A randomized clinical trial of the safety and efficacy of sitagliptin in patients with type 2 diabetes mellitus inadequately controlled by acarbose alone

Abstract

Objective: To evaluate the safety and efficacy of sitagliptin when added to the treatment of patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on acarbose monotherapy.

Research design and methods: This was a multicenter, randomized, placebo-controlled, double-blind clinical trial. Patients (N = 381) with T2DM and inadequate glycemic control (glycated hemoglobin [HbA1c] ≥ 7.0% and ≤10.0%) on acarbose monotherapy (at least 50 mg three times daily) were randomized in a 1:1 ratio to receive the addition of sitagliptin 100 mg or matching placebo once daily for 24 weeks.

Main outcome measures: Changes from baseline in HbA1c and fasting plasma glucose (FPG) at Week 24.

Results: The mean baseline HbA1c in randomized patients was 8.1%. At Week 24, the placebo-controlled, least squares mean changes from baseline (95% confidence interval) in HbA1c and FPG in the sitagliptin group were −0.62% and −0.8 mmol/L (p < .001), respectively. At Week 24, 37.8% of patients in the sitagliptin group were at HbA1c goal of <7% compared with 17.2% in the placebo group (p < .001). Sitagliptin was generally well tolerated, and there were no significant between-group differences in prespecified safety parameters (symptomatic hypoglycemia, diarrhea, abdominal pain, nausea, vomiting). A higher incidence of serious adverse events was observed in the sitagliptin group (5.2%) relative to placebo (0.5%); all but one, in the sitagliptin group, were not considered related to drug.

Conclusions: Sitagliptin was generally well tolerated and provided statistically superior and clinically meaningful improvements in glycemic control after 24 weeks of treatment compared to placebo when added to treatment of patients with inadequate glycemic control on acarbose monotherapy.

Clinicaltrials.gov: NCT01177384.

Keywords:

• Acarbose
• DPP-4 inhibitor
• incretin therapy
• sitagliptin

Transparency

Declaration of funding

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

Author contributions: W.W., G.N., J.M., X.L., S.Z., F.W., L.X., E.A.O’N., K.P.F., S.S.E., K.D.K., and R.R.S. are responsible for the work described in this paper. All authors were involved in at least one of the following: conception, design, acquisition, analysis, statistical analysis, and interpretation of data in addition to drafting the manuscript and/or revising/reviewing the manuscript for important intellectual content. All authors provided final approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Declaration of financial/other relationships

F.W., L.X., E.A.O’N., K.P.F., S.S.E., K.D.K., and R.R.S. have disclosed that they are or were employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and may own stock and/or hold stock options in the company. W.W., G.N., J.M., X.L., and S.Z. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewer 1 has given talks and attended conferences for numerous pharmaceutical companies including MSD. Peer reviewer 2 has 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, USA.