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Efficacy and safety of initial combination treatment with sitagliptin and pioglitazone—a factorial study
Author(s) -
Henry R. R.,
Staels B.,
Fonseca V. A.,
Chou M. Z.,
Teng R.,
Golm G. T.,
Langdon R. B.,
Kaufman K. D.,
Steinberg H.,
Goldstein B. J.
Publication year - 2014
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12194
Subject(s) - pioglitazone , sitagliptin , medicine , combination therapy , type 2 diabetes , clinical endpoint , urology , pharmacology , adverse effect , diabetes mellitus , randomized controlled trial , endocrinology
Aim To evaluate the efficacy and safety of initial combination therapy of sitagliptin 100 mg/day coadministered with all marketed doses of pioglitazone in patients with type 2 diabetes. Methods Patients with A1c ≥7.5 and ≤11.0% were randomized among seven arms that received, once daily, 100 mg sitagliptin alone; 15, 30 or 45 mg pioglitazone alone, or 100 mg sitagliptin plus 15, 30 or 45 mg pioglitazone for 54 weeks. The primary endpoint was change from baseline in A1c at week 24. Protocol‐specified analyses compared combination therapies with monotherapies at respective dose‐strengths and combination of sitagliptin plus pioglitazone 30 mg with pioglitazone 45 mg monotherapy. Post‐hoc analyses compared sitagliptin plus pioglitazone 15 mg with pioglitazone monotherapy at the two higher doses. Results Initial combination therapy with sitagliptin and pioglitazone provided significantly greater reductions in A1c (0.4–0.7% differences) and other glycaemic endpoints than either monotherapy at the same doses. Combining sitagliptin with low‐dose pioglitazone generally produced greater glycaemic improvements than higher doses of pioglitazone monotherapy (0.3–0.4% differences in A1c ). Combination therapy was generally well tolerated; adverse events ( AEs ) of hypoglycaemia were reported with similar incidence (7.8–11.1%) in all treatment groups over the 54 weeks of study; oedema was reported in 0.5% of patients in the sitagliptin monotherapy group and 2.7–5.3% among pioglitazone‐treated groups. Significant weight gain was observed in all combination‐treated groups compared with the sitagliptin monotherapy group. Conclusions Initial combination therapy with sitagliptin and pioglitazone provided better glycaemic control than either monotherapy and was generally well tolerated.