A Study to Assess the Addition of Sitagliptin to Metformin Compared With the Addition of Dapagliflozin to Metformin in Participants With Type 2 Diabetes Mellitus (T2DM) and Mild Renal Impairment Who Have Inadequate Glycemic Control on Metformin With or Without a Sulfonylurea (MK-0431-838)
Study Details
Study Description
Brief Summary
The purpose of the study is to assess the effect of the addition of sitagliptin to metformin with or without a sulfonylurea compared with the addition of dapagliflozin to metformin with or without a sulfonylurea on hemoglobin A1c (A1C) over 24 weeks of treatment as well as the overall safety and tolerability of sitagliptin in comparison to that of dapagliflozin after 24 weeks of treatment. The primary hypothesis is that the change from baseline in A1C in participants treated with the addition of sitagliptin is non-inferior compared to that in participants treated with the addition of dapagliflozin after 24 weeks of treatment.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Sitagliptin Participants receive sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 5 mg once daily for 4 weeks followed by sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 10 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. |
Drug: Sitagliptin
Sitagliptin 100 mg oral tablet
Drug: Metformin
This medication is a standard-of-care medication and is administered in an open-label fashion. Supply of background metformin oral tablet(s) (at least 1500 mg daily) will be the responsibility of the participant throughout the duration of the study.
Drug: Matching placebo to dapagliflozin
Matching placebo to dapagliflozin 5 mg or 10 mg oral capsule. Up-titration to matching placebo to dapagliflozin 10 mg daily may be delayed if participant is unable to tolerate up-titration in the opinion of the investigator. Matching placebo to dapagliflozin 10 mg daily may be down-titrated to matching placebo to dapagliflozin 5 mg daily if participant is unable to tolerate the higher dose in the opinion of the investigator.
Drug: Sulfonylurea
This medication is a standard-of-care medication and is administered in an open-label fashion. The dose of the sulfonylurea agent will be required to be at least 50% of maximum labeled dose, consistent with near maximum efficacy of the sulfonylurea agent.
|
| Active Comparator: Dapagliflozin Participants receive dapagliflozin 5 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 4 weeks followed by dapagliflozin 10 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. |
Drug: Dapagliflozin
Dapagliflozin 5 mg or 10 mg oral capsule. Up-titration to dapagliflozin 10 mg daily may be delayed if participant is unable to tolerate up-titration in the opinion of the investigator. Dapagliflozin 10 mg daily may be down-titrated to dapagliflozin 5 mg daily if participant is unable to tolerate the higher dose in the opinion of the investigator.
Drug: Metformin
This medication is a standard-of-care medication and is administered in an open-label fashion. Supply of background metformin oral tablet(s) (at least 1500 mg daily) will be the responsibility of the participant throughout the duration of the study.
Drug: Matching placebo to sitagliptin
Matching placebo to sitagliptin 100 mg oral tablet
Drug: Sulfonylurea
This medication is a standard-of-care medication and is administered in an open-label fashion. The dose of the sulfonylurea agent will be required to be at least 50% of maximum labeled dose, consistent with near maximum efficacy of the sulfonylurea agent.
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in A1C at Week 24 [Baseline and Week 24]
A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 24 A1C minus the Week 0 A1C.
- Percentage of Participants Who Experienced One or More Adverse Events [Up to 26 weeks]
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product. The AE does not have to have a causal relationship with this treatment. The AE can include any unfavourable and unintended sign, symptom, or disease or any worsening (change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the pharmaceutical product.
- Percentage of Participants Who Discontinued Study Drug Due to an AE [Up to 24 weeks]
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product. The AE does not have to have a causal relationship with this treatment. The AE can include any unfavourable and unintended sign, symptom, or disease or any worsening (change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the pharmaceutical product.
Secondary Outcome Measures
- Change From Baseline in Incremental 2-hour (2-hr) Postprandial Glucose Excursion (PPGE) at Week 24 [Immediately before and 120 minutes after the standard meal at Baseline and Week 24]
The 2hr PPGE is the change from baseline in the mean incremental change in post meal glucose defined as T-120 minus T-0 for each participant: change from baseline PPGE = Week 24 mean (T-120 minus T-0) minus Baseline mean (T-120 minus T-0). The 2-point MMTT measured values at T-0 and T-120 while the 3-point MMTT measured values at T-0, T-60, and T-120: although only a subset of the study had the 3-point MMTT performed, all participants had a T-0 and T-120 time point. A negative (-) change from baseline to Week 24 indicates better control of postprandial glucose.
- Change From Baseline in 2-hr Postprandial Glucose (PPG) at Week 24 [Immediately before and 120 minutes after the standard meal at Baseline and Week 24]
The 2hr PPG is the change from baseline in mean post prandial glucose (change from baseline PPG = Week 24 mean T-120 glucose minus Baseline mean T-120 glucose) and shows each drugs impact on PPG. The 2-point MMTT measured values at T-0 and T-120 while the 3-point MMTT measured values at T-0, T-60, and T-120: although only a subset of the study had the 3-point MMTT performed, all participants had a T-0 and T-120 time point. A negative (-) change from baseline to Week 24 indicates better control of postprandial glucose.
- Change From Baseline in Glucagon Area Under the Curve (AUC0-120 Minutes) at Week 24 [Immediately before and 60 and 120 minutes after the standard meal at Baseline and Week 24]
AUC endpoints were analyzed for participants who underwent the 3-point MMTT. Blood samples were drawn immediately prior to (T=0 minutes) and 60 and 120 minutes after the administration of the standard meal. The AUC curve was generated with the 3 time points. If any time point for a given participant was missing, the AUC was not included. Change in Postprandial Glucagon AUC after the morning meal (t=0 to 120 minutes) was calculated from the glucagon AUC over the first 120 minutes following the morning meal at baseline minus glucagon AUC over the first 120 minutes following the morning meal at Week 24. A negative (-) change from baseline to Week 24 indicates better control of postprandial glucose.
- Change From Baseline in Insulin AUC0-120 Minutes at Week 24 [Immediately before and 60 and 120 minutes after the standard meal at Baseline and Week 24]
AUC endpoints were analyzed for participants who underwent the 3-point MMTT. Blood samples were drawn immediately prior to (T=0 minutes) and 60 and 120 minutes after the administration of the standard meal. The AUC curve was generated with the 3 time points. If any time point for a given participant was missing, the AUC was not included. Change in Postprandial Insulin AUC after the morning meal (t=0 to 120 minutes) was calculated from insulin AUC over the first 120 minutes following the morning meal at baseline minus insulin AUC over the first 120 minutes following the morning meal at Week 24. A negative (-) change from baseline to Week 24 indicates better control of postprandial glucose.
- Change From Baseline in Postprandial Insulin AUC0-120 Minutes to Glucagon AUC0-120 Minutes Ratio at Week 24 [Immediately before and 60 and 120 minutes after the standard meal at Baseline and Week 24]
AUC endpoints were analyzed for participants who underwent the 3-point MMTT. Blood samples were drawn immediately prior to (T=0 minutes) and 60 and 120 minutes after the administration of the standard meal. The AUC curve was generated with the 3 time points. If any time point for a given participant was missing, the AUC was not included. The endpoint was calculated from the ratio of (insulin AUC / glucagon AUC) over the first 120 minutes following the morning meal at baseline minus AUC over the first 120 minutes following the morning meal at Week 24. A negative (-) change from baseline to Week 24 indicates better control of postprandial glucose.
- Percentage of Participants With A1C <7% (53 mmol/Mol) at Week 24 [Week 24]
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100.
- Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 [Baseline and Week 24]
Blood glucose was measured on a fasting basis. Blood was drawn at predose on Day 1 and after 24 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 24 minus FPG at Week 0).
Eligibility Criteria
Criteria
Inclusion Criteria
-
Have T2DM at Screening visit
-
Be on metformin monotherapy ≥1500 mg/day alone or in combination with an sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) for ≥8 weeks
-
Is a male or a female not of reproductive potential (defined as one who is postmenopausal or has had a hysterectomy and/or bilateral oophorectomy, or had bilateral tubal ligation or occlusion at least 6 weeks prior to Screening visit). If participant is a female of reproductive potential, must agree to remain abstinent from heterosexual activity or agrees to use (or have her partner use) acceptable contraception to prevent pregnancy while receiving blinded study drug and for 14 days after the last dose of blinded study drug
Exclusion Criteria:
-
Has a history of type 1 diabetes mellitus or a history of ketoacidosis
-
Has a history of secondary causes of diabetes
-
Has a known hypersensitivity or intolerance to any dipeptidyl peptidase IV (DPP-4) inhibitor or sodium-glucose cotransporter 2 (SGLT2) inhibitor
-
Has been treated with any anti-hyperglycemic agents (AHA) other than metformin and for participants on dual combination therapy, a sulfonylurea within 12 weeks of screening
-
Intends to initiate weight loss medication during the study period
-
Has undergone bariatric surgery within 12 months of Screening visit
-
Has started a weight loss medication or a medication associated with weight changes within the prior 12 weeks.
-
Has a history of myocardial infarction, unstable angina, arterial revascularization, stroke, transient ischemic attack, heart failure within 3 months of Screening visit
-
Has a history of malignancy ≤5 years prior to study, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
-
Has human immunodeficiency virus (HIV)
-
Has blood dyscrasias or any disorders causing hemolysis or unstable red blood cells, or clinically important hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
-
Has a medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease
-
Is currently being treated for hyperthyroidism or is on thyroid replacement therapy and has not been on a stable dose for at least 6 weeks prior to Screening visit
-
Is on or likely to require treatment for ≥14 consecutive days or repeated courses of corticosteroids
-
Is on or likely to require treatment for ≥7 consecutive days with non-steroidal anti-inflammatory drugs
-
Is pregnant or breast-feeding, or is planning to conceive during the study, including 14 days following the last dose of blinded study drug
-
Is planning to undergo hormonal therapy in preparation to donate eggs during the study, including 14 days following the last dose of blinded study drug
-
Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week or engages in binge drinking
-
Has donated blood or blood products within 6 weeks of Screening visit or who plans to donate blood or blood products at any time during the study
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
More Information
Publications
None provided.- 0431-838
- 2014-005525-13
- MK-0431-838
Study Results
Participant Flow
| Recruitment Details | This study was conducted at 183 medical centers in 24 countries. |
|---|---|
| Pre-assignment Detail | Male and female participants, 25 years or older, with Type 2 diabetes mellitus (T2DM) and mild renal impairment on metformin alone or in combination with a sulfonylurea (SU) agent were enrolled in this trial. |
| Arm/Group Title | Sitagliptin | Dapagliflozin |
|---|---|---|
| Arm/Group Description | Participants receive sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 5 mg once daily for 4 weeks followed by sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 10 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. | Participants receive dapagliflozin 5 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 4 weeks followed by dapagliflozin 10 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. |
| Period Title: Overall Study | ||
| STARTED | 307 | 307 |
| Treated | 307 | 306 |
| COMPLETED | 299 | 296 |
| NOT COMPLETED | 8 | 11 |
Baseline Characteristics
| Arm/Group Title | Sitagliptin | Dapagliflozin | Total |
|---|---|---|---|
| Arm/Group Description | Participants receive sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 5 mg once daily for 4 weeks followed by sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 10 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. | Participants receive dapagliflozin 5 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 4 weeks followed by dapagliflozin 10 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. | Total of all reporting groups |
| Overall Participants | 307 | 306 | 613 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
67.7
(8.5)
|
66.6
(8.6)
|
67.1
(8.5)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
138
45%
|
120
39.2%
|
258
42.1%
|
| Male |
169
55%
|
186
60.8%
|
355
57.9%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
18
5.9%
|
14
4.6%
|
32
5.2%
|
| Asian |
11
3.6%
|
7
2.3%
|
18
2.9%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
1
0.3%
|
1
0.2%
|
| Black or African American |
8
2.6%
|
11
3.6%
|
19
3.1%
|
| White |
240
78.2%
|
234
76.5%
|
474
77.3%
|
| More than one race |
30
9.8%
|
39
12.7%
|
69
11.3%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Hemoglobin A1C (Percent A1C) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Percent A1C] |
7.7
(0.7)
|
7.8
(0.7)
|
7.7
(0.7)
|
| Fasting Plasma Glucose (FPG) (mg/dL) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mg/dL] |
162.3
(40.4)
|
165.2
(40.6)
|
163.8
(40.5)
|
| Background Antihyperglycemic Agent (AHA) (Count of Participants) | |||
| Metformin Alone |
212
69.1%
|
225
73.5%
|
437
71.3%
|
| Metformin and Sulfonylurea |
95
30.9%
|
81
26.5%
|
176
28.7%
|
| Incremental 2-hour Postprandial Glucose Excursion (PPGE) (mg/dL) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mg/dL] |
96.2
(55.3)
|
95.7
(47.1)
|
95.9
(51.4)
|
| 2-hr Postprandial Glucose (mg/dL) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mg/dL] |
257.7
(67.1)
|
259.9
(64.4)
|
258.8
(65.7)
|
| Glucagon Area Under the Curve (AUC0-120 minutes) (pmol.hr/L) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [pmol.hr/L] |
49.6
(44.7)
|
51.8
(45.1)
|
50.7
(44.8)
|
| Insulin AUC0-120 minutes (mIU.hr/L) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mIU.hr/L] |
155.0
(121.8)
|
139.9
(93.5)
|
147.5
(108.7)
|
| Insulin AUC0-120 minutes to Glucagon AUC0-120 minutes Ratio (Ratio) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Ratio] |
4.0
(3.7)
|
3.5
(3.0)
|
3.8
(3.4)
|
Outcome Measures
| Title | Change From Baseline in A1C at Week 24 |
|---|---|
| Description | A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 24 A1C minus the Week 0 A1C. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized and treated participants who had at least one observation for the analysis endpoint, at baseline or subsequent to at least one dose of study treatment. |
| Arm/Group Title | Sitagliptin | Dapagliflozin |
|---|---|---|
| Arm/Group Description | Participants receive sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 5 mg once daily for 4 weeks followed by sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 10 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. | Participants receive dapagliflozin 5 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 4 weeks followed by dapagliflozin 10 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. |
| Measure Participants | 307 | 306 |
| Least Squares Mean (95% Confidence Interval) [Percent A1C] |
-0.51
|
-0.36
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sitagliptin, Dapagliflozin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority | |
| Comments | For the primary hypothesis, sitagliptin will be considered non-inferior to dapagliflozin if the upper bound of the two-sided 95% confidence interval (CI) of the between-group difference in least squares mean change from baseline in A1C (sitagliptin minus dapagliflozin) is less than 0.3% (the non-inferiority margin). Longitudinal data analysis (LDA), Antihyperglycemic agent (AHA), Least squares means (LSM) | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LSM (Sit. - Dap.) |
| Estimated Value | -0.15 | |
| Confidence Interval |
(2-Sided) 95% -0.26 to -0.04 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Sitagliptin, Dapagliflozin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.006 |
| Comments | ||
| Method | Longitudinal data analysis | |
| Comments | LDA model including terms for treatment, time, background AHA, the interaction of time and background AHA, and the interaction of time by treatment. | |
| Method of Estimation | Estimation Parameter | Difference in LSM (Sit. - Dap.) |
| Estimated Value | -0.15 | |
| Confidence Interval |
(2-Sided) 95% -0.26 to -0.04 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Who Experienced One or More Adverse Events |
|---|---|
| Description | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product. The AE does not have to have a causal relationship with this treatment. The AE can include any unfavourable and unintended sign, symptom, or disease or any worsening (change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the pharmaceutical product. |
| Time Frame | Up to 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized and treated participants. |
| Arm/Group Title | Sitagliptin | Dapagliflozin |
|---|---|---|
| Arm/Group Description | Participants receive sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 5 mg once daily for 4 weeks followed by sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 10 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. | Participants receive dapagliflozin 5 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 4 weeks followed by dapagliflozin 10 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. |
| Measure Participants | 307 | 306 |
| Number [Percentage of participants] |
48.9
15.9%
|
51.6
16.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sitagliptin, Dapagliflozin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in % (Sit. - Dap.) |
| Estimated Value | -2.8 | |
| Confidence Interval |
(2-Sided) 95% -10.7 to 5.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Who Discontinued Study Drug Due to an AE |
|---|---|
| Description | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product. The AE does not have to have a causal relationship with this treatment. The AE can include any unfavourable and unintended sign, symptom, or disease or any worsening (change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the pharmaceutical product. |
| Time Frame | Up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized and treated participants. |
| Arm/Group Title | Sitagliptin | Dapagliflozin |
|---|---|---|
| Arm/Group Description | Participants receive sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 5 mg once daily for 4 weeks followed by sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 10 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. | Participants receive dapagliflozin 5 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 4 weeks followed by dapagliflozin 10 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. |
| Measure Participants | 307 | 306 |
| Number [Percentage of participants] |
3.3
1.1%
|
3.3
1.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sitagliptin, Dapagliflozin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in % (Sit. - Dap.) |
| Estimated Value | -0.0 | |
| Confidence Interval |
(2-Sided) 95% -3.0 to 3.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Incremental 2-hour (2-hr) Postprandial Glucose Excursion (PPGE) at Week 24 |
|---|---|
| Description | The 2hr PPGE is the change from baseline in the mean incremental change in post meal glucose defined as T-120 minus T-0 for each participant: change from baseline PPGE = Week 24 mean (T-120 minus T-0) minus Baseline mean (T-120 minus T-0). The 2-point MMTT measured values at T-0 and T-120 while the 3-point MMTT measured values at T-0, T-60, and T-120: although only a subset of the study had the 3-point MMTT performed, all participants had a T-0 and T-120 time point. A negative (-) change from baseline to Week 24 indicates better control of postprandial glucose. |
| Time Frame | Immediately before and 120 minutes after the standard meal at Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized and treated participants who underwent MMTT for the analysis endpoint, had both baseline and Week 24 endpoint measurements, without: drug compliance <75%, use of prohibited AHA medications or pharmacologic doses of corticosteroids or incorrect double-blind study drug or a change in metformin or sulfonylurea dose. |
| Arm/Group Title | Sitagliptin | Dapagliflozin |
|---|---|---|
| Arm/Group Description | Participants receive sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 5 mg once daily for 4 weeks followed by sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 10 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. | Participants receive dapagliflozin 5 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 4 weeks followed by dapagliflozin 10 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. |
| Measure Participants | 298 | 296 |
| Least Squares Mean (95% Confidence Interval) [mg/dL] |
-24.2
|
-18.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sitagliptin, Dapagliflozin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.138 |
| Comments | ||
| Method | LDA | |
| Comments | LDA model including terms for treatment, time, background AHA, the interaction of time and background AHA, and the interaction of time by treatment. | |
| Method of Estimation | Estimation Parameter | Difference in LSM (Sit. - Dap.) |
| Estimated Value | -5.7 | |
| Confidence Interval |
(2-Sided) 95% -13.3 to 1.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in 2-hr Postprandial Glucose (PPG) at Week 24 |
|---|---|
| Description | The 2hr PPG is the change from baseline in mean post prandial glucose (change from baseline PPG = Week 24 mean T-120 glucose minus Baseline mean T-120 glucose) and shows each drugs impact on PPG. The 2-point MMTT measured values at T-0 and T-120 while the 3-point MMTT measured values at T-0, T-60, and T-120: although only a subset of the study had the 3-point MMTT performed, all participants had a T-0 and T-120 time point. A negative (-) change from baseline to Week 24 indicates better control of postprandial glucose. |
| Time Frame | Immediately before and 120 minutes after the standard meal at Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized and treated participants who underwent MMTT for the analysis endpoint, had both baseline and Week 24 endpoint measurements, without: drug compliance <75%, use of prohibited AHA medications or pharmacologic doses of corticosteroids or incorrect double-blind study drug or a change in metformin or sulfonylurea dose. |
| Arm/Group Title | Sitagliptin | Dapagliflozin |
|---|---|---|
| Arm/Group Description | Participants receive sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 5 mg once daily for 4 weeks followed by sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 10 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. | Participants receive dapagliflozin 5 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 4 weeks followed by dapagliflozin 10 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. |
| Measure Participants | 258 | 248 |
| Least Squares Mean (95% Confidence Interval) [mg/dL] |
-40.4
|
-37.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sitagliptin, Dapagliflozin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in the LSM (Sit. - Dap.) |
| Estimated Value | -3.4 | |
| Confidence Interval |
(2-Sided) 95% -12.1 to 5.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Glucagon Area Under the Curve (AUC0-120 Minutes) at Week 24 |
|---|---|
| Description | AUC endpoints were analyzed for participants who underwent the 3-point MMTT. Blood samples were drawn immediately prior to (T=0 minutes) and 60 and 120 minutes after the administration of the standard meal. The AUC curve was generated with the 3 time points. If any time point for a given participant was missing, the AUC was not included. Change in Postprandial Glucagon AUC after the morning meal (t=0 to 120 minutes) was calculated from the glucagon AUC over the first 120 minutes following the morning meal at baseline minus glucagon AUC over the first 120 minutes following the morning meal at Week 24. A negative (-) change from baseline to Week 24 indicates better control of postprandial glucose. |
| Time Frame | Immediately before and 60 and 120 minutes after the standard meal at Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized and treated participants who underwent MMTT for the analysis endpoint, had both baseline and Week 24 endpoint measurements, without: drug compliance <75%, use of prohibited AHA medications or pharmacologic doses of corticosteroids or incorrect double-blind study drug or a change in metformin or sulfonylurea dose. |
| Arm/Group Title | Sitagliptin | Dapagliflozin |
|---|---|---|
| Arm/Group Description | Participants receive sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 5 mg once daily for 4 weeks followed by sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 10 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. | Participants receive dapagliflozin 5 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 4 weeks followed by dapagliflozin 10 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. |
| Measure Participants | 85 | 88 |
| Least Squares Mean (95% Confidence Interval) [pmol.hr/L] |
-4.2
|
0.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sitagliptin, Dapagliflozin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in the LSM (Sit. - Dap.) |
| Estimated Value | -4.4 | |
| Confidence Interval |
(2-Sided) 95% -10.1 to 1.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Insulin AUC0-120 Minutes at Week 24 |
|---|---|
| Description | AUC endpoints were analyzed for participants who underwent the 3-point MMTT. Blood samples were drawn immediately prior to (T=0 minutes) and 60 and 120 minutes after the administration of the standard meal. The AUC curve was generated with the 3 time points. If any time point for a given participant was missing, the AUC was not included. Change in Postprandial Insulin AUC after the morning meal (t=0 to 120 minutes) was calculated from insulin AUC over the first 120 minutes following the morning meal at baseline minus insulin AUC over the first 120 minutes following the morning meal at Week 24. A negative (-) change from baseline to Week 24 indicates better control of postprandial glucose. |
| Time Frame | Immediately before and 60 and 120 minutes after the standard meal at Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized and treated participants who underwent MMTT for the analysis endpoint, had both baseline and Week 24 endpoint measurements, without: drug compliance <75%, use of prohibited AHA medications or pharmacologic doses of corticosteroids or incorrect double-blind study drug or a change in metformin or sulfonylurea dose. |
| Arm/Group Title | Sitagliptin | Dapagliflozin |
|---|---|---|
| Arm/Group Description | Participants receive sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 5 mg once daily for 4 weeks followed by sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 10 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. | Participants receive dapagliflozin 5 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 4 weeks followed by dapagliflozin 10 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. |
| Measure Participants | 96 | 94 |
| Least Squares Mean (95% Confidence Interval) [mIU.hr/L] |
-23.4
|
-28.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sitagliptin, Dapagliflozin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in the LSM (Sit. - Dap.) |
| Estimated Value | 4.9 | |
| Confidence Interval |
(2-Sided) 95% -12.2 to 22.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Postprandial Insulin AUC0-120 Minutes to Glucagon AUC0-120 Minutes Ratio at Week 24 |
|---|---|
| Description | AUC endpoints were analyzed for participants who underwent the 3-point MMTT. Blood samples were drawn immediately prior to (T=0 minutes) and 60 and 120 minutes after the administration of the standard meal. The AUC curve was generated with the 3 time points. If any time point for a given participant was missing, the AUC was not included. The endpoint was calculated from the ratio of (insulin AUC / glucagon AUC) over the first 120 minutes following the morning meal at baseline minus AUC over the first 120 minutes following the morning meal at Week 24. A negative (-) change from baseline to Week 24 indicates better control of postprandial glucose. |
| Time Frame | Immediately before and 60 and 120 minutes after the standard meal at Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized and treated participants who underwent MMTT for the analysis endpoint, had both baseline and Week 24 endpoint measurements, without: drug compliance <75%, use of prohibited AHA medications or pharmacologic doses of corticosteroids or incorrect double-blind study drug or a change in metformin or sulfonylurea dose. |
| Arm/Group Title | Sitagliptin | Dapagliflozin |
|---|---|---|
| Arm/Group Description | Participants receive sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 5 mg once daily for 4 weeks followed by sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 10 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. | Participants receive dapagliflozin 5 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 4 weeks followed by dapagliflozin 10 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. |
| Measure Participants | 83 | 81 |
| Least Squares Mean (95% Confidence Interval) [Ratio] |
-0.6
|
-1.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sitagliptin, Dapagliflozin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in the LSM (Sit. - Dap.) |
| Estimated Value | 0.6 | |
| Confidence Interval |
(2-Sided) 95% -0.1 to 1.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With A1C <7% (53 mmol/Mol) at Week 24 |
|---|---|
| Description | A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized and treated participants who had at least one observation for the analysis endpoint, at baseline or subsequent to at least one dose of study treatment. |
| Arm/Group Title | Sitagliptin | Dapagliflozin |
|---|---|---|
| Arm/Group Description | Participants receive sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 5 mg once daily for 4 weeks followed by sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 10 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. | Participants receive dapagliflozin 5 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 4 weeks followed by dapagliflozin 10 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. |
| Measure Participants | 307 | 306 |
| Number [Percentage of Participants] |
42.6
13.9%
|
27.0
8.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sitagliptin, Dapagliflozin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | The percentage of participants was estimated using standard multiple imputation techniques from LDA model including terms for treatment, time, background AHA, the interaction of time and background AHA, and the interaction of time by treatment. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in % (Sit. - Dap.) |
| Estimated Value | 15.5 | |
| Confidence Interval |
(2-Sided) 95% 7.7 to 23.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 |
|---|---|
| Description | Blood glucose was measured on a fasting basis. Blood was drawn at predose on Day 1 and after 24 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 24 minus FPG at Week 0). |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized and treated participants who had at least one observation for the analysis endpoint, at baseline or subsequent to at least one dose of study treatment. |
| Arm/Group Title | Sitagliptin | Dapagliflozin |
|---|---|---|
| Arm/Group Description | Participants receive sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 5 mg once daily for 4 weeks followed by sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 10 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. | Participants receive dapagliflozin 5 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 4 weeks followed by dapagliflozin 10 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. |
| Measure Participants | 307 | 306 |
| Least Squares Mean (95% Confidence Interval) [mg/dL] |
-16.5
|
-20.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sitagliptin, Dapagliflozin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in the LSM (Sit. - Dap.) |
| Estimated Value | 3.5 | |
| Confidence Interval |
(2-Sided) 95% -1.2 to 8.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Up to 26 weeks | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not have to have a causal relationship. The AE can include any unfavourable and unintended sign, symptom, or disease or any worsening (change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the pharmaceutical product. The population analyzed included all randomized and treated participants. | |||
| Arm/Group Title | Sitagliptin | Dapagliflozin | ||
| Arm/Group Description | Participants receive sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 5 mg once daily for 4 weeks followed by sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 10 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. | Participants receive dapagliflozin 5 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 4 weeks followed by dapagliflozin 10 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. | ||
All Cause Mortality |
||||
| Sitagliptin | Dapagliflozin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/307 (0%) | 0/306 (0%) | ||
Serious Adverse Events |
||||
| Sitagliptin | Dapagliflozin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/307 (3.3%) | 13/306 (4.2%) | ||
| Cardiac disorders | ||||
| Acute myocardial infarction | 1/307 (0.3%) | 1 | 0/306 (0%) | 0 |
| Atrioventricular block second degree | 0/307 (0%) | 0 | 1/306 (0.3%) | 1 |
| Coronary artery disease | 1/307 (0.3%) | 1 | 0/306 (0%) | 0 |
| Coronary artery stenosis | 1/307 (0.3%) | 1 | 0/306 (0%) | 0 |
| Myocardial infarction | 0/307 (0%) | 0 | 1/306 (0.3%) | 1 |
| Sinus node dysfunction | 1/307 (0.3%) | 1 | 0/306 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Enterocolitis | 0/307 (0%) | 0 | 1/306 (0.3%) | 1 |
| Pancreatitis acute | 0/307 (0%) | 0 | 1/306 (0.3%) | 1 |
| Reflux gastritis | 1/307 (0.3%) | 1 | 0/306 (0%) | 0 |
| Upper gastrointestinal haemorrhage | 0/307 (0%) | 0 | 1/306 (0.3%) | 1 |
| General disorders | ||||
| Non-cardiac chest pain | 0/307 (0%) | 0 | 1/306 (0.3%) | 1 |
| Hepatobiliary disorders | ||||
| Cholangitis | 1/307 (0.3%) | 1 | 0/306 (0%) | 0 |
| Infections and infestations | ||||
| Atypical pneumonia | 1/307 (0.3%) | 1 | 0/306 (0%) | 0 |
| Influenza | 0/307 (0%) | 0 | 1/306 (0.3%) | 1 |
| Pneumonia | 0/307 (0%) | 0 | 1/306 (0.3%) | 1 |
| Sepsis | 0/307 (0%) | 0 | 1/306 (0.3%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Epiphyseal fracture | 1/307 (0.3%) | 1 | 0/306 (0%) | 0 |
| Femoral neck fracture | 1/307 (0.3%) | 1 | 1/306 (0.3%) | 1 |
| Joint dislocation | 0/307 (0%) | 0 | 1/306 (0.3%) | 1 |
| Joint injury | 0/307 (0%) | 0 | 1/306 (0.3%) | 1 |
| Procedural haemorrhage | 1/307 (0.3%) | 1 | 0/306 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Haemarthrosis | 0/307 (0%) | 0 | 1/306 (0.3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Adenocarcinoma of colon | 0/307 (0%) | 0 | 1/306 (0.3%) | 1 |
| Basal cell carcinoma | 0/307 (0%) | 0 | 1/306 (0.3%) | 1 |
| Nervous system disorders | ||||
| Cerebral ischaemia | 1/307 (0.3%) | 1 | 0/306 (0%) | 0 |
| Ischaemic stroke | 1/307 (0.3%) | 1 | 0/306 (0%) | 0 |
| Paraesthesia | 0/307 (0%) | 0 | 1/306 (0.3%) | 1 |
| Partial seizures | 0/307 (0%) | 0 | 1/306 (0.3%) | 1 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 0/307 (0%) | 0 | 1/306 (0.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Sitagliptin | Dapagliflozin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 22/307 (7.2%) | 21/306 (6.9%) | ||
| Metabolism and nutrition disorders | ||||
| Hypoglycaemia | 22/307 (7.2%) | 51 | 21/306 (6.9%) | 64 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
- 0431-838
- 2014-005525-13
- MK-0431-838