Saxagliptin as initial therapy in treatment-naive Indian adults with type 2 diabetes mellitus inadequately controlled with diet and exercise alone: a randomized, double-blind, placebo-controlled, phase IIIb clinical study

Abstract

The prevalence of type 2 diabetes mellitus (T2DM) is rapidly increasing in India. Additional antihyperglycemic treatment options are important for patients who cannot achieve glycemic control through diet and exercise. The dipeptidyl peptidase 4 (DPP-4) inhibitor saxagliptin is efficacious and well tolerated in Western patients with T2DM but has not been tested prospectively in a dedicated study in Indian patients. A multicenter, randomized, double-blind, placebo-controlled, parallel-group study was conducted in India to evaluate the efficacy and safety of saxagliptin. Treatment-naive adults with T2DM and glycated hemoglobin (HbA_1c) between 7.0 % and 10.0 % at randomization were recruited. Patients were assigned 1:1 to receive saxagliptin 5 mg or matching placebo tablets once daily for 24 weeks. The primary efficacy endpoint was change from baseline to week 24 in HbA_1c, using last observation carried forward methodology. Two hundred thirteen patients were randomized (saxagliptin, N = 107; placebo, N = 106). Adjusted mean absolute reductions in HbA_1c from baseline to week 24 were significantly greater with saxagliptin (−0.51 % ;N = 104) versus placebo (−0.05 %; n = 105; difference for saxagliptin vs placebo, −0.46 %; SE, 0.14 %; 95 % CI, −0.73 %, −0.18 %; P = 0.0011). The incidence of adverse events was 47.7 % with saxagliptin and 45.3 % with placebo. No deaths, serious adverse events, or reported or confirmed hypoglycemic events occurred. Saxagliptin provided statistically and clinically significant improvement in HbA_1c for Indian patients, similar to previous findings in Western study populations. Saxagliptin was well tolerated, with no previously unidentified safety findings, and had a safety profile comparable to placebo.