A randomized, double-blind, non-inferiority trial evaluating the efficacy and safety of omarigliptin, a once-weekly DPP-4 inhibitor, or glimepiride in patients with type 2 diabetes inadequately controlled on metformin monotherapy

Abstract

Objective: To evaluate the efficacy and safety of adding the once-weekly DPP-4 inhibitor omarigliptin or the sulfonylurea glimepiride to the treatment regimen of patients with type 2 diabetes (T2DM) and inadequate glycemic control on metformin monotherapy.

Methods: Patients with T2DM and HbA1c ≥6.5% to ≤9.0% while on a stable dose of metformin (≥1500 mg/day) were randomized to omarigliptin 25 mg once-weekly (n = 376) or glimepiride up to 6 mg once daily (n = 375) for 54 weeks. The primary hypothesis was that omarigliptin is non-inferior to glimepiride in reducing HbA1c at week 54.

Results: The mean baseline HbA1c was 7.5% in the omarigliptin group and 7.4% in the glimepiride group. After 54 weeks, the least squares (LS) mean change from baseline in HbA1c was –0.30% in the omarigliptin group and –0.48% in the glimepiride group, with a between-group difference (95% CI) of 0.18% (0.06, 0.30), which met the pre-specified criterion for declaring non-inferiority. The incidence of symptomatic hypoglycemia was 5.3% in the omarigliptin group and 26.7% in the glimepiride group. With the exception of hypoglycemia, the incidences of adverse events and discontinuations were similar between treatment groups. Relative to baseline, omarigliptin was associated with a mean weight loss (−0.4 kg) and glimepiride a mean weight gain (+1.5 kg).

Conclusions: After 54 weeks, as add-on therapy to metformin, once-weekly omarigliptin was generally well tolerated and non-inferior to glimepiride in improving glycemic control, with a lower incidence of hypoglycemia and with weight loss vs weight gain.

Keywords:

• MK-3102
• incretin therapy
• oral antihyperglycemic agent
• sulfonylurea

Transparency

Declaration of funding

Merck & Co., Inc., Kenilworth, NJ, USA, provided financial support for the conduct of the study.

Declaration of financial/other relationships

YH has received research grants, consultant & speaker honoraria from Amarin, Amgen, AZ, BMS, BI, BI-Lilly, Eisai, Intarcia, Janssen, Lexicon, Lilly, Merck Pfizer, Novo Nordisk, Regeneron, and Sanofi. BL, IG, CI, EAO’N, ZW, SS, KDK, SSE, and EL are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, who may own stock and/or hold stock options in the Company. CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

Editorial assistance was provided by Jennifer Rotonda, PhD, and Michele McColgan, BA, of Merck & Co., Inc., Kenilworth, NJ. Trial registration numbers: Clinical Trials.gov: NCT01682759, EudraCT Number: 2012-002309-23.