Effect Of Initial Combination Therapy With Sitagliptin, A Dipeptidyl Peptidase-4 Inhibitor, And Pioglitazone On Glycemic Control And Measures Of Beta-Cell Function In Patients With Type 2 Diabetes

P>Aim/hypothesis:To assess the safety and efficacy of initial combination therapy with sitagliptin and pioglitazone compared with pioglitazone monotherapy in drug-naive patients with type 2 diabetes.Methods: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.Results: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 beta-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).Conclusion/interpretation:Initial combination therapy with sitagliptin and pioglitazone substantially improved glycemic control and was generally well-tolerated compared with pioglitazone monotherapy.