Efficacy and safety of sitagliptin added to ongoing metformin and pioglitazone combination therapy in a randomized, placebo-controlled, 26-week trial in patients with type 2 diabetes

Aims: To assess efficacy and safety of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in combination therapy with metformin (>= 1500 mg/day) and pioglitazone (>= 30 mg/day) in patients with type 2 diabetes (T2DM) with inadequate glycemic control (hemoglobin A(1c) [HbA(1c)] >= 7.5% and <= 11%). Methods: This placebo-controlled, double-blind study included 313 patients, mean baseline HbA(1c) = 8.7%, who were randomized to receive sitagliptin 100 mg/day or placebo for 26 weeks. Results: The addition of sitagliptin led to significant (P<.001) mean changes from baseline relative to placebo in HbA(1c) (-0.7%), fasting plasma glucose (-1.0 mmol/L), and 2-h post-meal glucose (-2.2 mmol/L). In patients with baseline HbA(1c) mean changes from baseline in HbA(1c) were -1.6% and -0.8% for the sitagliptin and placebo groups, respectively (between-group difference -0.8%; P<.001). The incidences of reported adverse events were generally similar between the treatment groups. Incidences of symptomatic hypoglycemia were 7/157 [4.5%] and 6/156 [3.8%] in the sitagliptin and placebo groups, respectively (P = .786). Two patients, both in the placebo group, experienced an episode of hypoglycemia that required non-medical assistance. Conclusions: In this 26-week study, addition of sitagliptin to combination therapy with metformin and pioglitazone improved glycemic control and was generally well tolerated. (C) 2013 Elsevier Inc. All rights reserved.