Trial Outcomes & Findings for Addition Of Januvia (Sitagliptin) Improves Glycemic Control In Patients Inadequately Controlled By Metformin (MK0431-078) (NCT NCT00545584)

Last Updated: 2017-05-12

Results Overview

Hemoglobin A1c (HbA1c) is a measure of glycated hemoglobin in the blood. HbA1c greater than 6.5% was considered inadequately controlled.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1512 participants

Primary outcome timeframe

Baseline and Week 24

Results posted on

2017-05-12

Participant Flow

1512 subjects were selected/screened, 380 subjects failed screening, leaving 1132 subjects who were randomized.

Participant milestones

Participant milestones
Measure	Sitagliptin With Standard of Care Subjects received sitagliptin 100 mg once daily for 26 Weeks, and: No specific intervention (standard recommendation) on physical exercise and diet.	Sitagliptin With Diet Advice Subjects received sitagliptin 100 mg once daily for 26 Weeks, and: Intervention on diet which includes advice on diet with a leaflet and a diary	Sitagliptin With Diet and Physical Activity Advice Subjects received sitagliptin 100 mg once daily for 26 Weeks, and: Intervention on diet + physical activity which includes advice on diet and physical activity with leaflets and diaries PLUS advice on physical activity with the utilization of a pedometer: subjects were asked to walk 10,000 steps per day 5 or more days per week.
Overall Study STARTED	412	414	306
Overall Study COMPLETED	333	334	250
Overall Study NOT COMPLETED	79	80	56

Reasons for withdrawal

Reasons for withdrawal
Measure	Sitagliptin With Standard of Care Subjects received sitagliptin 100 mg once daily for 26 Weeks, and: No specific intervention (standard recommendation) on physical exercise and diet.	Sitagliptin With Diet Advice Subjects received sitagliptin 100 mg once daily for 26 Weeks, and: Intervention on diet which includes advice on diet with a leaflet and a diary	Sitagliptin With Diet and Physical Activity Advice Subjects received sitagliptin 100 mg once daily for 26 Weeks, and: Intervention on diet + physical activity which includes advice on diet and physical activity with leaflets and diaries PLUS advice on physical activity with the utilization of a pedometer: subjects were asked to walk 10,000 steps per day 5 or more days per week.
Overall Study Only one reason for discontinuation	62	61	48
Overall Study Two or more reasons for discontinuation	17	19	8

Baseline Characteristics

Addition Of Januvia (Sitagliptin) Improves Glycemic Control In Patients Inadequately Controlled By Metformin (MK0431-078)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sitagliptin With Standard of Care n=362 Participants Subjects received sitagliptin 100 mg once daily for 26 Weeks, and: No specific intervention (standard recommendation) on physical exercise and diet.	Sitagliptin With Diet Advice n=358 Participants Subjects received sitagliptin 100 mg once daily for 26 Weeks, and: Intervention on diet which includes advice on diet with a leaflet and a diary	Sitagliptin With Diet and Physical Activity Advice n=265 Participants Subjects received sitagliptin 100 mg once daily for 26 Weeks, and: Intervention on diet + physical activity which includes advice on diet and physical activity with leaflets and diaries PLUS advice on physical activity with the utilization of a pedometer: subjects were asked to walk 10,000 steps per day 5 or more days per week.	Total n=985 Participants Total of all reporting groups
Age, Continuous	58.26 years STANDARD_DEVIATION 10.04 • n=5 Participants	57.47 years STANDARD_DEVIATION 9.12 • n=7 Participants	57.30 years STANDARD_DEVIATION 9.90 • n=5 Participants	57.71 years STANDARD_DEVIATION 9.68 • n=4 Participants
Sex: Female, Male Female	181 Participants n=5 Participants	175 Participants n=7 Participants	126 Participants n=5 Participants	482 Participants n=4 Participants
Sex: Female, Male Male	181 Participants n=5 Participants	183 Participants n=7 Participants	139 Participants n=5 Participants	503 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: The Full Analysis Set (FAS) population included all selected patients with at least one measured HbA1c value after Visit 2 and having received at least one dose of sitagliptin. In the Standard of Care group, only 360 subjects had HbA1c Baseline evaluations.

Hemoglobin A1c (HbA1c) is a measure of glycated hemoglobin in the blood. HbA1c greater than 6.5% was considered inadequately controlled.

Outcome measures

Outcome measures
Measure	Sitagliptin With Standard of Care n=362 Participants Subjects received sitagliptin 100 mg once daily for 26 Weeks, and: No specific intervention (standard recommendation) on physical exercise and diet.	Sitagliptin With Diet Advice n=358 Participants Subjects received sitagliptin 100 mg once daily for 26 Weeks, and: Intervention on diet which includes advice on diet with a leaflet and a diary	Sitagliptin With Diet and Physical Activity Advice n=265 Participants Subjects received sitagliptin 100 mg once daily for 26 Weeks, and: Intervention on diet + physical activity which includes advice on diet and physical activity with leaflets and diaries PLUS advice on physical activity with the utilization of a pedometer: subjects were asked to walk 10,000 steps per day 5 or more days per week.
Hemoglobin A1c Measurement Baseline (n=360, 358, and 265, respectively)	7.37 percent HbA1c Standard Deviation 0.61	7.50 percent HbA1c Standard Deviation 0.66	7.49 percent HbA1c Standard Deviation 0.60
Hemoglobin A1c Measurement Week 24 (n=362, 358, and 265, respectively)	7.33 percent HbA1c Standard Deviation 1.09	7.42 percent HbA1c Standard Deviation 1.15	7.40 percent HbA1c Standard Deviation 1.07

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: FAS population. Furthermore, only 350, 252, and 350 subjects had FPG evaluations in the Diet advice, Diet \& physical activity advice, and Standard groups, respectively, at Baseline; and 303, 224, and 310 subjects had FPG evaluations in the Diet advice, Diet \& physical activity advice, and Standard groups, respectively, at Week 24.

Generally FPG values of \~5.0-7.2 mmol/L would be considered goal (American Diabetes Association).

Outcome measures

Outcome measures
Measure	Sitagliptin With Standard of Care n=310 Participants Subjects received sitagliptin 100 mg once daily for 26 Weeks, and: No specific intervention (standard recommendation) on physical exercise and diet.	Sitagliptin With Diet Advice n=303 Participants Subjects received sitagliptin 100 mg once daily for 26 Weeks, and: Intervention on diet which includes advice on diet with a leaflet and a diary	Sitagliptin With Diet and Physical Activity Advice n=224 Participants Subjects received sitagliptin 100 mg once daily for 26 Weeks, and: Intervention on diet + physical activity which includes advice on diet and physical activity with leaflets and diaries PLUS advice on physical activity with the utilization of a pedometer: subjects were asked to walk 10,000 steps per day 5 or more days per week.
Fasting Plasma Glucose (FPG) Measurement Baseline (n=350, 350, 252, respectively)	8.87 mmol/L glucose Standard Deviation 1.98	9.00 mmol/L glucose Standard Deviation 2.03	8.91 mmol/L glucose Standard Deviation 1.87
Fasting Plasma Glucose (FPG) Measurement Week 24 (n=310, 303, and 224, respectively)	8.21 mmol/L glucose Standard Deviation 2.07	8.32 mmol/L glucose Standard Deviation 2.08	8.47 mmol/L glucose Standard Deviation 2.17

Adverse Events

Sitagliptin With Standard of Care

Serious events: 8 serious events

Other events: 0 other events

Deaths: 0 deaths

Sitagliptin With Diet Advice

Serious events: 18 serious events

Other events: 0 other events

Deaths: 0 deaths

Sitagliptin With Diet and Physical Activity Advice

Serious events: 7 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

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 With Standard of Care n=412 participants at risk Subjects received sitagliptin 100 mg once daily for 26 Weeks, and: No specific intervention (standard recommendation) on physical exercise and diet.	Sitagliptin With Diet Advice n=414 participants at risk Subjects received sitagliptin 100 mg once daily for 26 Weeks, and: Intervention on diet which includes advice on diet with a leaflet and a diary	Sitagliptin With Diet and Physical Activity Advice n=305 participants at risk Subjects received sitagliptin 100 mg once daily for 26 Weeks, and: Intervention on diet + physical activity which includes advice on diet and physical activity with leaflets and diaries PLUS advice on physical activity with the utilization of a pedometer: subjects were asked to walk 10,000 steps per day 5 or more days per week.
Blood and lymphatic system disorders IDIOPATHIC THROMBOCYTOPENIC PURPURA	0.24% 1/412 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/414 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Cardiac disorders ACUTE CORONARY SYNDROME	0.24% 1/412 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.24% 1/414 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Cardiac disorders ADAMS-STOKES SYNDROME	0.24% 1/412 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/414 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Cardiac disorders ANGINA UNSTABLE	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.24% 1/414 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Cardiac disorders MYOCARDIAL INFARCTION	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.24% 1/414 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Eye disorders MACULAR OPACITY	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.24% 1/414 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Gastrointestinal disorders INGUINAL HERNIA	0.24% 1/412 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/414 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
General disorders CARDIAC DEATH	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.24% 1/414 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
General disorders SUDDEN DEATH	0.24% 1/412 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/414 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Hepatobiliary disorders CHOLECYSTITIS	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.24% 1/414 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Infections and infestations ABDOMINAL WALL ABSCESS	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.24% 1/414 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Infections and infestations EAR INFECTION	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.24% 1/414 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Infections and infestations LARYNGITIS	0.24% 1/412 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/414 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Infections and infestations PNEUMONIA	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.24% 1/414 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Injury, poisoning and procedural complications DRUG EXPOSURE DURING PREGNANCY	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.24% 1/414 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Injury, poisoning and procedural complications FRACTURE	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/414 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.33% 1/305 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Injury, poisoning and procedural complications LIMB TRAUMATIC AMPUTATION	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.24% 1/414 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Injury, poisoning and procedural complications LUMBAR VERTEBRAL FRACTURE	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.24% 1/414 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Injury, poisoning and procedural complications TENDON RUPTURE	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.24% 1/414 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Metabolism and nutrition disorders DIABETES MELLITUS	0.24% 1/412 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/414 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Musculoskeletal and connective tissue disorders OSTEOARTHRITIS	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/414 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.33% 1/305 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BREAST CANCER	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.24% 1/414 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) FIBROMA	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.24% 1/414 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) LUNG NEOPLASM MALIGNANT	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/414 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.33% 1/305 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) PROSTATE CANCER	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/414 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.66% 2/305 • Number of events 2 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Nervous system disorders CERVICAL ROOT PAIN	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/414 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.33% 1/305 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Nervous system disorders ENCEPHALITIS	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.24% 1/414 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Nervous system disorders SCIATICA	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/414 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.33% 1/305 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Nervous system disorders SYNCOPE	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.24% 1/414 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Psychiatric disorders DEPRESSION	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.24% 1/414 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Psychiatric disorders SUICIDE ATTEMPT	0.24% 1/412 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/414 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Renal and urinary disorders RENAL NECROSIS	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.24% 1/414 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Reproductive system and breast disorders GENITAL PROLAPSE	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.24% 1/414 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Respiratory, thoracic and mediastinal disorders PULMONARY EMBOLISM	0.24% 1/412 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/414 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).
Skin and subcutaneous tissue disorders RASH	0.00% 0/412 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.24% 1/414 • Number of events 1 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).	0.00% 0/305 • This safety data includes AEs and SAEs that occurred during treatment (Visit 2 to Visit 4).