Trial Outcomes & Findings for A Study to Test the Safety and Efficacy of Sitagliptin Compared to Glimepiride in Patients With Type 2 Diabetes on a Stable Dose of Metformin (0431-803)(COMPLETED) (NCT NCT00701090)

Last Updated: 2017-03-10

Results Overview

Patient-level HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 30 HbA1c percent minus the Week 0 HbA1c percent.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1035 participants

Primary outcome timeframe

Week 0 to Week 30

Results posted on

2017-03-10

Participant Flow

Phase III First Patient In: 14-May-2008; Last Patient Last Visit: 27-Oct-2009; 109 study centers worldwide

Patients at least 18 years of age with type 2 diabetes mellitus with inadequate glycemic control (A1C ≥6.5 and ≤9.0%) on a stable dose of metformin (at a dose of at least 1500 mg per day for at least 12 weeks) were eligible to enter the 30 week study. Up to a 2 week screening period, followed by a 2-week placebo run-in.

Participant milestones

Participant milestones
Measure	Sitagliptin 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 open-label metformin oral tablets (≥1500 mg/day).	Glimepiride The Glimepiride group includes data from patients randomized to receive treatment starting with 1 mg oral tablets of glimepiride (blinded) up-titrated until Week 18 as needed to a maximum dose of 6 mg q.d. in addition to ongoing treatment with open-label metformin oral tablets (≥1500 mg/day).
Overall Study STARTED	516	519
Overall Study COMPLETED	468	468
Overall Study NOT COMPLETED	48	51

Reasons for withdrawal

Reasons for withdrawal
Measure	Sitagliptin 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 open-label metformin oral tablets (≥1500 mg/day).	Glimepiride The Glimepiride group includes data from patients randomized to receive treatment starting with 1 mg oral tablets of glimepiride (blinded) up-titrated until Week 18 as needed to a maximum dose of 6 mg q.d. in addition to ongoing treatment with open-label metformin oral tablets (≥1500 mg/day).
Overall Study Adverse Event	11	2
Overall Study Death	0	1
Overall Study Lack of Efficacy	5	4
Overall Study Lost to Follow-up	9	9
Overall Study Physician Decision	3	4
Overall Study Protocol Violation	2	3
Overall Study Withdrawal by Subject	11	16
Overall Study Other	7	12

Baseline Characteristics

A Study to Test the Safety and Efficacy of Sitagliptin Compared to Glimepiride in Patients With Type 2 Diabetes on a Stable Dose of Metformin (0431-803)(COMPLETED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sitagliptin n=516 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 open-label metformin oral tablets (≥1500 mg/day).	Glimepiride n=519 Participants The Glimepiride group includes data from patients randomized to receive treatment starting with 1 mg oral tablets of glimepiride (blinded) up-titrated until Week 18 as needed to a maximum dose of 6 mg q.d. in addition to ongoing treatment with open-label metformin oral tablets (≥1500 mg/day).	Total n=1035 Participants Total of all reporting groups
Age, Continuous	56.3 years STANDARD_DEVIATION 9.7 • n=93 Participants	56.2 years STANDARD_DEVIATION 10.1 • n=4 Participants	56.3 years STANDARD_DEVIATION 9.9 • n=27 Participants
Sex: Female, Male Female	232 Participants n=93 Participants	240 Participants n=4 Participants	472 Participants n=27 Participants
Sex: Female, Male Male	284 Participants n=93 Participants	279 Participants n=4 Participants	563 Participants n=27 Participants
Race/Ethnicity, Customized White	297 participants n=93 Participants	298 participants n=4 Participants	595 participants n=27 Participants
Race/Ethnicity, Customized Black	6 participants n=93 Participants	6 participants n=4 Participants	12 participants n=27 Participants
Race/Ethnicity, Customized Asian	109 participants n=93 Participants	111 participants n=4 Participants	220 participants n=27 Participants
Race/Ethnicity, Customized American Indian/Alaska Native	25 participants n=93 Participants	26 participants n=4 Participants	51 participants n=27 Participants
Race/Ethnicity, Customized Other	79 participants n=93 Participants	78 participants n=4 Participants	157 participants n=27 Participants
A1C (Hemoglobin A1c)	7.50 Percent STANDARD_DEVIATION 0.70 • n=93 Participants	7.51 Percent STANDARD_DEVIATION 0.76 • n=4 Participants	7.50 Percent STANDARD_DEVIATION 0.73 • n=27 Participants

PRIMARY outcome

Timeframe: Week 0 to Week 30

Population: The per protocol population included all patients with a baseline value, a measurement at Week 30, and no major protocol violations (i.e., drug compliance \<85%, use of prohibited medications, change of Metformin dose, incorrect double-blind study medication).

Patient-level HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 30 HbA1c percent minus the Week 0 HbA1c percent.

Outcome measures

Outcome measures
Measure	Sitagliptin n=443 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 open-label metformin oral tablets (≥1500 mg/day).	Glimepiride n=436 Participants The Glimepiride group includes data from patients randomized to receive treatment starting with 1 mg oral tablets of glimepiride (blinded) up-titrated until Week 18 as needed to a maximum dose of 6 mg q.d. in addition to ongoing treatment with open-label metformin oral tablets (≥1500 mg/day).
Change From Baseline in HbA1c at Week 30	-0.47 Percent Interval -0.55 to -0.39	-0.54 Percent Interval -0.62 to -0.45

SECONDARY outcome

Timeframe: Week 0 to Week 30

Change from baseline at Week 30 was defined as Week 30 minus Week 0.

Outcome measures

Outcome measures
Measure	Sitagliptin n=446 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 open-label metformin oral tablets (≥1500 mg/day).	Glimepiride n=444 Participants The Glimepiride group includes data from patients randomized to receive treatment starting with 1 mg oral tablets of glimepiride (blinded) up-titrated until Week 18 as needed to a maximum dose of 6 mg q.d. in addition to ongoing treatment with open-label metformin oral tablets (≥1500 mg/day).
Change From Baseline in FPG (Fasting Plasma Glucose) at Week 30	-14.6 mg/dL Interval -17.9 to -11.2	-17.5 mg/dL Interval -20.8 to -14.1

SECONDARY outcome

Timeframe: Week 0 to Week 30

Population: All patients who took at least one dose of study therapy.

Outcome measures

Outcome measures
Measure	Sitagliptin n=516 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 open-label metformin oral tablets (≥1500 mg/day).	Glimepiride n=518 Participants The Glimepiride group includes data from patients randomized to receive treatment starting with 1 mg oral tablets of glimepiride (blinded) up-titrated until Week 18 as needed to a maximum dose of 6 mg q.d. in addition to ongoing treatment with open-label metformin oral tablets (≥1500 mg/day).
Percent of Patients With at Least One Hypoglycemia Episode of Any Type at Week 30	7.0 Percentage of Participants	22.0 Percentage of Participants

SECONDARY outcome

Timeframe: Week 0 to Week 30

Population: All patients who took at least one dose of study therapy and had body weight measurements at both baseline and Week 30.

Change from baseline at Week 30 was defined as Week 30 minus Week 0.

Outcome measures

Outcome measures
Measure	Sitagliptin n=465 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 open-label metformin oral tablets (≥1500 mg/day).	Glimepiride n=461 Participants The Glimepiride group includes data from patients randomized to receive treatment starting with 1 mg oral tablets of glimepiride (blinded) up-titrated until Week 18 as needed to a maximum dose of 6 mg q.d. in addition to ongoing treatment with open-label metformin oral tablets (≥1500 mg/day).
Change From Baseline in Body Weight at Week 30	-0.8 Kilograms Interval -1.1 to -0.5	1.2 Kilograms Interval 0.9 to 1.5

SECONDARY outcome

Timeframe: Week 30

Outcome measures

Outcome measures
Measure	Sitagliptin n=443 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 open-label metformin oral tablets (≥1500 mg/day).	Glimepiride n=436 Participants The Glimepiride group includes data from patients randomized to receive treatment starting with 1 mg oral tablets of glimepiride (blinded) up-titrated until Week 18 as needed to a maximum dose of 6 mg q.d. in addition to ongoing treatment with open-label metformin oral tablets (≥1500 mg/day).
Percent of Patients With A1C <7.0% at Week 30	52.4 Percentage of Participants	59.6 Percentage of Participants

SECONDARY outcome

Timeframe: Week 30

Outcome measures

Outcome measures
Measure	Sitagliptin n=443 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 open-label metformin oral tablets (≥1500 mg/day).	Glimepiride n=436 Participants The Glimepiride group includes data from patients randomized to receive treatment starting with 1 mg oral tablets of glimepiride (blinded) up-titrated until Week 18 as needed to a maximum dose of 6 mg q.d. in addition to ongoing treatment with open-label metformin oral tablets (≥1500 mg/day).
Percent of Patients With A1C <6.5% at Week 30	21.2 Percentage of Participants	27.5 Percentage of Participants

Adverse Events

Sitagliptin

Serious events: 16 serious events

Other events: 58 other events

Deaths: 0 deaths

Glimepiride

Serious events: 11 serious events

Other events: 134 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Sitagliptin n=519 participants at risk；n=516 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 open-label metformin oral tablets (≥1500 mg/day).	Glimepiride n=518 participants at risk The Glimepiride group includes data from patients randomized to receive treatment starting with 1 mg oral tablets of glimepiride (blinded) up-titrated until Week 18 as needed to a maximum dose of 6 mg q.d. in addition to ongoing treatment with open-label metformin oral tablets (≥1500 mg/day).
Infections and infestations Nasopharyngitis	4.8% 25/519 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	6.9% 36/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Metabolism and nutrition disorders Hypoglycaemia	6.9% 36/519 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	22.0% 114/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.

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

Measure	Sitagliptin n=519 participants at risk；n=516 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 open-label metformin oral tablets (≥1500 mg/day).	Glimepiride n=518 participants at risk The Glimepiride group includes data from patients randomized to receive treatment starting with 1 mg oral tablets of glimepiride (blinded) up-titrated until Week 18 as needed to a maximum dose of 6 mg q.d. in addition to ongoing treatment with open-label metformin oral tablets (≥1500 mg/day).
Blood and lymphatic system disorders Thrombocytopenia	0.19% 1/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.00% 0/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Cardiac disorders Acute coronary syndrome	0.00% 0/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.19% 1/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Cardiac disorders Coronary artery disease	0.00% 0/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.19% 1/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Cardiac disorders Myocardial ischaemia	0.39% 2/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.00% 0/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Gastrointestinal disorders Inguinal hernia	0.19% 1/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.00% 0/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
General disorders Non-cardiac chest pain	0.00% 0/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.19% 1/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
General disorders Pain	0.00% 0/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.19% 1/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Infections and infestations Anal abscess	0.00% 0/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.19% 1/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Infections and infestations Infection	0.00% 0/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.19% 1/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Infections and infestations Mastitis	0.19% 1/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.00% 0/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Infections and infestations Peritonsillar abscess	0.19% 1/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.00% 0/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Infections and infestations Pneumonia	0.00% 0/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.19% 1/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Infections and infestations Typhoid fever	0.19% 1/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.00% 0/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Injury, poisoning and procedural complications Clavicle fracture	0.00% 0/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.19% 1/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Injury, poisoning and procedural complications Humerus fracture	0.19% 1/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.00% 0/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Injury, poisoning and procedural complications Patella fracture	0.19% 1/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.00% 0/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Injury, poisoning and procedural complications Skin laceration	0.19% 1/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.00% 0/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.19% 1/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.00% 0/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.19% 1/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.19% 1/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.19% 1/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung squamous cell carcinoma stage unspecified	0.19% 1/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.00% 0/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.19% 1/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.00% 0/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Nervous system disorders Autonomic neuropathy	0.19% 1/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.00% 0/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Nervous system disorders Cerebrovascular accident	0.00% 0/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.19% 1/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Nervous system disorders Haemorrhagic stroke	0.00% 0/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.19% 1/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Nervous system disorders Syncope	0.00% 0/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.19% 1/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Respiratory, thoracic and mediastinal disorders Prostatitis	0.19% 1/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.00% 0/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.
Vascular disorders Hypertension	0.19% 1/516 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.	0.00% 0/518 Particpants analyzed are those who received at least 1 dose of study medication. One participant in the Glimepiride group did not receive any study medication and is not included in the analysis.