Trial Outcomes & Findings for Safety and Efficacy of Sitagliptin Compared With Glimepiride in Elderly Participants With Type 2 Diabetes Mellitus (MK-0431-251) (NCT NCT01189890)

Last Updated: 2017-06-05

Results Overview

Participant whole blood samples were collected at baseline and Week 30 to determine the LS mean HbA1c change from baseline. HbA1c is a measure of the percentage of glycated hemoglobin in the blood and provides an indication of participant blood glucose control in the 2 to 3 months prior to the evaluation.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

480 participants

Primary outcome timeframe

Baseline and Week 30

Results posted on

2017-06-05

Participant Flow

Participant milestones

Participant milestones
Measure	Sitagliptin Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD	Glimepiride Glimepiride 1-6 mg QD
Overall Study STARTED	241	239
Overall Study COMPLETED	204	200
Overall Study NOT COMPLETED	37	39

Reasons for withdrawal

Reasons for withdrawal
Measure	Sitagliptin Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD	Glimepiride Glimepiride 1-6 mg QD
Overall Study Adverse Event	3	4
Overall Study Lack of Efficacy	7	2
Overall Study Lost to Follow-up	1	7
Overall Study Protocol Violation	1	5
Overall Study Withdrawal by Subject	15	11
Overall Study Non Compliance	0	1
Overall Study Physician Decision	5	4
Overall Study Hyperglycemia Discontinuation Criteria	5	5

Baseline Characteristics

Safety and Efficacy of Sitagliptin Compared With Glimepiride in Elderly Participants With Type 2 Diabetes Mellitus (MK-0431-251)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sitagliptin n=241 Participants Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD	Glimepiride n=239 Participants Glimepiride 1-6 mg QD	Total n=480 Participants Total of all reporting groups
Age, Continuous	70.7 years STANDARD_DEVIATION 4.8 • n=5 Participants	70.8 years STANDARD_DEVIATION 4.9 • n=7 Participants	70.7 years STANDARD_DEVIATION 4.8 • n=5 Participants
Sex: Female, Male Female	130 Participants n=5 Participants	148 Participants n=7 Participants	278 Participants n=5 Participants
Sex: Female, Male Male	111 Participants n=5 Participants	91 Participants n=7 Participants	202 Participants n=5 Participants
Hemoglobin A1c (HbA1c)	7.78 Percentage of HbA1c STANDARD_DEVIATION 0.70 • n=5 Participants	7.78 Percentage of HbA1c STANDARD_DEVIATION 0.67 • n=7 Participants	7.78 Percentage of HbA1c STANDARD_DEVIATION 0.69 • n=5 Participants
Fasting Plasma Glucose (FPG)	168.4 mg/dL STANDARD_DEVIATION 31.2 • n=5 Participants	169.7 mg/dL STANDARD_DEVIATION 35.5 • n=7 Participants	169.0 mg/dL STANDARD_DEVIATION 33.3 • n=5 Participants
Body Weight	76.9 kg STANDARD_DEVIATION 15.1 • n=5 Participants	75.4 kg STANDARD_DEVIATION 16.4 • n=7 Participants	76.0 kg STANDARD_DEVIATION 15.6 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 30

Population: The population included all randomized participants who had a baseline HbA1c, had a HbA1c at Week 30, did not take prohibited concomitant medications, had compliance \>85%, and did not receive any incorrect study medication.

Outcome measures

Outcome measures
Measure	Sitagliptin n=197 Participants Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD	Glimepiride n=191 Participants Glimepiride 1-6 mg QD
Least Squares (LS) Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 30	-0.32 Percentage of HbA1c 95% Confidence Interval 0.78 • Interval -0.51 to -0.14	-0.51 Percentage of HbA1c 95% Confidence Interval 0.89 • Interval -0.69 to -0.33

PRIMARY outcome

Timeframe: Up to Week 30

Population: All randomized participants who received at least one dose of study treatment.

Symptomatic hypoglycemia was defined as an episode with clinical symptoms attributed to hypoglycemia, without regard to glucose level. Participants were instructed to complete the Hypoglycemia Assessment Log (HAL) for any symptomatic episodes he or she believed represent hypoglycemia. If a fingerstick glucose was obtained before or shortly (i.e., within a few minutes) after treating, the value was recorded in the HAL. In addition, participants were instructed to record in the HAL any fingerstick glucose values ≤70 mg/dL (≤3.9 mmol/L) regardless of the presence of clinical symptoms.

Outcome measures

Outcome measures
Measure	Sitagliptin n=241 Participants Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD	Glimepiride n=236 Participants Glimepiride 1-6 mg QD
Number of Participants With an Adverse Event of Symptomatic Hypoglycemia Up to Week 30	2 Participants	11 Participants

PRIMARY outcome

Timeframe: Up to Week 30

Population: All randomized participants who received at least one dose of study treatment.

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of the treatment administered.

Outcome measures

Outcome measures
Measure	Sitagliptin n=241 Participants Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD	Glimepiride n=236 Participants Glimepiride 1-6 mg QD
Number of Participants Experiencing An Adverse Event (AE)	118 Participants	115 Participants

PRIMARY outcome

Timeframe: Up to Week 30

Population: All randomized participants who received at least one dose of study treatment.

Outcome measures

Outcome measures
Measure	Sitagliptin n=241 Participants Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD	Glimepiride n=236 Participants Glimepiride 1-6 mg QD
Number of Participants Discontinuing Study Treatment Due to An AE	3 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline and Week 30

Population: The population included all randomized participants who had a FPG value at baseline and Week 30, did not take prohibited concomitant medications, had compliance \>85%, and did not receive any incorrect study medication.

Plasma samples were collected from participants after an overnight fast at baseline and Week 30 to determine the mean change from baseline in participant FPG.

Outcome measures

Outcome measures
Measure	Sitagliptin n=194 Participants Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD	Glimepiride n=191 Participants Glimepiride 1-6 mg QD
LS Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30	-14.5 mg/dL 95% Confidence Interval 39.0 • Interval -21.6 to -7.4	-21.2 mg/dL 95% Confidence Interval 39.1 • Interval -28.3 to -14.0

SECONDARY outcome

Timeframe: Week 30

Population: The population included all randomized participants who had HbA1c at baseline and Week 30, did not take prohibited concomitant medications, had compliance \>85%, and did not receive any incorrect study medication.

Participant whole blood samples were collected at Week 30 to determine the number of participants achieving HbA1c \<7.0% at Week 30. HbA1c is a measure of the percentage of glycated hemoglobin in the blood and provides an indication of participant blood glucose control in the 2 to 3 months prior to the evaluation.

Outcome measures

Outcome measures
Measure	Sitagliptin n=197 Participants Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD	Glimepiride n=191 Participants Glimepiride 1-6 mg QD
Percentage of Participants With HbA1c <7.0% at Week 30	33.5 Percentage of Participants	46.6 Percentage of Participants

SECONDARY outcome

Timeframe: Week 30

Participant whole blood samples were collected at Week 30 to determine the number of participants achieving HbA1c \<6.5% at Week 30. Hemoglobin A1c is a measure of the percentage of glycated hemoglobin in the blood and provides an indication of participant blood glucose control in the 2 to 3 months prior to the evaluation.

Outcome measures

Outcome measures
Measure	Sitagliptin n=197 Participants Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD	Glimepiride n=191 Participants Glimepiride 1-6 mg QD
Percentage of Participants With HbA1c <6.5% at Week 30	9.1 Percentage of Participants	20.9 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline and Week 30

Population: All randomized participants who received at least one dose of study treatment and had body weight measurements at baseline and at Week 30.

Participants were only permitted to wear a drape gown and undergarments (no street clothes, no shoes or socks) for this evaluation. Body weight was measured after voiding (to the nearest 0.1 kg) and measurements were collected until 2 consecutive measurements did not differ by more than 0.2 kg from each other. Body weight measurements were evaluated using a standardized, calibrated digital scale and was reported in kilograms (kg) at baseline and Week 30.

Outcome measures

Outcome measures
Measure	Sitagliptin n=205 Participants Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD	Glimepiride n=203 Participants Glimepiride 1-6 mg QD
LS Mean Change From Baseline in Participant Body Weight at Week 30	0.4 kg 95% Confidence Interval 3.2 • Interval -0.2 to 1.0	1.1 kg 95% Confidence Interval 2.8 • Interval 0.5 to 1.7

Adverse Events

Sitagliptin

Serious events: 7 serious events

Other events: 34 other events

Deaths: 0 deaths

Glimepiride

Serious events: 6 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sitagliptin n=241 participants at risk Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD	Glimepiride n=236 participants at risk Glimepiride 1-6 mg QD
Blood and lymphatic system disorders Anaemia	0.00% 0/241 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.42% 1/236 • Number of events 1 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.
Cardiac disorders Angina Unstable	0.00% 0/241 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.42% 1/236 • Number of events 1 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.
Cardiac disorders Atrial Fibrillation	0.41% 1/241 • Number of events 1 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/236 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.
Cardiac disorders Cardiac Failure Chronic	0.00% 0/241 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.42% 1/236 • Number of events 1 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.
Gastrointestinal disorders Gastrointestinal Haemorrhage	0.00% 0/241 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.42% 1/236 • Number of events 1 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.
Gastrointestinal disorders Inguinal Hernia	0.41% 1/241 • Number of events 1 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/236 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.
Gastrointestinal disorders Lower Gastrointestinal Haemorrhage	0.41% 1/241 • Number of events 1 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/236 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.
Infections and infestations Gastroenteritis	0.41% 1/241 • Number of events 1 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/236 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon Cancer	0.41% 1/241 • Number of events 1 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/236 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant Melanoma	0.41% 1/241 • Number of events 1 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/236 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate Cancer	0.41% 1/241 • Number of events 1 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/236 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.
Nervous system disorders Nerve Compression	0.00% 0/241 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.42% 1/236 • Number of events 1 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.
Nervous system disorders Syncope	0.00% 0/241 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.42% 1/236 • Number of events 1 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.00% 0/241 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.42% 1/236 • Number of events 1 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.

Other adverse events

Other adverse events
Measure	Sitagliptin n=241 participants at risk Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD	Glimepiride n=236 participants at risk Glimepiride 1-6 mg QD
Infections and infestations Nasopharyngitis	7.5% 18/241 • Number of events 20 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.	8.1% 19/236 • Number of events 21 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hyperglycaemia	5.8% 14/241 • Number of events 17 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.	3.8% 9/236 • Number of events 15 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hypoglycaemia	1.2% 3/241 • Number of events 3 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.	6.4% 15/236 • Number of events 45 • Up to Week 32. The safety population consisted of all randomized participants who received at least one dose of study treatment.

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 Investigator may publish results for his/her study site after publication of results of entire multicenter trial, or after public disclosure of the results online if a multicenter manuscript is not planned. Sponsor must be able to review all proposed results communications regarding study 60 days prior to submission for publication/presentation. Information identified by the Sponsor as confidential must be deleted prior to submission.
Publication restrictions are in place

Restriction type: OTHER