Many adults with obesity and T2D do not reach weight loss on the approved 2.4 mg weekly dose of semaglutide. The STEP UP T2D phase 3b trial, published in The Lancet: Diabetes and Endocrinology, evaluated the efficacy and safety of a higher 7.2 mg dose in 512 participants across 68 centers.

After 72 weeks, semaglutide 7.2 mg produced a mean bodyweight reduction of 13.2% compared with 3.9% with placebo (ETD −9.3%; 95% CI −11.0 to −7.7; P<0.0001). The likelihood of achieving clinically meaningful weight loss (≥5%, ≥10%, ≥15%, ≥20%) was significantly greater with the 7.2 mg dose, with odds ratios ranging from 8.1 to 12.3 (all P<0.001).

Metabolic outcomes also improved, with waist circumference reduced by 6.5 cm and HbA1c lowered by 1.5% versus placebo. Gastrointestinal events were the most frequent adverse events, affecting 53.1% of patients at 7.2 mg, while dysaesthesia occurred more often than with 2.4 mg or placebo. Serious adverse events were reported in around 9% of patients across all groups.

These results suggest semaglutide 7.2 mg provides greater weight and glycemic benefits than the standard 2.4 mg dose. The safety profile was consistent, except for higher rates of dysaesthesia.