Efficacy and Safety of a Fixed-Dose Combination of Vildagliptin and Pioglitazone in Indian Patients With Type 2 Diabetes Mellitus: A Randomized, Open-Label, Comparative, Phase III Study.

ABSTRACT

Background Type 2 diabetes mellitus (T2DM) arises due to a range of pathological abnormalities, necessitating a combination therapy to achieve optimal glycemic control. Vildagliptin, an effective and selective DPP-4 inhibitor, and pioglitazone, an insulin sensitizer, offer distinct mechanisms of action. Hence, the integration of these medications represents a logical and justified therapeutic strategy Objective To compare the efficacy, safety, and tolerability of vildagliptin and pioglitazone 50 mg/15 mg fixed-dose combination (FDC) tablets with individual monotherapy vildagliptin 50 mg and pioglitazone 15 mg tablets in Indian T2DM patients who were inadequately controlled on metformin monotherapy. Methods This was a randomized, open-label, comparative, multicenter, phase III study involving 195 T2DM patients with inadequate glycemic control on metformin ≥ 1000 mg/day. Patients were randomly assigned in a 111 ratio to the test product group (n=65) (vildagliptin 50 mg + pioglitazone 15 mg FDC tablets), reference product group 1 (n=65) (vildagliptin 50 mg tablet), or reference product group 2 (n=65) (pioglitazone 15 mg tablet reference product). The primary endpoint was the mean change in HbA1c levels from baseline to end of the study visit (12 weeks (84 days ±2)). The secondary endpoints were the mean change in fasting plasma glucose (FPG) and 2-hr postprandial plasma glucose (2-hr PPG) levels. Safety parameters were assessed till the end of the study. Results A total of 178 patients completed the study. At 12 weeks, the mean HbA1c level in the test group reduced to 6.85 ± 1.27%, in the reference product 1 group to 7.56 ± 1.72%, and in the reference product 2 groups to 7.37 ± 1.59%. The mean change in Hb1Ac from baseline in the test group was statistically significant compared to the reference groups (p=0.037). Similarly, the mean changes in the FPG and 2hr-PPG with the test product were statistically significant compared to reference products (p=0.041). The adverse events were comparable across all the treatment groups. Conclusion In Indian T2DM patients inadequately controlled on a daily maximum dose of metformin, treatment with vildagliptin and pioglitazone FDC showed better glycemic control than either vildagliptin or pioglitazone along with a good tolerability profile.