Trial Outcomes & Findings for Sitagliptin Added-on to Insulin Study (0431-051) (NCT NCT00395343)
NCT ID: NCT00395343
Last Updated: 2017-05-12
Results Overview
A1C is measured as a percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
641 participants
Primary outcome timeframe
Baseline and Week 24
Results posted on
2017-05-12
Participant Flow
Phase III First Patient In: 29-Jan-2007 Last Patient Last Visit: 13-Oct-2008; 100 study centers worldwide
Patients at least 21 years of age with type 2 diabetes mellitus with inadequate glycemic control (A1C ≥7.5 and ≤11.0%) on stable-dose insulin (alone or in combination with stable-dose metformin) were eligible to enter the 24 week study. 1-week screening, followed by a 2-week single-blind placebo run-in.
Participant milestones
| Measure |
Sitagliptin 100 mg q.d.
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo
The Placebo group includes data from patients randomized to receive treatment with a placebo of the sitagliptin 100 mg oral tablet once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
|---|---|---|
|
Overall Study
STARTED
|
322
|
319
|
|
Overall Study
COMPLETED
|
281
|
283
|
|
Overall Study
NOT COMPLETED
|
41
|
36
|
Reasons for withdrawal
| Measure |
Sitagliptin 100 mg q.d.
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo
The Placebo group includes data from patients randomized to receive treatment with a placebo of the sitagliptin 100 mg oral tablet once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
|---|---|---|
|
Overall Study
Adverse Event
|
13
|
5
|
|
Overall Study
Lack of Efficacy
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
4
|
4
|
|
Overall Study
Physician Decision
|
2
|
4
|
|
Overall Study
Protocol Violation
|
6
|
8
|
|
Overall Study
Withdrawal by Subject
|
11
|
12
|
|
Overall Study
Other
|
5
|
2
|
Baseline Characteristics
Sitagliptin Added-on to Insulin Study (0431-051)
Baseline characteristics by cohort
| Measure |
Sitagliptin 100 mg q.d.
n=322 Participants
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo
n=319 Participants
The Placebo group includes data from patients randomized to receive treatment with a placebo of the sitagliptin 100 mg oral tablet once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Total
n=641 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
58.3 years
STANDARD_DEVIATION 9.1 • n=5 Participants
|
57.2 years
STANDARD_DEVIATION 9.3 • n=7 Participants
|
57.8 years
STANDARD_DEVIATION 9.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
165 Participants
n=5 Participants
|
150 Participants
n=7 Participants
|
315 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
157 Participants
n=5 Participants
|
169 Participants
n=7 Participants
|
326 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
228 participants
n=5 Participants
|
219 participants
n=7 Participants
|
447 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
21 participants
n=5 Participants
|
23 participants
n=7 Participants
|
44 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
55 participants
n=5 Participants
|
61 participants
n=7 Participants
|
116 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
18 participants
n=5 Participants
|
16 participants
n=7 Participants
|
34 participants
n=5 Participants
|
|
A1C (Hemoglobin A1c)
|
8.7 Percent
STANDARD_DEVIATION 0.9 • n=5 Participants
|
8.6 Percent
STANDARD_DEVIATION 0.9 • n=7 Participants
|
8.7 Percent
STANDARD_DEVIATION 0.9 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 24Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 24, the last non-baseline observed measurement was carried forward to Week 24.
A1C is measured as a percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent.
Outcome measures
| Measure |
Sitagliptin 100 mg q.d.
n=305 Participants
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo
n=312 Participants
The Placebo group includes data from patients randomized to receive treatment with a placebo of the sitagliptin 100 mg oral tablet once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
|---|---|---|
|
Change From Baseline in A1C at Week 24
|
-0.59 Percent
Interval -0.7 to -0.48
|
-0.03 Percent
Interval -0.14 to 0.08
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 24, the last non-baseline observed measurement was carried forward to Week 24.
Change from baseline at Week 24 is defined as Week 24 minus Week 0.
Outcome measures
| Measure |
Sitagliptin 100 mg q.d.
n=310 Participants
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo
n=313 Participants
The Placebo group includes data from patients randomized to receive treatment with a placebo of the sitagliptin 100 mg oral tablet once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
|---|---|---|
|
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
|
-18.5 mg/dL
Interval -25.1 to -11.9
|
-3.5 mg/dL
Interval -10.2 to 3.1
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 24, the last non-baseline observed measurement was carried forward to Week 24.
Change from baseline at Week 24 is defined as Week 24 minus Week 0.
Outcome measures
| Measure |
Sitagliptin 100 mg q.d.
n=240 Participants
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo
n=257 Participants
The Placebo group includes data from patients randomized to receive treatment with a placebo of the sitagliptin 100 mg oral tablet once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
|---|---|---|
|
Change From Baseline in 2-hour Post-meal Glucose (PMG) at Week 24
|
-30.9 mg/dL
Interval -40.0 to -21.8
|
5.2 mg/dL
Interval -3.6 to 13.9
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: The Full Analysis Set (FAS) included all patients who participated in the 10-point meal tolerance test and had a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 24, the last non-baseline observed measurement was carried forward to Week 24.
Static sensitivity is a measure of the effect of glucose on beta-cell secretion and is the ratio between the insulin secretion rate and glucose concentration above the threshold level at steady state. (See Breda and Cobelli, Annals of Biomedical Engineering 29, 692-700 (2001) for more details.)
Outcome measures
| Measure |
Sitagliptin 100 mg q.d.
n=35 Participants
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo
n=45 Participants
The Placebo group includes data from patients randomized to receive treatment with a placebo of the sitagliptin 100 mg oral tablet once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
|---|---|---|
|
Percent Change From Baseline in Index of Static Beta-Cell Sensitivity to Glucose at Week 24
|
28.4 Percent
Interval 5.4 to 56.6
|
-8.1 Percent
Interval -22.6 to 9.2
|
SECONDARY outcome
Timeframe: 24 WeeksPopulation: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 24, the last non-baseline observed measurement was carried forward to Week 24.
Outcome measures
| Measure |
Sitagliptin 100 mg q.d.
n=305 Participants
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo
n=312 Participants
The Placebo group includes data from patients randomized to receive treatment with a placebo of the sitagliptin 100 mg oral tablet once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
|---|---|---|
|
Percent of Patients With A1C < 7.0% at Week 24
|
12.8 Percent
|
5.1 Percent
|
SECONDARY outcome
Timeframe: Week 24Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 24, the last non-baseline observed measurement was carried forward to Week 24.
Outcome measures
| Measure |
Sitagliptin 100 mg q.d.
n=305 Participants
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo
n=312 Participants
The Placebo group includes data from patients randomized to receive treatment with a placebo of the sitagliptin 100 mg oral tablet once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
|---|---|---|
|
Percent of Patients With A1C < 6.5% at Week 24
|
2.3 Percent
|
1.9 Percent
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and Week 24Population: The Full Analysis Set (FAS) included the subset of patients on long-acting or intermediate-acting insulin with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 24, the last non-baseline observed measurement was carried forward to Week 24.
A1C in subset of patients on long-acting or intermediate-acting insulin. A1C is measured as a percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent.
Outcome measures
| Measure |
Sitagliptin 100 mg q.d.
n=225 Participants
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo
n=232 Participants
The Placebo group includes data from patients randomized to receive treatment with a placebo of the sitagliptin 100 mg oral tablet once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
|---|---|---|
|
Change From Baseline in A1C at Week 24
|
-0.61 Percent
Interval -0.73 to -0.48
|
-0.04 Percent
Interval -0.16 to 0.08
|
Adverse Events
Sitagliptin 100 mg q.d.
Serious events: 20 serious events
Other events: 49 other events
Deaths: 0 deaths
Placebo
Serious events: 11 serious events
Other events: 25 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Sitagliptin 100 mg q.d.
n=322 participants at risk
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo
n=319 participants at risk
The Placebo group includes data from patients randomized to receive treatment with a placebo of the sitagliptin 100 mg oral tablet once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Any Skin and Subcutaneous Tissue Disorders
|
0.62%
2/322
|
0.00%
0/319
|
|
Skin and subcutaneous tissue disorders
Leukocytoclastic vasculitis
|
0.31%
1/322
|
0.00%
0/319
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.31%
1/322
|
0.00%
0/319
|
|
Vascular disorders
Any Vascular Disorders
|
0.31%
1/322
|
0.00%
0/319
|
|
Vascular disorders
Extremity necrosis
|
0.31%
1/322
|
0.00%
0/319
|
|
Cardiac disorders
Any Cardiac disorders
|
1.2%
4/322
|
1.6%
5/319
|
|
Cardiac disorders
Acute myocardial infarction
|
0.31%
1/322
|
0.31%
1/319
|
|
Cardiac disorders
Angina pectoris
|
0.62%
2/322
|
0.00%
0/319
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/322
|
0.31%
1/319
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/322
|
0.63%
2/319
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/322
|
0.31%
1/319
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/322
|
0.31%
1/319
|
|
Cardiac disorders
Trifascicular block
|
0.31%
1/322
|
0.00%
0/319
|
|
Gastrointestinal disorders
Any Gastrointestinal Disorders
|
0.62%
2/322
|
0.31%
1/319
|
|
Gastrointestinal disorders
Abdominal pain
|
0.31%
1/322
|
0.00%
0/319
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/322
|
0.31%
1/319
|
|
Gastrointestinal disorders
Oesophageal spasm
|
0.31%
1/322
|
0.00%
0/319
|
|
Hepatobiliary disorders
Any Hepatobiliary disorders
|
0.31%
1/322
|
0.31%
1/319
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/322
|
0.31%
1/319
|
|
Hepatobiliary disorders
Cholelithiasis obstructive
|
0.31%
1/322
|
0.00%
0/319
|
|
Infections and infestations
Any Infections and Infestations
|
0.93%
3/322
|
0.31%
1/319
|
|
Infections and infestations
Bronchitis
|
0.31%
1/322
|
0.00%
0/319
|
|
Infections and infestations
Genital abscess
|
0.31%
1/322
|
0.00%
0/319
|
|
Infections and infestations
Perianal abscess
|
0.00%
0/322
|
0.31%
1/319
|
|
Infections and infestations
Pyelonephritis chronic
|
0.31%
1/322
|
0.00%
0/319
|
|
Injury, poisoning and procedural complications
Any Injury, Poisoning and Procedural Complications
|
0.62%
2/322
|
0.31%
1/319
|
|
Injury, poisoning and procedural complications
Incisional hernia
|
0.00%
0/322
|
0.31%
1/319
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
0.31%
1/322
|
0.00%
0/319
|
|
Injury, poisoning and procedural complications
Traumatic ulcer
|
0.31%
1/322
|
0.00%
0/319
|
|
Investigations
Any Investigations
|
0.31%
1/322
|
0.00%
0/319
|
|
Investigations
Blood glucose increased
|
0.31%
1/322
|
0.00%
0/319
|
|
Metabolism and nutrition disorders
Any Metabolism and nutrition disorders
|
0.62%
2/322
|
0.00%
0/319
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.62%
2/322
|
0.00%
0/319
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Any Neoplasms Benign, Malignant and Unspecified (Incl Cysts and Polyps)
|
0.62%
2/322
|
0.00%
0/319
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.31%
1/322
|
0.00%
0/319
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer
|
0.31%
1/322
|
0.00%
0/319
|
|
Nervous system disorders
Any Nervous System Disorders
|
0.00%
0/322
|
0.63%
2/319
|
|
Nervous system disorders
Headache
|
0.00%
0/322
|
0.31%
1/319
|
|
Nervous system disorders
Syncope
|
0.00%
0/322
|
0.31%
1/319
|
|
Psychiatric disorders
Any Psychiatric Disorders
|
0.31%
1/322
|
0.31%
1/319
|
|
Psychiatric disorders
Depression
|
0.00%
0/322
|
0.31%
1/319
|
|
Psychiatric disorders
Major depression
|
0.31%
1/322
|
0.00%
0/319
|
|
Reproductive system and breast disorders
Any Reproductive System and Breast Disorders
|
0.31%
1/322
|
0.00%
0/319
|
|
Reproductive system and breast disorders
Balanoposthitis
|
0.31%
1/322
|
0.00%
0/319
|
|
Respiratory, thoracic and mediastinal disorders
Any Respiratory, Thoracic and Mediastinal Disorders
|
0.00%
0/322
|
0.31%
1/319
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/322
|
0.31%
1/319
|
Other adverse events
| Measure |
Sitagliptin 100 mg q.d.
n=322 participants at risk
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo
n=319 participants at risk
The Placebo group includes data from patients randomized to receive treatment with a placebo of the sitagliptin 100 mg oral tablet once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
|---|---|---|
|
Metabolism and nutrition disorders
Any Metabolism and nutrition disorders
|
15.2%
49/322
|
7.8%
25/319
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
15.2%
49/322
|
7.8%
25/319
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER