GLP-1s and Bariatric Surgery: Before, After, or Both?

Results from a new study showed no apparent benefit in total weight loss when patients are treated with the glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide prior to bariatric surgery, adding to the data on if and when weight loss drugs should be used in conjunction with surgery.

While the findings suggested patients choosing bariatric surgery may be better off skipping pretreatment with antiobesity medication, lead 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, Boston, noted that guidelines regarding the practice are lacking.

As the popularity of highly effective antiobesity drugs has soared and rates of bariatric surgery have declined, questions about the benefit of using both, particularly in terms of weight loss maintenance, have arisen. Among the key issues is the best timing of the drugs to improve outcomes — before or after surgery, or both.

The current study suggested “that the sequence and timing of semaglutide and metabolic bariatric surgery affect outcomes, challenging the concept that any combination of medicine and surgery has additive effectiveness,” the study authors wrote in a research letter, published earlier this month in JAMA Surgery.

Previous research supporting the benefits of antiobesity drugs with bariatric surgery includes a study of 98 patients who showed significant improvements in weight loss when both pre- and postoperative antiobesity drugs were used compared with bariatric surgery alone.

To further investigate the long-term outcomes of neoadjuvant semaglutide, Sheu and colleagues conducted a retrospective, case-control study between 2017 and 2024, evaluating patients with severe obesity who were undergoing bariatric surgery, primarily sleeve gastrectomy.

The patients were matched 1:1 in groups of 182 each, using propensity score matching based on whether they received semaglutide prior to bariatric surgery.

Patients were matched by age, race, preoperative body mass index (BMI), diabetes status, and surgical procedure. Those in the preoperative semaglutide group received the treatment for a median of 24.4 weeks.

About 77% of patients were women; their median age at surgery was 45 years, and their median preoperative BMI was approximately 43 in both groups.

While those who received preoperative semaglutide had a higher percentage of total body weight loss at 3 months, the surgery-only group caught up and had significantly greater total weight loss at postoperative months 6, 9, and 12, with a median 12-month total weight loss of 26% vs 21% (P = .008).

In the pretreatment period before bariatric surgery, patients receiving semaglutide had a median total weight loss of 4.0%. A further analysis of total weight loss that included the weight loss during that period also showed a higher weight loss with the preoperative semaglutide group at 3 months but no significant differences in weight loss between the two groups thereafter.

There were no significant differences in median A1c levels between the semaglutide group vs control patients before surgery (5.8% vs 6.0%; P = .15) and 1 year after surgery (5.5% vs 5.7%; P = .60), and rates of diabetes remission at 1-year postsurgery were also similar (12.6% vs 5.1%; P = .15).

The authors noted that the results are consistent with previous studies evaluating prebariatric surgery treatment without GLP-1 drugs, which also showed no benefits in increasing overall weight loss or safety.

No Guidelines Regarding GLP-1s With Bariatric Surgery

“There is no established consensus or society guideline on who should proceed directly to surgery, who should try medications, or for how long or how many medications you should try without success before going to surgery,” Sheu told Medscape Medical News.

In clinical practice, patients at very high weights and BMI are often prescribed neoadjuvant GLP-1 to try to improve the safety of surgery and to improve overall weight loss, he noted.

However, “our study findings call that practice into question, with the large caveat that we did not have many patients in our study with very high BMI.”

Overall, “surgery is the more effective and durable obesity and diabetes therapy, even compared to the GLP-1s,” he added.

Data support this — the expected weight loss from bariatric surgery ranges from 25% to 33% for the two most common operations compared with approximately 15%-20% with GLP-1 receptor agonists.

“At our center, we do believe that patients at higher BMIs or with significant associated medical conditions such as diabetes should consider surgery first,” Sheu said.

Limitations: Current Weight Loss Doses Typically Higher

Semaglutide was only approved for diabetes until 2021, and the average dose in the study was just 1.0 mg, Sheu noted. Higher doses commonly used for weight loss were only used after the US Food and Drug Administration approval for obesity.

However, the researcher speculates that even with the higher doses, the outcomes may be similar.

“My prediction is that the weight loss pattern in our study would be the same even with sustained obesity treatment dosages of semaglutide and with tirzepatide — ie, total weight loss would be the same with medications plus surgery as with surgery alone,” he said.

“You would just see more of the total weight loss come from the medication arm of treatment with tirzepatide or Wegovy doses of semaglutide,” he added.

Another limitation is the fact that patients with a good semaglutide response may not feel the need to undergo bariatric surgery; hence, the study could suffer from selection bias.

And with the cohort mainly made up of patients undergoing sleeve gastrectomy, the results do not extend to other bariatric operations, such as Roux-en-Y gastric bypass.

Hope That GLP-1s Will ‘Push the Envelope’ for Bariatric Surgery Weight Loss

Commenting on the study, Jason M. Samuels, MD, an assistant professor of surgery in the Section of Surgical Sciences, Division of General Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, noted a further limitation.

The presurgery weight loss in the semaglutide group of just 4% over 24 weeks “was dramatically lower than what was described in the STEP trials” — approximately 10% in trial patients — “suggesting that semaglutide had minimal impact on weight loss in the treated arm.”

A lack of data regarding whether prescriptions were actually filled is a further limitation, particularly with issues of semaglutide shortages and tolerability issues, Samuels told Medscape Medical News.

Nevertheless, there is high interest in the potentially profound benefit that GLP-1s could have in bariatric surgery, he said.

“There is great hope for just this possibility, that GLP-1 receptor agonists will help bariatric surgeons safely push the envelope in terms of what weight loss is achievable, or at the very least, further improve the safety of what have become incredibly safe surgeries thanks to the efforts of [bariatric surgery quality improvement programs],” he said.

Regarding postoperative GLP-1s, Samuels noted his team is conducting an ongoing clinical trial looking at the effects of the dual GLP-1/glucose-dependent-insulinotropic polypeptide tirzepatide in enhancing weight loss after gastric bypass in patients with persistent obesity (BMI > 30) at 1 year after gastric bypass surgery.

His study will look at the effects of earlier initiation of the drugs, as these drugs are most commonly used when patients experience weight regain or inadequate weight loss several years after surgery.

“No real-world evidence exists regarding whether patients who have expected weight loss after surgery would be able to achieve more weight loss with GLP-1s when initiated early after surgery,” Samuels said.

“We anticipate the trial concluding in about 2 years and hope to demonstrate that early implementation of these medications is safe and further enhances weight loss in this population.”

Higher BMI Typical for Bariatric Surgery

Further commenting on the study, Salim Abunnaja, MD, who was senior author on the study, a diplomate of the American Board of Obesity Medicine and associate professor of surgery at West Virginia University School of Medicine, Morgantown, West Virginia, that showed significant improvements in weight loss with both pre- and postoperative antiobesity drugs, agreed that “most bariatric specialists only consider preoperative GLP-1s for patients with a BMI of 55 or above.”

“This supports the idea that many patients weren’t deliberately placed on GLP-1s as a planned step before surgery,” said Abunnaja.

Abunnaja explained that in his practice, GLP-1s are used in patients with more severe obesity (eg, BMI > 60) for about 3-6 months preoperatively, and the medication is then resumed around 6-12 weeks after surgery.

“In our experience, combining surgery and ongoing GLP-1 therapy leads to better weight loss and few additional side effects — often the side-effect profile is even better post-op,” he said.

Ultimately, “for clinicians who choose to use GLP-1 preoperatively, planning to resume it postsurgery is key to maximizing outcomes,” he said.

BMI-Guided Approach to GLP-1/Bariatric Surgery Decisions

In addition, a structured approach, similar to cancer staging and management, is used in GLP-1 therapy and surgery based on the level of BMI, said Abunnaja.

• BMI < 35 (Class I obesity): “GLP-1s alone often suffice,” he said.
• BMI between 35 and 55 (Class II or early Class III): “Surgery typically provides excellent outcomes on its own, with GLP-1s or other medications introduced afterward if results are suboptimal.”
• BMI ≥ 55 (Severe obesity): “We employ medications before surgery, then proceed with surgery, and add medications again 3 months afterward.”

“In this framework, once patients understand that medication alone may not provide the full benefit they need, most remain committed to proceeding with surgery, even if they experience some initial weight loss with GLP-1s,” Abunnaja said.

Sheu reported receiving personal fees from CineMed and Vicarious Surgical, nonfinancial support from Intuitive Surgical, and grants from the National Institutes of Health outside the submitted work. He holds three pending patents for CA7S and related pathways for the treatment of obesity and diabetes. Abunnaja and Samuels had no disclosures to report.