Clinical trial NCT01189890: Safety and Efficacy of Sitagliptin Compared With Glimepiride in Elderly Participants With Type 2 Diabetes Mellitus (MK-0431-251)
Official title: A Phase III, Multicenter, Double-Blind, Randomized, Active-Controlled Study to Evaluate the Safety and Efficacy of Sitagliptin Compared With Glimepiride in Elderly Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Keywords: Type 2 Diabetes Mellitus, Hemoglobin A1C, glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), dipeptidyl peptidase 4 inhibitor (DPP-4)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2010-08-27
Enrollment: 480
Sex: ALL
Minimum age (years): 65
Maximum age (years): 85
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: The dose of sitagliptin will be 100 mg once daily (QD) or 50 mg QD based on the participant's estimated glomerular filtration rate (eGFR). The starting dose of glimepiride (1 mg QD) may be up-titrated as needed to optimize glycemic control over the first 18 weeks to a maximum dose of 6 mg/day, after which the dose will not be increased for the rest of the study (down-titration to avoid or control hypoglycemia is allowed).

Eligibility criteria: Inclusion Criteria

* Diagnosis of type 2 diabetes mellitus

Exclusion Criteria

* History of type 1 diabetes mellitus
* Has undergone a surgical procedure within the prior 4 weeks.
* Current participation in, or has participated, in another study with an investigational device or compound, with the prior 12 weeks, and/or is not willing to refrain from participating in any other study while participating in this study
* Hypersensitivity or contraindication to any sulfonylurea (e.g., glimepiride) medication
* Has been on an investigational or approved dipeptidyl peptidase-4 (DPP-4) inhibitor agent (e.g., sitagliptin, saxagliptin)
* Presence of human immunodeficiency virus (HIV)
* Current participation in a weight loss program or is receiving weight loss medication
* History of blood disorder, certain cancers, heart, liver or kidney disease
* Current or past use of recreational or illicit drugs, or a history of drug abuse or dependence, or increased alcohol consumption

Primary outcomes:
measure: Least Squares (LS) Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 30
timeFrame: Baseline and Week 30
measure: Number of Participants With an Adverse Event of Symptomatic Hypoglycemia Up to Week 30
timeFrame: Up to Week 30
measure: Number of Participants Experiencing An Adverse Event (AE)
timeFrame: Up to Week 30
measure: Number of Participants Discontinuing Study Treatment Due to An AE
timeFrame: Up to Week 30
Secondary outcomes:
measure: LS Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30
timeFrame: Baseline and Week 30
measure: Percentage of Participants With HbA1c <7.0% at Week 30
timeFrame: Week 30
measure: Percentage of Participants With HbA1c <6.5% at Week 30
timeFrame: Week 30
measure: LS Mean Change From Baseline in Participant Body Weight at Week 30
timeFrame: Baseline and Week 30
Other outcomes:
Locations:
Study officials:
References:
citation: Hartley P, Shentu Y, Betz-Schiff P, Golm GT, Sisk CM, Engel SS, Shankar RR. 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. Drugs Aging. 2015 Jun;32(6):469-76. doi: 10.1007/s40266-015-0271-z.