Dataset Information

A Randomized, Placebo-Controlled Trial Evaluating the Safety and Efficacy of Adding Omarigliptin to Antihyperglycemic Therapies in Japanese Patients with Type 2 Diabetes and Inadequate Glycemic Control.

ABSTRACT:

Introduction

Daily dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used with other orally administered antihyperglycemic agents (AHA), as combination therapy, to treat Japanese patients with type 2 diabetes. When combination therapy is indicated, use of a once-weekly (q.w.) orally administered DPP-4 inhibitor might be an appropriate therapeutic option for some patients.

Methods

A 52-week trial was conducted to assess the safety and tolerability (primary objectives) and glycemic efficacy (secondary objectives) of the q.w. DPP-4 inhibitor omarigliptin as add-on therapy to five different classes of orally administered AHA [sulfonylurea (SU), glinide (GL), biguanide (BG), thiazolidinedione (TZD), or α-glucosidase inhibitor (AGI)] commonly used in Japan and having different mechanisms of drug action from DPP-4 inhibitors. The trial consisted of an initial 24-week double-blind, placebo-controlled period during which patients (stratified by background AHA) were randomized to omarigliptin 25 mg q.w. or placebo, followed by a 28-week open-label period during which patients on placebo were switched to omarigliptin.

Results

After 24 weeks, the percentages of patients with adverse events (AEs), serious AEs, drug-related AEs, AEs of symptomatic hypoglycemia, or who discontinued from trial medication because of an AE were generally similar in the omarigliptin and placebo groups, in all background AHA strata and in the overall population. From a mean baseline HbA1c of approximately 8.0%, the placebo-adjusted least-squares mean changes from baseline ranged from -0.80% (AGI stratum) to -1.16% (TZD stratum); p < 0.001 for all background AHA strata. During the open-label period, no safety signals emerged with longer-term treatment. At week 52, the change from baseline in HbA1c in the omarigliptin/omarigliptin group was similar to that of the placebo/omarigliptin group.

Conclusions

Addition of once-weekly omarigliptin to AHA therapy with an SU, GL, BG, TZD, or AGI for up to 52 weeks was generally safe and well tolerated, and provided persistent efficacy.

Clinical trial registration

ClinicalTrials.gov: NCT01697592.

Funding

MSD K.K., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

SUBMITTER: Gantz I

PROVIDER: S-EPMC5544607 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Type 2 diabetes (T2D) is a progressive disease that often requires a patient to use multiple antihyperglycemic agents to achieve glycemic control with disease progression. Omarigliptin is a once-weekly dipeptidyl peptidase-4 inhibitor. The purpose of this trial was to assess the efficacy and safety of adding omarigliptin to the treatment regimen of patients with T2D inadequately controlled by dual therapy with metformin and glimepiride.Patients with T2D and HbA1c ?7.5% and ?10.5% while on metformin (?1500 mg/day) and glimepiride (?4 mg/day) were randomized to omarigliptin 25 mg once-weekly (N = 154) or placebo (N = 153) for 24 weeks. The primary objective was to assess whether omarigliptin was superior to placebo in reducing HbA1c at Week 24. Secondary objectives were to assess the effects of omarigliptin vs. placebo on FPG and the proportion of subjects attaining HbA1c goals of <7% and <6.5%.From a mean baseline HbA1c of 8.5% (omarigliptin) and 8.6% (placebo), the least squares (LS) mean change from baseline in HbA1c at Week 24 was -0.67% in the omarigliptin group and -0.06% in the placebo group, with a between-group difference (95% CI) of -0.61% (-0.85, -0.38). Treatment with omarigliptin resulted in a significantly greater reduction in FPG relative to placebo (LS mean difference [95% CI] -0.9 mmol/L [-1.4, -0.4]; p < 0.001). The proportion of patients achieving glycemic goals of <7.0% and <6.5% was higher in the omarigliptin group relative to the placebo group. The overall incidences of adverse events (AEs), serious AEs, drug-related AEs and discontinuations were generally similar between treatment groups. The incidence of symptomatic hypoglycemia was 10.5% in the omarigliptin group and 8.5% in the placebo group. Relative to baseline, omarigliptin and placebo treatments were associated with LS mean changes in body weight of -0.1 kg and -0.9 kg, respectively.In patients with T2D and inadequate glycemic control on dual therapy with metformin and glimepiride, compared with placebo, once-weekly omarigliptin provided greater improvement in glycemic control and was generally well tolerated.ClinicalTrials.gov: NCT01704261 , EudraCT Number: 2012-002612-10. Trial Registration Date: October 8, 2012.

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