Trial Outcomes & Findings for Sitagliptin Metformin Add-on Study in Patients With Type 2 Diabetes Mellitus (NCT NCT00337610)

NCT ID: NCT00337610

Last Updated: 2016-05-12

Results Overview

A1C was measured as a percent. Thus, this change from baseline reflects the Week 18 A1C percent minus the Week 0 A1C percent.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

190 participants

Primary outcome timeframe

Baseline and Week 18

Results posted on

2016-05-12

Participant Flow

First Patient In: 21-Aug-2006; Last Patient Last Visit: 15-Aug-2007; Twenty-four medical clinics worldwide (12 in the United States, 2 in Israel, 3 in Mexico, 3 in Peru, and 4 in Austria).

Patients 18-78 years on oral single antihyperglycemic agent (AHA) (hemoglobin A1C \[A1C\] ≥8%) or metformin-based dual combination therapy (A1C 7.5-10.5%) were eligible to participate. Eligible patients underwent an up to 12-week metformin dose-titration/dose-stable period followed by a 2-week placebo run-in period prior to randomization.

Participant milestones

Participant milestones
Measure
Sitagliptin 100 mg
The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily in addition to ongoing treatment with open-label metformin ≥ 1500 mg/day.
Placebo
The Placebo group includes data from patients randomized to receive treatment with oral tablets of sitagliptin-matching placebo once daily in addition to ongoing treatment with open-label metformin ≥ 1500 mg/day.
Overall Study
STARTED
96
94
Overall Study
Completed Week 18
89
82
Overall Study
COMPLETED
79
80
Overall Study
NOT COMPLETED
17
14

Reasons for withdrawal

Reasons for withdrawal
Measure
Sitagliptin 100 mg
The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily in addition to ongoing treatment with open-label metformin ≥ 1500 mg/day.
Placebo
The Placebo group includes data from patients randomized to receive treatment with oral tablets of sitagliptin-matching placebo once daily in addition to ongoing treatment with open-label metformin ≥ 1500 mg/day.
Overall Study
Adverse Event
2
2
Overall Study
Death
0
1
Overall Study
Lack of Efficacy
6
3
Overall Study
Lost to Follow-up
3
3
Overall Study
Withdrawal by Subject
6
5

Baseline Characteristics

Sitagliptin Metformin Add-on Study in Patients With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Sitagliptin 100 mg
n=96 Participants
The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily in addition to ongoing treatment with open-label metformin ≥ 1500 mg/day.
Placebo
n=94 Participants
The Placebo group includes data from patients randomized to receive treatment with oral tablets of sitagliptin-matching placebo once daily in addition to ongoing treatment with open-label metformin ≥ 1500 mg/day.
Total
n=190 Participants
Total of all reporting groups
Age, Continuous
53.6 years
STANDARD_DEVIATION 9.5 • n=5 Participants
56.1 years
STANDARD_DEVIATION 9.5 • n=7 Participants
54.8 years
STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male
Female
47 Participants
n=5 Participants
55 Participants
n=7 Participants
102 Participants
n=5 Participants
Sex: Female, Male
Male
49 Participants
n=5 Participants
39 Participants
n=7 Participants
88 Participants
n=5 Participants
Race/Ethnicity, Customized
White
40 participants
n=5 Participants
44 participants
n=7 Participants
84 participants
n=5 Participants
Race/Ethnicity, Customized
Black
3 participants
n=5 Participants
1 participants
n=7 Participants
4 participants
n=5 Participants
Race/Ethnicity, Customized
Hispanic
31 participants
n=5 Participants
24 participants
n=7 Participants
55 participants
n=5 Participants
Race/Ethnicity, Customized
Asian
1 participants
n=5 Participants
0 participants
n=7 Participants
1 participants
n=5 Participants
Race/Ethnicity, Customized
Other
21 participants
n=5 Participants
25 participants
n=7 Participants
46 participants
n=5 Participants
2-Hour Post-Meal Glucose (2 hr PMG)
288.7 mg/dL
STANDARD_DEVIATION 74.8 • n=5 Participants
286.7 mg/dL
STANDARD_DEVIATION 61.7 • n=7 Participants
287.7 mg/dL
STANDARD_DEVIATION 68.5 • n=5 Participants
Fasting Plasma Glucose (FPG)
201.1 mg/dL
STANDARD_DEVIATION 46.2 • n=5 Participants
198.2 mg/dL
STANDARD_DEVIATION 44.6 • n=7 Participants
199.7 mg/dL
STANDARD_DEVIATION 45.3 • n=5 Participants
Hemoglobin A1C (A1C)
9.3 Percent
STANDARD_DEVIATION 0.9 • n=5 Participants
9.1 Percent
STANDARD_DEVIATION 0.8 • n=7 Participants
9.2 Percent
STANDARD_DEVIATION 0.8 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 18

Population: The full-analysis-set (FAS) population included all patients with at least one dose of double-blind study therapy, and with a baseline value and ≥1 postbaseline value for this outcome. Data following glycemic rescue were treated as missing. Missing data were handled using the last observation carrying forward (LOCF) method.

A1C was measured as a percent. Thus, this change from baseline reflects the Week 18 A1C percent minus the Week 0 A1C percent.

Outcome measures

Outcome measures
Measure
Placebo
n=92 Participants
The Placebo group includes data from patients randomized to receive treatment with oral tablets of sitagliptin-matching placebo once daily in addition to ongoing treatment with open-label metformin ≥ 1500 mg/day.
Sitagliptin 100 mg
n=95 Participants
The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily in addition to ongoing treatment with open-label metformin ≥ 1500 mg/day.
Change From Baseline in A1C at Week 18
0.02 Percent
Interval -0.23 to 0.27
-1.00 Percent
Interval -1.24 to -0.75

SECONDARY outcome

Timeframe: Baseline and Week 18

Population: The full-analysis-set (FAS) population included all patients with at least one dose of double-blind study therapy, and with a baseline value and ≥1 postbaseline value for this outcome. Data following glycemic rescue were treated as missing. Missing data were handled using the LOCF method.

Change from baseline at Week 18 is defined as Week 18 FPG minus Week 0 FPG.

Outcome measures

Outcome measures
Measure
Placebo
n=92 Participants
The Placebo group includes data from patients randomized to receive treatment with oral tablets of sitagliptin-matching placebo once daily in addition to ongoing treatment with open-label metformin ≥ 1500 mg/day.
Sitagliptin 100 mg
n=96 Participants
The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily in addition to ongoing treatment with open-label metformin ≥ 1500 mg/day.
Change From Baseline in FPG at Week 18
-6.5 mg/dL
Interval -15.1 to 2.2
-32.0 mg/dL
Interval -40.6 to -23.3

SECONDARY outcome

Timeframe: Baseline and Week 18

Population: The full-analysis-set (FAS) population included all patients with at least one dose of double-blind study therapy, and with a baseline value and ≥1 postbaseline value for this outcome. Data following glycemic rescue were treated as missing. Missing data were handled using the LOCF method.

Change from baseline at Week 18 is defined as Week 18 minus Week 0.

Outcome measures

Outcome measures
Measure
Placebo
n=74 Participants
The Placebo group includes data from patients randomized to receive treatment with oral tablets of sitagliptin-matching placebo once daily in addition to ongoing treatment with open-label metformin ≥ 1500 mg/day.
Sitagliptin 100 mg
n=79 Participants
The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily in addition to ongoing treatment with open-label metformin ≥ 1500 mg/day.
Change From Baseline in 2 Hr-PMG at Week 18
-13.5 mg/dL
Interval -28.2 to 1.2
-67.6 mg/dL
Interval -82.1 to -53.2

SECONDARY outcome

Timeframe: Baseline and Week 30

Population: The full-analysis-set (FAS) population included all patients with at least one dose of double-blind study therapy, and with a baseline value and ≥1 postbaseline value for this outcome. Data following glycemic rescue were treated as missing. Missing data were handled using the LOCF method.

A1C was measured as a percent. Thus, this change from baseline reflects the Week 30 A1C percent minus the Week 0 A1C percent.

Outcome measures

Outcome measures
Measure
Placebo
n=92 Participants
The Placebo group includes data from patients randomized to receive treatment with oral tablets of sitagliptin-matching placebo once daily in addition to ongoing treatment with open-label metformin ≥ 1500 mg/day.
Sitagliptin 100 mg
n=95 Participants
The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily in addition to ongoing treatment with open-label metformin ≥ 1500 mg/day.
Change From Baseline in A1C at Week 30
0.04 Percent
Interval -0.24 to 0.31
-0.98 Percent
Interval -1.25 to -0.7

Adverse Events

Sitagliptin 100 mg

Serious events: 0 serious events
Other events: 18 other events
Deaths: 0 deaths

Placebo

Serious events: 5 serious events
Other events: 29 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Sitagliptin 100 mg
n=96 participants at risk
The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily in addition to ongoing treatment with open-label metformin ≥ 1500 mg/day.
Placebo
n=94 participants at risk
The Placebo group includes data from patients randomized to receive treatment with oral tablets of sitagliptin-matching placebo once daily in addition to ongoing treatment with open-label metformin ≥ 1500 mg/day.
Cardiac disorders
Myocardial Ischaemia
0.00%
0/96 • Weeks 0 to 30
1.1%
1/94 • Weeks 0 to 30
Gastrointestinal disorders
Upper Gastrointestinal Haemorrhage
0.00%
0/96 • Weeks 0 to 30
1.1%
1/94 • Weeks 0 to 30
Injury, poisoning and procedural complications
Upper Limb Fracture
0.00%
0/96 • Weeks 0 to 30
1.1%
1/94 • Weeks 0 to 30
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma Pancreas
0.00%
0/96 • Weeks 0 to 30
1.1%
1/94 • Weeks 0 to 30
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon Cancer
0.00%
0/96 • Weeks 0 to 30
1.1%
1/94 • Weeks 0 to 30
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphoma
0.00%
0/96 • Weeks 0 to 30
1.1%
1/94 • Weeks 0 to 30

Other adverse events

Other adverse events
Measure
Sitagliptin 100 mg
n=96 participants at risk
The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily in addition to ongoing treatment with open-label metformin ≥ 1500 mg/day.
Placebo
n=94 participants at risk
The Placebo group includes data from patients randomized to receive treatment with oral tablets of sitagliptin-matching placebo once daily in addition to ongoing treatment with open-label metformin ≥ 1500 mg/day.
Gastrointestinal disorders
Diarrhoea
5.2%
5/96 • Weeks 0 to 30
5.3%
5/94 • Weeks 0 to 30
Infections and infestations
Nasopharyngitis
7.3%
7/96 • Weeks 0 to 30
6.4%
6/94 • Weeks 0 to 30
Infections and infestations
Pharyngitis
4.2%
4/96 • Weeks 0 to 30
6.4%
6/94 • Weeks 0 to 30
Investigations
Blood Glucose Increased
6.2%
6/96 • Weeks 0 to 30
18.1%
17/94 • Weeks 0 to 30

Additional Information

Executive Vice President, Clinical and Quantitative Sciences

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

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