NCT01189890

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

Completed Phase 3 Results posted Last updated 5 June 2017

What this trial tests

Phase 3 trial testing sitagliptin phosphate in Type 2 Diabetes Mellitus in 480 participants. Completed in 31 October 2012.

Timeline

16 August 2010

Primary endpoint
31 October 2012

31 October 2012

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	480
Start date	16 August 2010
Primary completion	31 October 2012
Estimated completion	31 October 2012

Drugs / interventions tested

• sitagliptin phosphate — full drug profile →
• Glimepiride (GLIMEPIRIDE) — full drug profile →
• Placebo to Sitagliptin — full drug profile →
• Placebo to Glimepiride — full drug profile →

Conditions studied

• Type 2 Diabetes Mellitus — all drugs for Type 2 Diabetes Mellitus →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 65 to 85, any sex, with Type 2 Diabetes Mellitus. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Least Squares (LS) Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 30 Primary · Baseline and Week 30

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.

Group	Value	95% CI
Sitagliptin	-0.32	-0.51 – -0.14
Glimepiride	-0.51	-0.69 – -0.33

Number of Participants With an Adverse Event of Symptomatic Hypoglycemia Up to Week 30 Primary · Up to Week 30

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.

Group	Value	95% CI
Sitagliptin	2
Glimepiride	11

Number of Participants Experiencing An Adverse Event (AE) Primary · Up to Week 30

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.

Group	Value	95% CI
Sitagliptin	118
Glimepiride	115

Number of Participants Discontinuing Study Treatment Due to An AE Primary · Up to Week 30

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.

Group	Value	95% CI
Sitagliptin	3
Glimepiride	4

LS Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30 Secondary · Baseline and Week 30

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.

Group	Value	95% CI
Sitagliptin	-14.5	-21.6 – -7.4
Glimepiride	-21.2	-28.3 – -14.0

Percentage of Participants With HbA1c <7.0% at Week 30 Secondary · Week 30

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.

Group	Value	95% CI
Sitagliptin	33.5
Glimepiride	46.6

Percentage of Participants With HbA1c <6.5% at Week 30 Secondary · 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.

Group	Value	95% CI
Sitagliptin	9.1
Glimepiride	20.9

LS Mean Change From Baseline in Participant Body Weight at Week 30 Secondary · Baseline and 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.

Group	Value	95% CI
Sitagliptin	0.4	-0.2 – 1.0
Glimepiride	1.1	0.5 – 1.7

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to Week 32.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Sitagliptin

Serious: 7/241 (3%)

Deaths: —

Glimepiride

Serious: 6/236 (3%)

Deaths: —

Serious adverse events (14 terms)

Reaction	System	Sitagliptin	Glimepiride
Anaemia	Blood and lymphatic system disorders	—	—
Angina Unstable	Cardiac disorders	—	—
Atrial Fibrillation	Cardiac disorders	—	—
Cardiac Failure Chronic	Cardiac disorders	—	—
Gastrointestinal Haemorrhage	Gastrointestinal disorders	—	—
Inguinal Hernia	Gastrointestinal disorders	—	—
Lower Gastrointestinal Haemorrhage	Gastrointestinal disorders	—	—
Gastroenteritis	Infections and infestations	—	—
Colon Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Malignant Melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Prostate Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Nerve Compression	Nervous system disorders	—	—
Syncope	Nervous system disorders	—	—
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	—	—

Other adverse events (3 terms — click to expand)

Reaction	System	Sitagliptin	Glimepiride
Nasopharyngitis	Infections and infestations	—	—
Hypoglycaemia	Metabolism and nutrition disorders	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—

Most-reported serious reactions: Anaemia, Angina Unstable, Atrial Fibrillation, Cardiac Failure Chronic, Gastrointestinal Haemorrhage, Inguinal Hernia, Lower Gastrointestinal Haemorrhage, Gastroenteritis.

Data from ClinicalTrials.gov NCT01189890 adverse events section.

Sponsor's own description

The primary objectives of this study are to determine if sitagliptin treatment is not inferior to that of glimepiride as measured by the change in baseline hemoglobin A1C (HbA1C) after 30 weeks of treatment, and if sitagliptin treatment results in a lower incidence of symptomatic hypoglycemia compared to that of glimepiride. The study will also evaluate if sitagliptin treatment, compared to glimepiride results in improvements in fasting plasma glucose (FPG) levels, and plasma lipid levels after 30 weeks of treatment. Participants will be randomized to either sitagliptin or glimepiride treatment after eligibility for study participation is determined during screening and washout study phases. Participants and study staff will not know to which treatment group they have been randomized (double-blind design). The duration of study participation will be up to 40 weeks (with 9 clinic visits). This will include a screening phase (Visit 1 to Visit 2) of 2 weeks maximum; a 6-week (Visits 2 to 3) oral antihyperglycemic agent (AHA) wash-out phase (for those who have been taking a AHA prior to the study); a placebo run-in phase (Visits 3 to 4), followed by up to 30 weeks of treatment with study medication.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies.
   Li L, Li S, Deng K, Liu J, et al · · 2016 · cited 157× · PMID 26888822 · DOI 10.1136/bmj.i610
2. Translating evidence into practice: eligibility criteria fail to eliminate clinically significant differences between real-world and study populations.
   Averitt AJ, Weng C, Ryan P, Perotte A. · · 2020 · cited 98× · PMID 32411828 · DOI 10.1038/s41746-020-0277-8
3. Dipeptidyl peptidase-4 inhibitors and cancer risk in patients with type 2 diabetes: a meta-analysis of randomized clinical trials.
   Zhao M, Chen J, Yuan Y, Zou Z, et al · · 2017 · cited 50× · PMID 28811622 · DOI 10.1038/s41598-017-07921-2
4. Efficacy and Tolerability of Sitagliptin Compared with Glimepiride in Elderly Patients with Type 2 Diabetes Mellitus and Inadequate Glycemic Control: A Randomized, Double-Blind, Non-Inferiority Trial.
   Hartley P, Shentu Y, Betz-Schiff P, Golm GT, et al · · 2015 · cited 24× · PMID 26041585 · DOI 10.1007/s40266-015-0271-z
5. The dipeptidyl peptidase (DPP)-4 inhibitors for type 2 diabetes mellitus in challenging patient groups.
   Kountz D. · · 2013 · cited 8× · PMID 24287690 · DOI 10.1007/s12325-013-0071-y