Efficacy and safety of initial combination therapy with sitagliptin and pioglitazone in patients with type 2 diabetes: a 54-week study
Diabetes, Obesity and Metabolism, 07/06/2012
Yoon KH et al. – In this study, initial combination therapy with sitagliptin 100 mg and pioglitazone 30 mg increased to 45 mg after 24 weeks led to a substantial and durable incremental improvement in glycaemic control compared with initial treatment with pioglitazone monotherapy during a 54–week treatment period. Both initial combination therapy with sitagliptin and pioglitazone and pioglitazone monotherapy were generally well tolerated.Methods
- Following a 24-week, randomized, double-blind, parallel-group study.
- Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and pioglitazone on glycaemic control and measures of beta-cell function in patients with type 2 diabetes.
- Int J Clin Pract 2011; 65: 154-164) in which patients were treated with the combination of sitagliptin 100 mg/day and pioglitazone 30 mg/day or monotherapy with pioglitazone 30 mg/day, patients entered a 30-week extension study.
- In the extension study, the pioglitazone dose was increased from 30 to 45 mg/day in both groups.
- Depending upon treatment allocation, patients took one tablet of sitagliptin 100 mg or matching placebo daily.
- Pioglitazone was administered in an open-label fashion as a single 45-mg tablet taken once daily.
- Patients not meeting specific glycaemic goals in the extension study were rescued with metformin therapy.
- Efficacy and safety results for the extension study excluded data after initiation of rescue therapy.
- Of the 520 patients initially randomized, 446 completed the base study and, of these, 317 entered the extension.
- In this extension study cohort, the mean reductions from baseline in HbA1c and fasting plasma glucose (FPG) at the end of the base study (week 24) were -2.5% and -62.1 mg/dl with the combination of sitagliptin 100 mg and pioglitazone 30 mg versus -1.9% and -48.7 mg/dl with pioglitazone monotherapy.
- At the end of the extension study (week 54), the mean reduction in haemoglobin A1c (HbA1c) was -2.4% with the combination of sitagliptin 100 mg and pioglitazone 45 mg versus -1.9% with pioglitazone monotherapy [between-group difference (95% CI) = -0.5% (-0.8, -0.3)] and the mean reduction in FPG was -61.3 mg/dl versus -52.8 mg/dl, respectively [between-group difference (95% CI) = -8.5 mg/dl (-16.3, -0.7)].
- Safety and tolerability of initial treatment with the combination of sitagliptin and pioglitazone and pioglitazone monotherapy were similar.
- As expected, increases in body weight from baseline were observed in both treatment groups at week 54: 4.8 and 4.1 kg in the combination and monotherapy groups, respectively [between-group difference (95% CI) = 0.7 kg (-0.7, 2.1)].