After Metformin, Which Medication Should Be Next for Patients with Type 2 Diabetes?

Selecting a second glucose-lowering agent for patients who are already taking metformin is a commonly encountered decision in clinical practice, but head-to-head comparisons of medications have been limited. Researchers conducted the U.S. multicenter GRADE trial to compare the effect of four medications, added to metformin, in ≈5000 patients with type 2 diabetes.

Participants had recent-onset diabetes (mean duration, 4 years), were taking only metformin, and had baseline glycosylated hemoglobin (HbA_1c) values of 6.8% to 8.5% (mean, 7.5%). Six percent of patients had known cardiovascular disease. Participants were randomized to add a sulfonylurea (glimepiride), a dipeptidyl peptidase-4 (DPP-4) inhibitor (sitagliptin), a glucagon-like peptide-…