Alogliptin as a third oral antidiabetic drug in patients with type 2 diabetes and inadequate glycaemic control on metformin and pioglitazone: a 52-week, randomized, double-blind, active-controlled, parallel-group study

Aim: To assess the efficacy and safety of adding alogliptin versus uptitrating pioglitazone in patients with type 2 diabetes and inadequate glycaemic control on metformin and pioglitazone. Methods: In this randomized, double-blind, active-controlled, parallel-group study, patients with type 2 diabetes and A1c >= 7.0 and >= 10.0% on metformin (>= 1500 mg or maximum tolerated dose; Met) and pioglitazone 30 mg ( Pio30) received alogliptin 25 mg (Alo25; n = 404) or pioglitazone 15 mg ( n = 399) added to Met+Pio30 for 52 weeks. The primary endpoint was change from baseline (CFB) in A1c at weeks 26 and 52, with sequential testing for non-inferiority of Met+Pio30+Alo25 at weeks 26 and 52 and then for superiority at week 52. Results: Met+Pio30+Alo25 showed superior glycaemic control versus Met+Pio45 at week 52 [least squares (LS) mean CFB in A1c, -0.70 vs. -0.29%; p < 0.001]. At week 52, Met+Pio30+Alo25 resulted in greater CFB in A1c regardless of baseline A1c ( p < 0.001); higher proportions of patients achieving A1c = 7.0 (33.2 vs. 21.3%) and = 6.5% (8.7 vs. 4.3%; p < 0.001); greater CFB in fasting plasma glucose (FPG; LS mean CFB, -0.8 vs. -0.2 mmol/L; p < 0.001); and greater improvements in measures of beta-cell function ( p < 0.001). Hypoglycaemia incidence was low (Met+Pio30+Alo25, 4.5%; Met+Pio45, 1.5%), mostly mild to moderate, but with two severe events in the Met+Pio30+Alo25 group. No meaningful differences in incidences of individual adverse events were observed between treatments. Conclusions: Adding alogliptin to an existing metformin-pioglitazone regimen provided superior glycaemic control and potentially improved beta-cell function versus uptitrating pioglitazone in patients with type 2 diabetes, with no clinically important differences in safety.