- GLP-1 agonists and bariatric surgery are top obesity treatments, raising questions of their combined efficacy.
- A retrospective study found that patients taking GLP-1 drugs before surgery achieved similar 12-month weight loss as non-users (24% vs 25%).
- Treatment groups had comparable outcomes on surgical complications and diabetes control.
Bariatric surgery patients who took GLP-1 medications prior to surgery lost the same amount of weight after 1 year as individuals unexposed to the blockbuster class of drugs, a retrospective review indicated.
Among 383 patients, those who took a GLP-1 drug before surgery lost 24% of their total body weight at 12 months, while non-users lost 25% (P=0.33), reported Jonathan Carter, MD, of the University of California San Francisco, and colleagues in JAMA Surgery.
Average postsurgical weight loss didn’t differ either, at 66 lb (30 kg) and 71 lb (32 kg), respectively (P=0.34). No differences were noted in diabetes control or complications.
“With the rise of GLP-1 receptor agonists for obesity treatment, questions have emerged about potential synergy with bariatric surgery,” the authors wrote. “Many patients now present for surgery already taking these medications, prompting investigation into their impact on outcomes.”
Carter told MedPage Today that he was slightly surprised by the findings, as there was the possibility that preoperative GLP-1 drug use might “steal” from surgical weight loss later on, given that one mechanism of bariatric surgery is GLP-1 augmentation.
“In our study, we saw no such effect,” he said. “Those taking GLP-1 receptor agonists, who presumably lost weight from the medications before surgery, turned out to lose additional weight the same as the GLP-1 receptor agonist-naive patients.”
He noted that patients on GLP-1 drugs can still achieve “terrific results” with surgery. “It is not a zero-sum game. We should not think of obesity treatment as a competition between medicine and surgery.”
The findings align with two recent retrospective studies that showed no difference in 12-month postoperative weight loss between GLP-1 drug users and non-users. However, another study found that patients who took preoperative semaglutide lost comparatively less weight after surgery than GLP-1-naive patients at 12 months (21% vs 26%, P=0.008).
“Since we have conflicting studies, we need additional studies with larger cohorts of patients,” said Carter, adding that research is also needed to determine optimal treatment sequencing.
“Anecdotally, we have had many patients add a GLP-1 receptor agonist years after bariatric surgery with terrific results, often achieving weights in the normal or near-normal range. As time goes on, we will learn how best to combine and sequence obesity therapy to optimize results for our patients,” he added.
For the study, Carter’s group analyzed primary bariatric surgeries at a single center from 2022 to 2024 (92 GLP-1 users and 291 non-users). Average age was 44 years, 80% were female, and their baseline body mass index (BMI) was around 44. Patients predominantly underwent sleeve gastrectomy (83-88%) rather than gastric bypass (12-17%).
Preoperative GLP-1 agents included oral semaglutide (Rybelsus), injectable semaglutide (Ozempic, Wegovy), dulaglutide (Trulicity), liraglutide (Victoza, Saxenda), and tirzepatide (Mounjaro, Zepbound). Most patients took semaglutide (63%); few were on tirzepatide (4%). The majority were not at the maximum dose.
Groups had similar baseline characteristics other than that more GLP-1 drug users than non-users had diabetes (51% vs 16%), while fewer smoked (3% vs 11%), and the GLP-1 drug group averaged higher baseline HbA1c (6.5% vs 5.7%).
A multivariate regression confirmed preoperative GLP-1 agonist use was not a predictor of total weight loss (β=-0.17, P=0.89). Operative time, length of stay, 30-day emergency department visits, and complications were similar between groups. Excellent 12-month HbA1c control was also achieved in both groups (5.4% vs 5.3%).
Higher baseline BMI (β=0.29) and male sex (β=2.67) independently predicted greater weight loss, while diabetes (β=-4.49) and sleeve gastrectomy (β=-4.72) predicted less weight loss.
Discontinuation of GLP-1 drugs was recommended after surgery to prevent vomiting. Only 15 patients resumed therapy postsurgery: five for diabetes management, eight for weight control, and two for unknown reasons. These patients had comparable 12-month weight loss to non-users (22% vs 25%, P=0.51).
The analysis was limited by an inability to quantify preoperative weight loss from GLP-1 drugs and treatment duration. Sample size constraints also prevented comparisons between bariatric procedures.
“The data … will evolve over time with larger studies, newer drugs, and better understanding of how much weight was lost at medicine initiation and then surgery,” Carter concluded. “My guess is that we will learn that combination therapy, with medicine and surgery, will outperform either one alone.”
