Study wrapper · #1208
Once-weekly IcoSema versus once-daily insulin glargine U100 in type 2 diabetes management (COMBINE 4): an open-label, multicentre, treat-to-target, randomised, phase 3b trial.
Editor's note
COMBINE 4 is a well-powered phase 3b randomized trial, and the results land where the mechanism predicts: pairing semaglutide with a once-weekly basal insulin outperformed daily glargine on glucose control, weight, and hypoglycemia risk. The open-label design and Novo Nordisk funding call for the usual careful reading, but the effect sizes — nearly a full percentage point more HbA1c reduction and a 4.6 kg weight difference — are hard to dismiss. For our readers, the signal is semaglutide's continued expansion into once-weekly combination regimens for insulin-naive type 2 diabetes.
Plain-language abstract
In a 40-week trial of 485 adults with type 2 diabetes whose oral medications were no longer keeping blood sugar in range, a once-weekly injection combining basal insulin icodec with semaglutide lowered HbA1c more than daily insulin glargine (a 3.3-point drop versus 2.4). People on the combination also lost a little weight while the glargine group gained nearly 4 kg, and they had about half as many significant low-blood-sugar episodes. Stomach-related side effects were the most common complaint with the combination.