Taking semaglutide before bariatric surgery does not improve weight loss or safety

Mass General Brigham researchers found that total weight loss did not increase for patients who took semaglutide before having weight loss surgery, suggesting that a surgery first strategy could lead to better outcomes

A new study from Mass General Brigham could help inform conversations between providers and patients who are considering whether to try weight loss medications or surgery first. Researchers studied whether taking semaglutide, one of the new glucagon-like peptide-1 agonist (GLP-1 RAs) drugs, also known as Ozempic and Wegovy, before bariatric surgery could help patients with obesity and metabolic disease lose weight. But the retrospective study of 350 patients revealed that taking semaglutide before bariatric surgery did not improve overall weight loss or safety outcomes compared to surgery alone. The findings, published in JAMA Surgery, suggest that a surgery-first strategy may lead to better overall obesity treatment outcomes for patients.

“Many people are familiar with the new GLP-1 medicines that are available. These drugs are good options for patients to consider, and they can be used in combination with surgery,” said senior author Eric G. Sheu, MD, PhD, of the Laboratory for Surgical and Metabolic Research and chief of the Section of Bariatric and Foregut Surgery at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system. “You might expect patients to lose more weight if they take a medication prior to surgery. But we were surprised to find that the group of patients who went on medicines first and then had surgery actually had the same combined total weight loss. This contrasts with previous studies that have found that taking semaglutide after surgery can further help patients lose weight.”

Patients exploring weight-loss management strategies may elect to undergo bariatric surgery, which is the most effective and durable treatment to lose weight and reduce the risk of death from heart disease, stroke, cancer and diabetes. Previous studies have found that taking semaglutide after weight loss surgery may be effective to help lose more weight or maintain weight, although additional research is needed. The effectiveness of taking semaglutide before weight loss surgery was unknown.

Using data from the Brigham’s Center for Weight Management and Wellness, the researchers retrospectively identified 182 patients over the last seven years who were treated with semaglutide before undergoing bariatric surgery. They matched each of the patients to another patient with similar health characteristics that underwent the same type of surgery without previously taking the drugs. The study team compared the amount of weight lost, health outcomes and safety outcomes between the groups.

The researchers found that patients who took the semaglutide before surgery had a higher percentage of total weight loss at three months than patients who had weight loss surgery only. But the surgery-only group rapidly caught up, and total weight loss for the group that had received semaglutide before surgery plateaued at the same percent lost at the six-, nine-, and 12-month marks.

The researchers also found that the number and degree of safety events were similar for both groups, with no significant difference in major postoperative complications, including bleeding, leakage, infection, re-operation, re-admission or operative time. Health outcomes were also comparable between the groups, with similar levels of diabetes remission after one year.

“We are trying to figure out the best timing for these strategies to maximize their effectiveness and safety. When a patient should start the medicine, when they should stop taking it before surgery, and when they should have the surgery are things that still need to be evaluated,” said Sheu. “We also need to understand if the type of bariatric surgery matters for how patients respond to the medicines.”

Prospective studies will be an important tool for answering these questions in the future.

“We will need to conduct more research to answer the remaining questions, but there's at least a suggestion that the most effective weight loss strategy isn’t as simple as 1 + 1 = 2,” Sheu said. “The order of strategies may be key.”

Authorship: In addition to Sheu, Mass General Brigham authors include Vasundhara Mathur, Katherine Wasden, Thomas Shin, Pourya Medhati, Abdelrahman Nimeri and Ali Tavakkoli.

Disclosures: Nimeri reported being an advisory board member for Ethicon outside the submitted work. Tavakkoli reported being cofounder and consultant for AltrixBio during the conduct of the study. Sheu reported receiving personal fees from Cine-Med and Vicarious Surgical, nonfinancial support from Intuitive Surgical, and grants from National Institutes of Health outside the submitted work; holding 3 pending patents for CA7S and related pathways for treatment of obesity and diabetes.

Paper cited: Mathur, V et al. “‘Neo-adjuvant’ semaglutide reduces weight loss with bariatric surgery and does not improve overall outcomes” JAMA Surgery DOI:  10.1001/jamasurg.2025.0001

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