ECO 2026
Higher-dose semaglutide nears 28% weight loss in early responders
Clinical Takeaway: In adults with obesity, higher-dose semaglutide 7.2 mg produced greater and faster weight loss than semaglutide 2.4 mg while largely preserving muscle function. Early response may help clinicians counsel patients on expected long-term outcomes, but meaningful weight loss was still seen in non–early responders.
New analyses from the phase 3b STEP UP trial, presented at the 2026 European Congress on Obesity, provide additional insight into weight-loss trajectories and body composition changes with higher-dose semaglutide. The trial enrolled more than 1,400 adults with obesity without type 2 diabetes and compared weekly semaglutide 7.2 mg, semaglutide 2.4 mg, and placebo over 72 weeks.
Overall, patients receiving semaglutide 7.2 mg lost a mean 20.7% of body weight, versus 17.5% with semaglutide 2.4 mg and 2.4% with placebo. Among ‘early responders’ — defined as patients achieving ≥15% weight loss by week 24 — mean weight loss reached 27.7% at week 72 with semaglutide 7.2 mg, compared with 24.8% with semaglutide 2.4 mg. Early response was observed in 27% of patients receiving semaglutide 7.2 mg and 21% receiving semaglutide 2.4 mg.
A secondary MRI-based substudy in 55 participants found that 84% of weight loss with semaglutide came from reductions in fat mass. Visceral abdominal fat decreased by more than 30%, an important marker of cardiometabolic health. Muscle mass declined by about 10% from baseline, but muscle quality improved based on reductions in intramuscular fat. Functional muscle strength was also preserved despite substantial weight loss. This was measured using a 30-second sit-to-stand test. The findings suggest semaglutide preferentially reduced fat while preserving functional muscle strength. Safety and tolerability were consistent with the established semaglutide 2.4 mg profile.
"Early weight loss may indicate who is likely to achieve the most weight loss from semaglutide," said Dr. Dror Dicker, of Tel-Aviv University, Israel. "These new insights from the STEP UP sub-analysis presented at ECO can help healthcare professionals with managing expectations and setting goals with their patients when initiating obesity medications and potentially support long-term persistence to treatments."
Source: Novo Nordisk. (2026, May 11). Press release. Novo Nordisk A/S: Higher dose Wegovy demonstrates nearly 28% weight loss in early responders according to new analyses presented at the European Congress on Obesity