In patients with inadequately controlled type 2 diabetes mellitus (T2DM) on dual oral therapy, treatment intensification remains a common clinical challenge. A phase 3 randomized, double-blind, double-dummy trial published in Diabetes, Obesity and Metabolism evaluated whether adding sitagliptin as part of a triple fixed-dose combination (FDC) improves glycemic outcomes compared with continued metformin and higher-dose glimepiride.

The analysis included adult patients with T2DM and glycated hemoglobin (HbA1c) levels of 8%-11% despite metformin and glimepiride therapy. Patients were randomized 1:1 to a triple FDC of sitagliptin 50 mg, metformin 1000 mg, and glimepiride 1 mg (n=190) or co-administered metformin 1000 mg and glimepiride 2 mg (n=202) for 16 weeks. The primary endpoint was the change in HbA1c from baseline to week 16.

At week 16, the least squares mean change in HbA1c was −1.79% (standard error 0.07) with triple FDC versus −1.27% (0.06) with co-administration, with a treatment difference of −0.51% (95% CI −0.69 to −0.33; p<0.0001). HbA1c <7% was achieved in 32.1% versus 12.6% (p<0.0001). Adverse events occurred in 13.2% and 14.9% of patients, respectively.

Overall, triple FDC therapy resulted in greater HbA1c reduction with similar tolerability compared with dual therapy escalation in Indian adults with uncontrolled T2DM.