A randomised, double-blind, trial of the safety and efficacy of omarigliptin (a once-weekly DPP-4 inhibitor) in subjects with type 2 diabetes and renal impairment

Abstract

Aims: To assess the safety and efficacy of omarigliptin in subjects with type 2 diabetes mellitus (T2DM) and chronic renal impairment (RI).

Methods: Patients with T2DM with moderate RI (estimated glomerular filtration rate [eGFR] ≥30 to <60 mL/min/1.73 m2 ) (N=114), severe RI (eGFR <30 mL/min/1.73 m2 ) (N=55) or end-stage renal disease on dialysis (N=44), who were either not on an antihyperglycaemic agent therapy for at least 12 weeks at screening, washed-off of oral antihyperglycaemic agent monotherapy or low-dose dual combination therapy, or on insulin monotherapy, with baseline glycated haemoglobin (HbA1c) of 6.5%-10.0% were randomised to omarigliptin or to placebo for 24 weeks (primary end-point) followed by a 30-week period with subjects on placebo switched to blinded glipizide (if not on insulin).

Results: After 24 weeks, from a mean baseline HbA1c of 8.4% in the omarigliptin group and 8.3% in the placebo group, the least squares mean (95% CI) change from baseline in HbA1c in the overall population (all renal strata combined) was -0.77% (-1.00 to -0.54) in the omarigliptin group and -0.44% (-0.67 to -0.21) in the placebo group; between-group difference of -0.33% (-0.63 to -0.02); P=0.035. After 24 weeks, the incidences of subjects with symptomatic hypoglycaemia, one or more adverse event (AE), drug-related AE, serious AE and discontinuation due to an AE were similar in the omarigliptin and placebo groups.

Conclusions: In this study in subjects with T2DM and RI, relative to placebo, omarigliptin provided clinically meaningful reductions in HbA1c, had a similar incidence of symptomatic hypoglycaemia and was generally well tolerated.

Conflict of interest statement

Ira Gantz, Geraldine Mendizabal, Lucila Durlach, Edward A. O'Neill, Zachary Zimmer, Shailaja Suryawanshi, Samuel S. Engel and Eseng Lai are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, who may own stock and/or hold stock options in the Company. Antonio Chacra lists no conflict of interest.

© 2017 The Authors. International Journal of Clinical Practice Published by John Wiley & Sons Ltd.

Figures

Figure 1

Efficacy measures through Week 54; A) change from baseline HbA1c (%); B) change from baseline fasting plasma glucose (mmol/L); • omarigliptin; ° placebo; based on a model with terms for treatment, chronic renal impairment (RI) stratum, baseline treatment with insulin stratum, time, the interaction of time by treatment, the interaction of time by RI stratum, and the interaction of time by baseline treatment with insulin stratum with the restriction of a common baseline mean across treatment groups