Patients treated with GLP-1 receptor agonists prior to bariatric surgery show no significant differences in postsurgical weight loss compared with untreated control individuals, new research showed.

The findings underscore that “patients on GLP-1s can go on to have terrific results with bariatric surgery to lose additional weight,” senior author Jonathan Carter, MD, of the Department of Surgery, University of California, San Francisco, told Medscape Medical News.

“It is not a zero-sum game — the weight loss of GLP-1s and then bariatric surgery seem to be additive,” he added. “We should not think of obesity treatment as a competition between medicine and surgery. Rather, combination therapy is proving to be the best for our patients.”

The study was published as a research letter in JAMA Surgery.

As GLP-1 use for weight loss becomes ever more mainstream, prior treatment with the drugs is increasingly common in patients receiving bariatric surgery, however, research is lacking on how or if the prior treatment influences bariatric surgery outcomes.

To investigate, Carter and colleagues conducted a retrospective review of all patients undergoing bariatric surgery at their center between 2022 and 2024.

Of the 383 patients included in the study, 92 (24%) were previously treated with GLP-1s or the dual GLP-1/glucose insulinotropic polypeptide drug tirzepatide.

The most commonly used GLP-1 drug in the study group was semaglutide (63%), and just four patients (4%) were treated with tirzepatide.

The median semaglutide dose was relatively low, at just 1 mg (range, 0.25-4 mg), and the median dose for tirzepatide was 3.75 mg (2.5-7.5 mg).

Patients overall had a mean age of 44 years, with no significant differences in gender (80% female among those not previously taking GLP-1s and 78% in those previously taking the drugs), in mean baseline mean BMI (BMI, 44 and 43, respectively), or other characteristics.

Of note, just 16% of those not treated with GLP-1s had diabetes vs 51% of those with prior GLP-1 use.

Following bariatric surgery, no significant differences were observed between the groups in terms of the percentage of total weight loss at 12 months (mean, 25% with no prior GLP-1 use vs 24% with prior GLP-1 use; P = .330), nor were there differences in the mean percentage of excess body weight loss at 12 months (60% vs 62%; P = .650).

After a multivariate adjustment for factors including age, BMI, sex, race and ethnicity, diabetes, smoking status, and procedure, prior GLP-1 use remained as not being a predictive factor of percentage of 12-month total weight loss (P = .890).

Factors that were independently associated with greater total weight loss included having a higher baseline BMI (beta = 0.29; P < .001) and male sex (beta = 2.67; P = .014).

Meanwhile, factors significantly associated with lower total body weight loss included diabetes (beta = -4.49; P < .001) and surgery with sleeve gastrectomy (beta = −4.72; P < .001).

There were not significant differences between the groups in other outcomes, including operative time, length of stay, 30-day emergency department visits, or complications between the two groups.

Of note, both groups had excellent control of diabetes, as assessed by A1c levels, at 12 months (mean, 5.4% vs 5.3%; P = .440).

Resuming GLP-1s

A small subset of 15 patients did resume GLP-1 therapy within the 12 months following surgery, including five for diabetes management, eight for weight control, and two for unknown reasons. 

Among those patients, the mean 12-month total weight loss percentage was 22%, which was not significantly different from patients who were not taking GLP-1s (mean, 25%; P = .510).

Carter noted that those findings offer some reassurance in terms of the effects of bariatric surgery in helping to continue to manage diabetes in patients discontinuing GLP-1s for the surgery.

“Although discontinuing the GLP-1 might worsen diabetes if it were done in isolation, adding bariatric surgery profoundly improves diabetes and induces remission in many regardless of whether the GLP-1 was restarted after surgery,” he explained.

“Indeed, only five out of 93 diabetic patients were put on a GLP-1 after surgery, even though 47 were on GLP-1s before surgery,” Carter said.

“So the 42 people with diabetes who kept off GLP-1s achieved normal or near normal A1c levels from the surgery itself.”

No Effects in GLP-1 Weight Loss Lessening Bariatric Surgery Effects

Overall, Carter said the lack of a significant difference between those who did and did not receive prior GLP-1s in terms of bariatric surgery-related weight loss was a “slight surprise.”

“Given that one mechanism of how bariatric surgery works is via GLP-1 augmentation, I thought that weight loss in patients on GLP-1s taken preoperatively might ‘steal’ from the weight loss we see later with the surgery,” he explained.

“In our study we saw no such effect — those taking GLP-1s, who presumably lost weight from the medications before surgery, turned out to lose additional weight the same as the GLP-1-naive patients.”

Key caveats include that most patients in the study were on semaglutide, with very few on tirzepatide. and the prior amount of GLP-1-related weight loss and duration of therapy were not known.

“The data on this question will evolve over time with larger studies, newer drugs, and better understanding how much weight was lost at medicine initiation and then surgery,” Carter said.

“My guess is that we will learn that combination therapy, with medicine and surgery, will outperform either therapy alone.”

Findings Consistent, but More Data Needed

Other research supporting the current findings include a study of 2169 patients in Indiana and another study of 422 patients at Rush University Medical Center in Chicago, each showing no significant differences in weight loss at 12 months after bariatric surgery among those who were and were not previously treated with GLP-1s.

In a study of more than 9000 patients in the nationwide Epic Cosmos nationwide database, presented in May at the annual meeting of the American Society for Metabolic and Bariatric Surgery, rates of weight loss without vs with prior GLP-1 use were higher up to 3 years after bariatric surgery among those receiving gastric bypass surgery vs sleeve gastrectomy.

In general, however, “when we restricted the patients to those who had already lost weight on GLP-1s, we found that overall, their total weight was similar to patients who just came into surgery as a primary strategy,” co-author Karan R. Chhabra, MD, an assistant professor of surgery and population health at the NYU Grossman School of Medicine, New York City, told Medscape Medical News.

Moving Toward a ‘Comprehensive Treatment Model’

Commenting on the current study, Chhabra said the collective findings support benefits of continued weight loss in transitioning from GLP-1 use to bariatric surgery.

“I think based on this paper and other papers, we now know that patients can still expect good weight loss if they’re getting bariatric surgery after having been under GLP-1s in general,” he said. “We still need further research on the patients who don’t respond to GLP-1s, regarding whether bariatric surgery is still a good fit for them, and that’s something that our team is working on figuring out as well.”

Chhabra echoed Carter’s assessment: “All in all, I think that treatment of obesity is moving toward a comprehensive treatment model that includes medications, surgery, and even endoscopic procedures.”

The authors and Chhabra had no disclosures to report relating to the studies.