Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and pioglitazone on glycemic control and measures of β-cell function in patients with type 2 diabetes

Abstract

To assess the safety and efficacy of initial combination therapy with sitagliptin and pioglitazone compared with pioglitazone monotherapy in drug-naïve patients with type 2 diabetes. A total of 520 patients were randomised to initial combination therapy with sitagliptin 100 mg q.d. and pioglitazone 30 mg q.d. or pioglitazone 30 mg q.d. monotherapy for 24 weeks. Initial combination therapy with sitagliptin and pioglitazone led to a mean reduction from baseline in A1C of -2.4% compared with -1.5% for pioglitazone monotherapy (p<0.001). Mean reductions from baseline were greater in patients with a baseline A1C≥10% (-3.0% with combination therapy vs. -2.1% with pioglitazone monotherapy) compared with patients with a baseline A1C<10% (-2.0% with combination therapy vs. -1.1% with pioglitazone monotherapy). Sixty percent of patients in the combination therapy group vs. 28% in the pioglitazone monotherapy group had an A1C of <7% at week 24 (p<0.001). Fasting plasma glucose decreased by -63.0 mg/dl (-3.5 mmol/l) in the combination therapy group compared with -40.2 mg/dl (-2.2 mmol/l) for pioglitazone monotherapy (p<0.001), and 2-h post meal glucose decreased by -113.6 mg/dl (-6.3 mmol/l) with combination therapy compared with -68.9 mg/dl (-3.8 mmol/l) for pioglitazone monotherapy (p<0.001). Measures related to β-cell function also improved significantly with combination therapy compared with pioglitazone monotherapy. Combination therapy was generally well-tolerated compared with pioglitazone monotherapy, with similar incidences of hypoglycemia (1.1% and 0.8%, respectively), gastrointestinal adverse events (5.7% and 6.9%, respectively), and oedema (2.7% and 3.5%, respectively). Initial combination therapy with sitagliptin and pioglitazone substantially improved glycemic control and was generally well-tolerated compared with pioglitazone monotherapy.