Achieving glycemic targets remains challenging for many patients with T2DM despite dual therapy. A phase 3 multicenter, double-blind, randomized study, published in the Diabetes & Metabolism Journal, evaluated whether adding pioglitazone 30 mg/day could enhance glucose control in patients inadequately managed on dapagliflozin and metformin.

Across 34 study sites, 246 participants were randomized to receive pioglitazone or placebo for 24 weeks. HbA1c levels significantly decreased in the pioglitazone group (from 7.8% ± 0.8% to 7.0% ± 0.6%; p < 0.0001), while minimal change occurred with placebo. More than half achieved HbA1c <7%, and 22% reached <6.5%.

The regimen was well tolerated, with modest weight gain (2.0 kg) and low edema rates. These findings highlight that adding pioglitazone to dapagliflozin and metformin can effectively improve glycemic outcomes without compromising safety, offering a practical next-step option for patients with suboptimal control on dual therapy.