
ADA: Probable symptomatic
62
64
ADA: Pseudo
141
66
ADA: Unclassifiable
3
3
NN: BG confirmed
2016
2442
NN: Severe or BG confirmed symptomatic
1333
1814
NN: Severe or BG confirmed
2032
2454
NN: Unclassifiable
6510
6875
Not able to selftreat - unclassifiable
0
0
27. Secondary Outcome
Title Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Nocturnal Hypoglycaemic Episodes (00:01-05:59 - Inclusive)
Description Number of treatment emergent nocturnal hypoglycaemic episodes according to the ADA and NN definitions were evaluated between 00:01 and 05:59 (both included). The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Weeks 0-16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 544 544
ADA: Severe
2
2
ADA: Documented symptomatic
335
465
ADA: Asymptomatic
144
197
ADA: Probable symptomatic
6
4
ADA: Pseudo
4
9
ADA: Unclassifiable
0
0
NN: BG confirmed
193
293
NN: Severe or BG confirmed symptomatic
157
241
NN: Severe or BG confirmed
195
295
NN: Unclassifiable
296
382
Not able to selftreat - unclassifiable
0
0
28. Secondary Outcome
Title Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 1 Hour After Start of the Meal
Description Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated during the first 1 hour after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Weeks 0-16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 544 544
ADA: Severe
2
0
ADA: Documented symptomatic
149
148
ADA: Asymptomatic
87
80
ADA: Probable symptomatic
11
8
ADA: Pseudo
2
4
ADA: Unclassifiable
0
0
NN: BG confirmed
72
65
NN: Severe or BG confirmed symptomatic
48
50
NN: Severe or BG confirmed
74
65
NN: Unclassifiable
177
175
Not able to selftreat - unclassifiable
0
0
29. Secondary Outcome
Title Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 2 Hours After Start of the Meal
Description Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated during the first 2 hours after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Weeks 0-16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 544 544
ADA: Severe
2
1
ADA: Documented symptomatic
465
446
ADA: Asymptomatic
201
159
ADA: Probable symptomatic
16
11
ADA: Pseudo
10
7
ADA: Unclassifiable
0
0
NN: BG confirmed
233
246
NN: Severe or BG confirmed symptomatic
181
212
NN: Severe or BG confirmed
235
247
NN: Unclassifiable
459
377
Not able to selftreat - unclassifiable
0
0
30. Secondary Outcome
Title Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 4 Hours After Start of the Meal
Description Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated during the first 4 hours after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Weeks 0-16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 544 544
ADA: Severe
6
9
ADA: Documented symptomatic
1627
1882
ADA: Asymptomatic
852
744
ADA: Probable symptomatic
37
27
ADA: Pseudo
55
26
ADA: Unclassifiable
0
0
NN: BG confirmed
762
965
NN: Severe or BG confirmed symptomatic
557
820
NN: Severe or BG confirmed
768
974
NN: Unclassifiable
1809
1714
Not able to selftreat - unclassifiable
0
0
31. Secondary Outcome
Title Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and NN Definition: Hypoglycaemic Episodes Occurring Between 2 to 4 Hours After Start of the Meal
Description Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated between 2 to 4 hours after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Weeks 0-16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 544 544
ADA: Severe
4
8
ADA: Documented symptomatic
1162
1436
ADA: Asymptomatic
651
585
ADA: Probable symptomatic
21
16
ADA: Pseudo
45
19
ADA: Unclassifiable
0
0
NN: BG confirmed
529
719
NN: Severe or BG confirmed symptomatic
376
608
NN: Severe or BG confirmed
533
727
NN: Unclassifiable
1350
1337
Not able to selftreat - unclassifiable
0
0
32. Secondary Outcome
Title Change From Baseline in Physical Examination
Description Participants with physical examination findings, normal, abnormal NCS (non- clinically significant) and abnormal CS (clinically significant) at baseline (week 0) and week 16 presented. Results are based on the data from the on-treatment 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. Results are presented for the following examinations: 1) Cardiovascular system 2) Central & Peripheral nervous system 3) Gastrointestinal system incl. mouth 4) Head, ears, eyes, nose, throat and neck 5) Musculoskeletal system 6) Respiratory system 7) Skin
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 544 544
Normal
459
84.1%
460
84.4%
Abnormal NCS
79
14.5%
79
14.5%
Abnormal CS
6
1.1%
5
0.9%
Normal
448
82.1%
457
83.9%
Abnormal NCS
71
13%
72
13.2%
Abnormal CS
6
1.1%
4
0.7%
Normal
398
72.9%
404
74.1%
Abnormal NCS
133
24.4%
127
23.3%
Abnormal CS
13
2.4%
13
2.4%
Normal
383
70.1%
400
73.4%
Abnormal NCS
128
23.4%
122
22.4%
Abnormal CS
14
2.6%
11
2%
Normal
491
89.9%
485
89%
Abnormal NCS
53
9.7%
59
10.8%
Abnormal CS
0
0%
0
0%
Normal
480
87.9%
476
87.3%
Abnormal NCS
45
8.2%
57
10.5%
Abnormal CS
0
0%
0
0%
Normal
498
91.2%
492
90.3%
Abnormal NCS
43
7.9%
48
8.8%
Abnormal CS
3
0.5%
4
0.7%
Normal
485
88.8%
483
88.6%
Abnormal NCS
40
7.3%
49
9%
Abnormal CS
0
0%
1
0.2%
Normal
504
92.3%
496
91%
Abnormal NCS
36
6.6%
42
7.7%
Abnormal CS
4
0.7%
6
1.1%
Normal
489
89.6%
494
90.6%
Abnormal NCS
32
5.9%
33
6.1%
Abnormal CS
4
0.7%
6
1.1%
Normal
535
98%
534
98%
Abnormal NCS
9
1.6%
9
1.7%
Abnormal CS
0
0%
1
0.2%
Normal
520
95.2%
517
94.9%
Abnormal NCS
5
0.9%
14
2.6%
Abnormal CS
0
0%
2
0.4%
Normal
438
80.2%
429
78.7%
Abnormal NCS
96
17.6%
108
19.8%
Abnormal CS
10
1.8%
7
1.3%
Normal
418
76.6%
430
78.9%
Abnormal NCS
98
17.9%
98
18%
Abnormal CS
9
1.6%
5
0.9%
33. Secondary Outcome
Title Change From Baseline in Vital Signs: Systolic and Diastolic Blood Presure
Description Change in vital signs - systolic and diastolic blood pressure from baseline (week 0) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 525 533
Systolic blood pressure
0.4
(14.0)
-1.2
(14.8)
Diastolic blood pressure
-0.4
(8.9)
-0.7
(8.9)
34. Secondary Outcome
Title Change From Baseline in Vital Signs: Pulse
Description Change in vital signs - pulse from baseline (week 0) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 525 533
Mean (Standard Deviation) [Beats per min]
0.5
(9.0)
0.03
(8.9)
35. Secondary Outcome
Title Change From Baseline in Electrocardiogram (ECG)
Description Changes in electrocardiogram (ECG) from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 544 544
Normal
287
52.6%
270
49.5%
Abnormal NCS
252
46.2%
264
48.4%
Abnormal CS
5
0.9%
10
1.8%
Normal
274
50.2%
272
49.9%
Abnormal NCS
245
44.9%
253
46.4%
Abnormal CS
6
1.1%
8
1.5%
36. Secondary Outcome
Title Change From Baseline in Fundoscopy/Fundus Photography
Description Changes in fundoscopy/fundus photography from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 544 544
Normal
225
41.2%
219
40.2%
Abnormal NCS
287
52.6%
297
54.5%
Abnormal CS
32
5.9%
27
5%
Normal
205
37.5%
198
36.3%
Abnormal NCS
278
50.9%
288
52.8%
Abnormal CS
31
5.7%
30
5.5%
Normal
224
41%
217
39.8%
Abnormal NCS
288
52.7%
300
55%
Abnormal CS
32
5.9%
27
5%
Normal
208
38.1%
194
35.6%
Abnormal NCS
276
50.5%
297
54.5%
Abnormal CS
30
5.5%
26
4.8%
37. Secondary Outcome
Title Change From Baseline in Haematology - Haematocrit
Description Changes in haematology - haematocrit from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 532 536
Mean (Standard Deviation) [Percentage]
0.48
(2.47)
0.35
(2.47)
38. Secondary Outcome
Title Change From Baseline in Haematology - Haemoglobin
Description Changes in haematology - haemoglobin from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 532 536
Mean (Standard Deviation) [mmol/L]
-0.02
(0.47)
-0.04
(0.43)
39. Secondary Outcome
Title Change From Baseline in Haematology - Leukocytes
Description Changes in haematology - leukocytes from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 532 536
Mean (Standard Deviation) [10^9 leukocytes/L]
0.01
(1.60)
-0.01
(1.35)
40. Secondary Outcome
Title Change From Baseline in Haematology - Thrombocytes
Description Changes in haematology - thrombocytes from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 531 533
Mean (Standard Deviation) [10^9 thrombocytes/L]
-0.9
(37.1)
-1.3
(38.7)
41. Secondary Outcome
Title Change From Baseline in Haematology - Erythrocytes
Description Changes in haematology - erythrocytes from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 532 536
Mean (Standard Deviation) [10^12 erythrocytes/L]
-0.02
(0.28)
-0.04
(0.27)
42. Secondary Outcome
Title Change From Baseline in Biochemistry - Alanine Aminotransferase (ALT)
Description Changes in biochemistry - alanine aminotransferase from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 532 536
Mean (Standard Deviation) [U/L]
-0.1
(9.4)
3.1
(65.4)
43. Secondary Outcome
Title Change From Baseline in Biochemistry - Alkaline Phosphatase
Description Changes in biochemistry - alkaline phosphatase from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 532 536
Mean (Standard Deviation) [U/L]
2.9
(22.6)
2.2
(18.3)
44. Secondary Outcome
Title Change From Baseline in Biochemistry - Aspartate Aminotransferase (AST)
Description Changes in biochemistry - aspratate aminotransferase from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 532 536
Mean (Standard Deviation) [U/L]
-0.2
(7.9)
2.2
(45.7)
45. Secondary Outcome
Title Change From Baseline in Biochemistry - Albumin
Description Changes in biochemistry - albumin from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 532 536
Mean (Standard Deviation) [g/dL]
0.02
(0.25)
0.01
(0.26)
46. Secondary Outcome
Title Change From Baseline in Biochemistry - Creatinine
Description Changes in biochemistry - creatinine from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 532 536
Mean (Standard Deviation) [umol/L]
0.1
(11.1)
1.5
(13.2)
47. Secondary Outcome
Title Change From Baseline in Biochemistry - Potassium
Description Changes in biochemistry - potassium from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 532 536
Mean (Standard Deviation) [mmol/L]
-0.001
(0.50)
0.02
(0.43)
48. Secondary Outcome
Title Change From Baseline in Biochemistry - Sodium
Description Changes in biochemistry - sodium from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 532 536
Mean (Standard Deviation) [mmol/L]
-0.6
(2.6)
-0.7
(2.8)
49. Secondary Outcome
Title Change From Baseline in Biochemistry - Total Bilirubin
Description Changes in biochemistry - total bilirubin from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 531 536
Mean (Standard Deviation) [umol/L]
0.1
(2.7)
0.1
(3.0)
50. Secondary Outcome
Title Change From Baseline in Biochemistry - Total Protein
Description Changes in biochemistry - total protein from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 532 536
Mean (Standard Deviation) [g/dL]
-0.01
(0.35)
-0.02
(0.36)
51. Secondary Outcome
Title Change From Baseline in Body Weight
Description Changes in body weight from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 522 530
Mean (Standard Deviation) [kg]
1.19
(2.95)
1.12
(4.01)
52. Secondary Outcome
Title Change From Baseline in Body Mass Index (BMI)
Description Change in the body mass index (BMI) from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time Frame Week 0, week 16

Outcome Measure Data

Analysis Population Description
Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Measure Participants 522 530
Mean (Standard Deviation) [kg/m^2]
0.43
(1.04)
0.40
(1.40)

Adverse Events

Time Frame Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE).
Adverse Event Reporting Description All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Arm/Group Title Faster Aspart NovoRapid
Arm/Group Description Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion. Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
All Cause Mortality
Faster Aspart NovoRapid
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 2/544 (0.4%) 1/544 (0.2%)
Serious Adverse Events
Faster Aspart NovoRapid
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 38/544 (7%) 40/544 (7.4%)
Blood and lymphatic system disorders
Haemorrhagic anaemia 0/544 (0%) 0 1/544 (0.2%) 1
Iron deficiency anaemia 1/544 (0.2%) 1 0/544 (0%) 0
Cardiac disorders
Acute coronary syndrome 2/544 (0.4%) 2 0/544 (0%) 0
Acute myocardial infarction 1/544 (0.2%) 1 0/544 (0%) 0
Angina pectoris 0/544 (0%) 0 2/544 (0.4%) 2
Angina unstable 1/544 (0.2%) 1 1/544 (0.2%) 1
Arteriosclerosis coronary artery 1/544 (0.2%) 1 1/544 (0.2%) 1
Atrial fibrillation 1/544 (0.2%) 1 1/544 (0.2%) 1
Bradycardia 1/544 (0.2%) 1 1/544 (0.2%) 1
Cardiac failure 2/544 (0.4%) 2 1/544 (0.2%) 1
Cardiac failure congestive 0/544 (0%) 0 2/544 (0.4%) 2
Coronary artery disease 0/544 (0%) 0 2/544 (0.4%) 2
Left ventricular failure 1/544 (0.2%) 1 0/544 (0%) 0
Mitral valve incompetence 0/544 (0%) 0 1/544 (0.2%) 1
Myocardial ischaemia 1/544 (0.2%) 1 0/544 (0%) 0
Eye disorders
Vitreous haemorrhage 1/544 (0.2%) 1 0/544 (0%) 0
Gastrointestinal disorders
Colitis 0/544 (0%) 0 1/544 (0.2%) 1
Cyclic vomiting syndrome 1/544 (0.2%) 1 0/544 (0%) 0
Diarrhoea 1/544 (0.2%) 1 0/544 (0%) 0
Duodenal ulcer 1/544 (0.2%) 1 0/544 (0%) 0
Gastritis erosive 1/544 (0.2%) 1 0/544 (0%) 0
Obstructive pancreatitis 0/544 (0%) 0 1/544 (0.2%) 1
Small intestinal obstruction 1/544 (0.2%) 1 0/544 (0%) 0
General disorders
Chest pain 0/544 (0%) 0 1/544 (0.2%) 1
Pain 1/544 (0.2%) 1 0/544 (0%) 0
Hepatobiliary disorders
Bile duct obstruction 1/544 (0.2%) 1 0/544 (0%) 0
Infections and infestations
Bronchitis 1/544 (0.2%) 1 0/544 (0%) 0
Device related sepsis 0/544 (0%) 0 1/544 (0.2%) 1
Gangrene 0/544 (0%) 0 2/544 (0.4%) 2
Gastroenteritis viral 0/544 (0%) 0 1/544 (0.2%) 1
Infective exacerbation of chronic obstructive airways disease 0/544 (0%) 0 1/544 (0.2%) 2
Lower respiratory tract infection 1/544 (0.2%) 1 0/544 (0%) 0
Orchitis 1/544 (0.2%) 1 0/544 (0%) 0
Osteomyelitis 0/544 (0%) 0 1/544 (0.2%) 1
Pneumonia 2/544 (0.4%) 2 1/544 (0.2%) 1
Respiratory tract infection 0/544 (0%) 0 2/544 (0.4%) 2
Upper respiratory tract infection 1/544 (0.2%) 1 0/544 (0%) 0
Injury, poisoning and procedural complications
Accidental overdose 2/544 (0.4%) 2 0/544 (0%) 0
Contusion 0/544 (0%) 0 1/544 (0.2%) 1
Fall 0/544 (0%) 0 1/544 (0.2%) 1
Fibula fracture 1/544 (0.2%) 1 1/544 (0.2%) 1
Humerus fracture 1/544 (0.2%) 1 0/544 (0%) 0
Road traffic accident 0/544 (0%) 0 1/544 (0.2%) 1
Wrong product administered 1/544 (0.2%) 1 1/544 (0.2%) 1
Investigations
Cardiac stress test abnormal 1/544 (0.2%) 1 0/544 (0%) 0
Metabolism and nutrition disorders
Dehydration 1/544 (0.2%) 1 0/544 (0%) 0
Hyperglycaemia 0/544 (0%) 0 1/544 (0.2%) 1
Hypoglycaemia 4/544 (0.7%) 4 3/544 (0.6%) 3
Musculoskeletal and connective tissue disorders
Arthritis 1/544 (0.2%) 1 0/544 (0%) 0
Lumbar spinal stenosis 0/544 (0%) 0 1/544 (0.2%) 1
Spinal pain 1/544 (0.2%) 1 0/544 (0%) 0
Trigger finger 0/544 (0%) 0 1/544 (0.2%) 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon 1/544 (0.2%) 1 0/544 (0%) 0
Hepatocellular carcinoma 1/544 (0.2%) 1 0/544 (0%) 0
Invasive ductal breast carcinoma 0/544 (0%) 0 1/544 (0.2%) 1
Lung neoplasm malignant 0/544 (0%) 0 1/544 (0.2%) 1
Pancreatic carcinoma metastatic 1/544 (0.2%) 1 0/544 (0%) 0
Nervous system disorders
Cerebellar infarction 1/544 (0.2%) 1 0/544 (0%) 0
Diabetic neuropathy 0/544 (0%) 0 1/544 (0.2%) 1
Dizziness 0/544 (0%) 0 2/544 (0.4%) 2
Encephalopathy 1/544 (0.2%) 1 0/544 (0%) 0
Haemorrhagic stroke 0/544 (0%) 0 1/544 (0.2%) 1
Headache 0/544 (0%) 0 1/544 (0.2%) 1
Hypoglycaemic unconsciousness 3/544 (0.6%) 3 0/544 (0%) 0
Transient ischaemic attack 2/544 (0.4%) 2 1/544 (0.2%) 1
Vascular parkinsonism 1/544 (0.2%) 1 0/544 (0%) 0
Product Issues
Device malfunction 0/544 (0%) 0 1/544 (0.2%) 1
Psychiatric disorders
Delusion 1/544 (0.2%) 1 0/544 (0%) 0
Rapid eye movements sleep abnormal 1/544 (0.2%) 1 0/544 (0%) 0
Renal and urinary disorders
Acute kidney injury 0/544 (0%) 0 1/544 (0.2%) 1
Renal failure 0/544 (0%) 0 1/544 (0.2%) 1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease 0/544 (0%) 0 2/544 (0.4%) 2
Pulmonary oedema 1/544 (0.2%) 1 0/544 (0%) 0
Respiratory failure 0/544 (0%) 0 1/544 (0.2%) 1
Surgical and medical procedures
Aortic valve replacement 1/544 (0.2%) 1 0/544 (0%) 0
Carpal tunnel decompression 0/544 (0%) 0 1/544 (0.2%) 1
Rehabilitation therapy 0/544 (0%) 0 1/544 (0.2%) 1
Vitrectomy 1/544 (0.2%) 1 0/544 (0%) 0
Vascular disorders
Aortic aneurysm 0/544 (0%) 0 1/544 (0.2%) 1
Deep vein thrombosis 0/544 (0%) 0 1/544 (0.2%) 1
Hypotension 0/544 (0%) 0 1/544 (0.2%) 1
Peripheral vascular disorder 1/544 (0.2%) 1 0/544 (0%) 0
Subclavian vein occlusion 0/544 (0%) 0 1/544 (0.2%) 1
Varicose ulceration 0/544 (0%) 0 1/544 (0.2%) 1
Other (Not Including Serious) Adverse Events
Faster Aspart NovoRapid
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 32/544 (5.9%) 33/544 (6.1%)
Infections and infestations
Nasopharyngitis 32/544 (5.9%) 35 33/544 (6.1%) 36

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:
NCT03268005
Other Study ID Numbers:
  • NN1218-4113
  • U1111-1180-0636
  • 2016-000878-38
First Posted:
Aug 31, 2017
Last Update Posted:
Jan 11, 2022
Last Verified:
Jan 1, 2022