Patients with type 2 diabetes mellitus (T2DM) often require treatment intensification when dual oral therapy does not achieve glycemic targets. A multicenter, randomized, double-blind, placebo-controlled phase 3 trial, published in Diabetes Research and Clinical Practice, evaluated anagliptin added to metformin and empagliflozin in patients with inadequate glycemic control.

The trial enrolled adults with T2DM and glycated hemoglobin (HbA1c) 7.0% to 11.0% who were receiving metformin at least 1000 mg/day and empagliflozin 25 mg/day. Participants were randomized 1:1 to anagliptin 100 mg twice daily or placebo for 24 weeks, followed by a 28-week open-label extension. The primary endpoint was change in HbA1c from baseline to week 24. Of 200 randomized patients, 197 were included in the efficacy analysis. Baseline HbA1c was 7.76%.

At week 24, least-squares mean HbA1c changed by −0.83% with anagliptin and −0.03% with placebo. The between-group difference was −0.80% (95% CI −0.95 to −0.64; P<0.0001). Least-squares mean change in homeostasis model assessment of beta-cell function (HOMA-β) was +10.45 with anagliptin and −6.02 with placebo, with a between-group difference of 16.46 (P=0.0003).

Adverse event rates were similar between groups, and no severe hypoglycemia or deaths were reported. These findings support anagliptin added to metformin plus empagliflozin as a potential oral intensification option in appropriately selected patients.