Omarigliptin monotherapy improved glycemic control for people with type 2 diabetes (T2D) over a 54-week trial period and was generally well tolerated with a low risk of hypoglycemia, according to a study accepted for publication in Diabetes Research and Clinical Practice.
Omarigliptin (MK-3102) is an investigational, site-selective, oral dipeptidyl peptidase-4 (DPP-4) inhibitor with a half-life that permits dosing once a week. The researchers aimed to assess the efficacy, safety, and tolerability of the agent compared with placebo when used as monotherapy in patients with T2D. Safety and tolerability also were assessed during treatment and for 21 days once treatment ended.
The multicenter, 10-country trial was a double-blind, randomized, parallel group study of 329 women and men aged ≥18 years. At the study start, the participants were either not taking glucose-lowering medications or taken off monotherapy or low-dose dual therapy and randomly assigned in study phase A to omarigliptin 25 mg/wk (165 participants) or placebo (n=164) for 24 weeks. Phase B was a 30-week active-controlled, double-blind treatment period during which the continuing efficacy and safety of omarigliptin were assessed compared with placebo to which metformin was added.
At the start of the study, the mean baseline glycated hemoglobin (HbA1c) was 8.0% for the omarigliptin group and 8.1% for the placebo group. The least squares mean change from baseline at week 24, the primary end point, was -0.49% (95% CI, -0.73 to -0.24) in the omarigliptin group and -0.10% (95% CI, -0.34 to 0.14) in the placebo group. The difference between the two groups was -0.39% (95% CI, -0.59 to -0.19; P <.001).
Other oral glucose-lowering drugs were prohibited during the study except as rescue therapy. Participants requiring such treatment were given open-label metformin prior to week 24. After that time they were given open-label glimepiride as rescue therapy.
By the primary and secondary end points, weeks 24 and 54 respectively, the incidence of adverse events for omarigliptin was similar to that for the placebo group. By 54 weeks, there had been no reported cases of symptomatic hypoglycemia in the omarigliptin group and 4 cases in the placebo group. One case of asymptomatic hypoglycemia was reported in the omarigliptin group; in the placebo group, one person had asthma-bronchospasm. During the course of the study, a majority of the omarigliptin group experienced a persistent reduction in HbA1c.
Phase B was a 30-week extension period during which time those who received omarigliptin continued on it and those who received placebo were given metformin 500 mg twice daily, which was titrated up to 1000 mg – if they had not received that medication as rescue therapy during phase A. Those who had received metformin as rescue therapy were continued on that medication through phase B of the trial.
The researchers note that there was no clinically relevant increase in body weight in the omarigliptin group. In addition, the investigators found that prohibited metformin was used by twice as many patients in the placebo group as in the omarigliptin group; therefore, efficacy of omarigliptin may be more pronounced than it appeared in this study.
Philip Home reports receiving grants and/or personal fees from Merck, AstraZeneca, Hanmi, GlaxoSmithKline, Novo Nordisk, Sanofi, Biocon, and Janssen. R. Ravi Shankar, Ira Gantz, Carol Iredale, Edward A. O’Neill, Lokesh Jain, Annpey Pong, Shailaja Suryawanshi, Samuel S. Engel, Keith D. Kaufman, and Eseng Lai are employees at Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc.
Funding for the study was provided by Merck Sharp & Dohme Corp, a subsidiary of Merck & Dohme Co.
Home P, Ravi Shankar R, Gantz I, et al. A randomized, double-blind trial evaluating the efficacy and safety of monotherapy with the once-weekly dipeptidyl peptidase-4 inhibitor omarigliptin in people with type 2 diabetes [published online October 24, 2017]. Diabetes Res Clin Pract. doi: 10.1016/j.diabres.2017.10.018