GLP-1 RAs Plus Bariatric Surgery: Promising for Obesity

Combining glucagon-like peptide 1 receptor agonists (GLP-1 RAs) with endoscopic bariatric therapy is a promising way to manage obesity, say the authors of a new review of relevant research.

The review found that adding liraglutide to endoscopic bariatric therapy or bariatric surgery provided significant weight loss when compared with endoscopic bariatric therapy or bariatric surgery alone.

Endoscopic bariatric therapy included intragastric balloon insertion and endoscopic sleeve gastroplasty, and bariatric surgery included Roux-en-Y gastric bypass, gastric sleeve, and laparoscopic sleeve gastrectomy.

According to the findings, liraglutide’s weight loss effect, when combined with endoscopic bariatric therapy, was “comparable” to the net weight loss (ie, nadir weight loss after bariatric surgery minus regained weight) after bariatric surgery alone, first author Ahmad Abdullah Imam, MD, MHSc, with Umm Al-Qura University, Makkah, Saudi Arabia, told Medscape Medical News.

When asked to comment, Steven Grinspoon, MD, with Harvard University and Massachusetts General Hospital, Boston, told Medscape Medical News that though his level of confidence in the data is “not great,” the study raises the “interesting question of whether the GLP-1 RAs could be combined with minimally invasive bariatric surgery techniques.” Grinspoon was not involved in the review.

The study was published online on October 19, 2023 in the Journal of the Endocrine Society.

Comparing Procedures With and Without GLP-1 RAs

There currently is limited evidence on the weight loss effect of combining GLP-1 RAs with endoscopic bariatric therapy or bariatric surgery, which prompted Imam and colleagues to systematically review studies on the topic.

Of the 11 studies included, nine compared bariatric surgery with and without liraglutide, and two compared endoscopic bariatric therapy with or without liraglutide.

Three studies were randomized controlled trials, and eight were retrospective studies. Together, they included a total of 914 participants.

Across all studies, weight change was highest when bariatric surgery was combined with liraglutide (average weight loss, 35.2 kg) and lowest with endoscopic bariatric therapy without liraglutide (average weight loss, 10.2 kg).

In one study, average weight loss was 18.5 kg with endoscopic bariatric therapy plus liraglutide. In a separate study, endoscopic bariatric therapy plus liraglutide yielded 25% total weight loss.

With bariatric surgery alone, average weight loss across six studies ranged from 16.8 kg to 31.8 kg. In one study, bariatric surgery alone yielded 23% total weight loss.

None of the studies examined metabolic changes after endoscopic bariatric therapy plus liraglutide, the researchers note.

The researchers also did not conduct a meta-analysis along with their review due to the limited number of studies included and their significant heterogeneity in design, type of intervention, time of intervention, duration of intervention, and follow-up time.

Despite these limitations, this review highlights a “promising approach” for managing obesity by combining GLP-1 RAs with endoscopic bariatric therapy — one that is expected to come with shorter hospital stays, fewer side effects, and longer-term weight loss benefits than surgery, Imam said.

Though the approach is not yet ready for prime time, “the evidence is growing,” Imam noted.

It’s important to note that liraglutide is a first-generation GLP-1 RA, Grinspoon added. “Now there are second- and third-generation GLP-1 RAs, [with] which you lose more weight.”

“The field is moving toward the question of whether these drugs could take the place of bariatric surgery, with the caveats that there is weight regain after you stop the GLP-1 RA and long-term safety has not been entirely established,” Grinspoon said.

The study had no public or commercial funding. Imam and Grinspoon have no relevant disclosures.

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