Efficacy and Safety of Fixed-dose Combination of Teneligliptin and Pioglitazone versus Respective Monotherapies in Patients with Type 2 Diabetes Mellitus Inadequately Controlled on Metformin: A Phase III Randomized Parallel Group Study

Abstract

Background and aims: Teneligliptin, a third generation DPP-4 inhibitor, decreases the degradation of incretins, while Pioglitazone, a potent insulin sensitizer, reduces the glucose output from liver. A combination of these two could be beneficial clinically; and hence a comparative study was planned. Methods: A prospective, randomized, double blind, comparative, parallel group multicentre study was planned to evaluate the safety and efficacy of FDC of Teneligliptin 20mg + Pioglitazone 15 mg tablets and FDC of Teneligliptin 20mg + Pioglitazone 30mg tablets versus Teneligliptin 20mg and Pioglitazone 30mg alone in patients with type 2 diabetes mellitus (T2DM), inadequately controlled on Metformin. Eight-six patients were recruited in each arm from fifteen centres across India. The primary endpoint was the change in HbA1c from baseline to week 24. Safety was assessed in terms of hypoglycaemic episodes. Results: Patients were matched on demographic and anthropometric parameters. Primary endpoint HbA1c showed significantly more change in FDC groups as compared to monotherapies from baseline to week 12, as well as week 24 (p < 0.0001). On similar lines, FBG and PPBG showed significantly more change in FDC as compared to monotherapies (p < 0.0001). Moreover, the proportion of patients achieving HbA1c < 7% by week 24 was higher in FDC groups as compared to monotherapy groups. Hypoglycaemic episodes were observed in 3.48% cases on dual therapy, while 1.74% on pioglitazone monotherapy and all were of mild severity and resolved by the end of study. Conclusion: The FDC of teneligliptin and pioglitazone has superior and significant control on glycaemic parameters as compared to respective monotherapies and the combination was well tolerated.