Once-daily sitagliptin, a dipeptidyl peptidase-4 inhibitor, for the treatment of patients with type 2 diabetes

Abstract

Objective: Sitagliptin, an oral, potent, and selective dipeptidyl peptidase-4 (DPP‑4) inhibitor was evaluated as once-daily monotherapy in a 12-week randomized, double-blind, placebo-controlled, parallel group, dose-ranging study. Additionally, the glycemic response to sitagliptin 100 mg daily was evaluated as a once-daily (100 mg once-daily) or twice-daily (50 mg twice-daily) dosing regimen. Research design and methods: In a multinational, double-blind, randomized, placebo-controlled, parallel-group, dose-range finding study, 555 patients, 23–74 years of age, with HbA_1c of 6.5–10.0% were randomized to one of five treatment groups: placebo, sitagliptin 25, 50 or 100 mg once-daily, or sitagliptin 50 mg twice-daily for 12 weeks. The efficacy analysis was based on the all-patients-treated population using an ANCOVA model. Results: Mean baseline HbA_1c ranged from 7.6 to 7.8% across treatment groups, with 29% of all patients with values ≤ 7%. After 12 weeks, treatment with all doses of sitagliptin significantly ( p < 0.05) reduced HbA_1c by –0.39 to –0.56% and fasting plasma glucose by –11.0 to –17.2 mg/dLrelative to placebo, with the greatest reduction observed in the 100-mg once-daily group. Mean daily glucose was significantly ( p < 0.05) reduced by –14.0 to –22.6 mg/dL with all doses of sitagliptin relative to placebo. HOMA‑β was significantly ( p < 0.05) increased by 11.3–15.2 with all sitagliptin doses relative to placebo. QUICKI and HOMA‑IR were not significantly changed with sitagliptin treatment. There were no significant differences observed between the sitagliptin 100 mg once-daily and 50 mg twice-daily groups for any parameter. For sitagliptin, the incidence of adverse events of hypoglycemia was low, with one event in each of the 25- and 50-mg once-daily and 50-mg twice-daily treatment groups and two events in the 100 mg once-daily treatment group. There was no mean change in body weight with sitagliptin relative to placebo. Study duration may be a limitation because the extent of the glycemic response and the safety and tolerability may not have been fully elucidated in this 12-week study. Conclusion: Sitagliptin monotherapy improved indices of glycemic control compared to placebo and was generally well-tolerated in patients with type 2 diabetes. The glycemic response to treatment with sitagliptin 100 mg/day was similar between the sitagliptin 100-mg once-daily and 50-mg twice-daily dose regimens.