Nat Med
Semaglutide drives substantial weight loss after failed bariatric surgery
Clinical takeaway: Semaglutide produced clinically meaningful weight loss in patients who responded poorly to prior bariatric surgery, with most weight loss coming from fat rather than lean mass. The results suggest GLP-1 medication can serve as a less invasive alternative to revisional surgery in this group.
About one in five patients who undergo bariatric surgery either fail to lose enough weight or regain it afterward. Until recently, revisional surgery has been the main effective option, but it's invasive, costly, and not widely available. GLP-1 medications have shown promise in this population, but no randomized trial had tested semaglutide specifically. This study set out to fill that gap.
The trial enrolled 70 adults whose prior bariatric surgery hadn't delivered adequate weight loss, defined as less than 20% loss at least one year after gastric bypass or sleeve gastrectomy. Patients receiving weekly semaglutide lost an average of 18% of body weight at 68 weeks, compared with a 0.4% weight gain in the placebo group, in 70 adults who had less than 20% weight loss at least one year after gastric bypass or sleeve gastrectomy.
In all, 85% of these patients on semaglutide lost at least 10% of their body weight, while 62% lost at least 15% and 47% lost at least 20%.
Body composition analysis showed most of the weight loss came from fat rather than lean tissue, a relevant finding given concerns about GLP-1-induced muscle loss in a population already at risk from prior surgical weight loss. Lean soft tissue as a proportion of total body weight actually increased in the semaglutide group.
Secondary outcomes also benefited. HbA1c, total cholesterol, and triglycerides all improved relative to placebo. Quality-of-life scores improved in domains including physical function, self-esteem, and work.
"These findings strengthen the case for using semaglutide in people who do not respond well to bariatric surgery, offering an alternative to repeat operations," said Janine Makaronidis, MD, of the UCL Centre for Obesity Research and the study's lead investigator. "They also suggest that combining surgery with weight-loss medicines is an important approach to treating severe obesity."
Source: Stanley C. Nat Med. 2026 May 22. Semaglutide versus placebo in individuals with poor weight loss after bariatric surgery: a double-blinded, randomized, placebo-controlled trial