A randomized, placebo‐ and sitagliptin‐controlled trial of the safety and efficacy of omarigliptin, a once‐weekly dipeptidyl peptidase‐4 inhibitor, in Japanese patients with type 2 diabetes

Abstract

AimsTo assess the safety and efficacy of omarigliptin in Japanese patients with type 2 diabetes (T2D).MethodsIn a 24‐week double‐blind trial, 414 patients with T2D were randomized to omarigliptin 25 mg once weekly, sitagliptin 50 mg once daily or placebo. The double‐blind period was followed by a 28‐week open‐label extension during which all patients received omarigliptin 25 mg once weekly. Efficacy endpoints were glycated haemoglobin (HbA1c), 2‐hour postprandial glucose (PPG) and fasting plasma glucose (FPG) levels.ResultsAfter 24 weeks, the least squares (LS) mean change from baseline in HbA1c was −0.66% for omarigliptin, −0.65% for sitagliptin and 0.13% for placebo. The difference in LS mean for omarigliptin vs placebo was −0.80% (P < .001). The difference in LS mean for omarigliptin vs sitagliptin was −0.02% (95% confidence interval −0.15, 0.12), which met the criterion for non‐inferiority to sitagliptin. Both active treatments provided significant reductions in FPG and 2‐hour PPG compared with placebo (P < .001). Over the 24‐week double‐blind period, there were no clinically meaningful differences in the incidence rates of adverse events among the treatment groups. There was 1 episode of symptomatic hypoglycaemia in the sitagliptin group and none in the omarigliptin or placebo groups. In the 28‐week open‐label period, omarigliptin provided persistent improvements in glycaemic control without notable change in safety profile compared with the double‐blind period. Omarigliptin had no meaningful effect on body weight.ConclusionsIn Japanese patients with T2D, omarigliptin 25 mg once weekly provided significant glucose‐lowering compared with placebo and was non‐inferior to sitagliptin 50 mg once daily. Omarigliptin was generally well tolerated for up to 52 weeks.

Risk of any hypoglycaemia with newer antihyperglycaemic agents in patients with type 2 diabetes: A systematic review and meta‐analysis

“…Of the 22 089 hits retrieved from our search, 144 studies met our inclusion criteria (Figure ). An agreement value ( κ ) of 80% was achieved for studies requiring detailed analysis and extraction.…”

“…An agreement value ( κ ) of 80% was achieved for studies requiring detailed analysis and extraction. Fourteen of these studies contained multiple intervention arms suitable for inclusion in more than 1 comparison (five studies were included in three comparisons and nine studies in two comparisons). Only 1 of the 14 studies included a separate placebo arm for each intervention being evaluated .…”

“…Only 1 of the 14 studies included a separate placebo arm for each intervention being evaluated . In 3 of the 14 multi‐intervention studies, the 2 AHA being evaluated were within the same class and thus pooled estimate, necessitating the need for the “shared” placebo to be split . Thus, in total, 163 studies (n = 53 713) were pooled for 10 comparisons; 9 studies (n = 2630 participants) in metformin monotherapy, 47 studies (n = 14 926) in DPP4i monotherapy, 11 studies in GLP1RA monotherapy (n = 2705), 19 studies in SGLT2i monotherapy (6647), 29 studies in DPP4i added to metformin (n = 9679), 11 studies in GLP1RA added to metformin (n = 4096), 18 studies in SGLT2i added to metformin (n = 7201), 5 studies in second AHA added to nonmetformin background (n = 953), 6 studies in dual therapy initiation (n = 2215) and 8 studies in triple therapy (n = 2661).…”

A randomized, placebo-controlled study of the cardiovascular safety of the once-weekly DPP-4 inhibitor omarigliptin in patients with type 2 diabetes mellitus

“…Omarigliptin is an oral dipeptidyl peptidase-4 (DPP-4) inhibitor for the treatment of type 2 diabetes mellitus (T2DM) with a half-life that allows once-weekly dosing [ 1 ]. Omarigliptin has previously been demonstrated to have efficacy comparable to that of the daily DPP-4 inhibitor sitagliptin [ 2 , 3 ]. Omarigliptin has been marketed in Japan (as MARIZEV™) for the treatment of patients with T2DM since 2015.…”

Efficacy and Patient Satisfaction of Dipeptidyl Peptidase-4 Inhibitor After Switching From Once-Daily DPP-4 Inhibitor to Once-Weekly Regimen

“…In clinical trials during drug development, trelagliptin was compared to alogliptin and omarigliptin was compared to sitagliptin. Non-inferiority in efficacy and safety was demonstrated for both drugs compared to the existing daily medications [ 2 , 3 ]. It was also recently reported in a meta-analysis that the efficacy and safety of once-weekly medication are comparable to that of existing daily medications [ 4 ].…”