Expert Diet and Weight Loss Solutions

CHICAGO Anti-obesity medications and endoscopic sleeve gastroplasty (ESG) are popular strategies for weight loss on their own. Now researchers are looking at what happens when you combine them.

In a study presented at Digestive Disease Week (DDW) 2023, they found ESG followed by an anti-obesity medication led to more total weight loss than ESG alone.

Starting medication within 6 months of ESG was more ideal than other timing intervals. Initiating medical therapy more than 6 months before ESG was associated with less weight loss.

In the single-center, retrospective study, 224 patients were enrolled, of whom 34% were on monotherapy (ESG alone), 31% had combination therapy (medication prescribed within 6 months prior to or after ESG), and 35% had sequential therapy (medication more than 6 months prior to or after ESG).

Most patients were female, ranging from 74% to 95% of each group, and baseline BMI ranged from a mean 37.5 kg/m2 to 40.1 kg/m2.

The medications involved in the study were phentermine, phentermine/topiramate ER (Qsymia), orlistat (Xenical, Alli), bupropion/naltrexone ER (Contrave), or the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide (Saxenda, Victoza) or semaglutide (Ozempic, Wegovy, Rybelsus). Of the patients who underwent combination therapy, 30% were prescribed a regimen that included a GLP-1RA. Of the patients who underwent sequential therapy, 81% were prescribed a medication first and 19% underwent ESG first.

At 1 year, the greatest total weight loss was a mean 23.7% with the combination of ESG and a GLP-1RA. Total weight loss was 18% with ESG plus a non-GLP-1RA medication. ESG alone led to 17.3%. Sequential therapy that began with ESG yielded 14.7% total weight loss, whereas sequential therapy that began with medication first resulted in 12% weight loss.

It's possible that gastroplasty performed second was less impressive because the medications were very effective, and there was not as much weight to lose, said Pichamol Jirapinyo, MD, MPH, a bariatric endoscopist at Brigham and Women's Hospital in Boston, and lead author of the study.

Researchers stopped medication therapy if people did not experience at least 5% total weight loss after 3 months on a maintenance dose.

Waiting for weight loss to start to plateau after gastroplasty might be an ideal time to add weight loss medication, said Jirapinyo. "Usually when I see them at 3 months, I plot how fast their weight loss has been. If it's been going down [steadily], we do not offer an anti-obesity medication until I see them again at 6 months," she said.

The serious adverse event (SAE) rate associated with ESG was similar among the three cohorts: 2.6% with monotherapy group, 1.4% with combination therapy, and 1.3% with sequential therapy. SAEs associated with anti-obesity medication occurred in 1.3% of the sequential therapy group and was not reported in either of the other two groups.

"I certainly think combination therapy should be more effective than just gastroplasty alone and is probably better," said Gregory L. Austin, MD, session co-moderator and a gastroenterologist at the UCHealth Digestive Health Center, Anschutz Medical Campus in Denver, Colorado.

"Whether you start immediately or wait 3 months afterwards is a question that still needs to be answered," he added.

Austin agreed that taking an anti-obesity medicine more than 6 months before gastroplasty might be associated with enough weight loss to make the gastroplasty look less effective.

He also noted that the study "doesn't really address the question of whether you should offer gastroplasty to somebody who's been on [medication] for more than 6 months because you probably still should if they haven't achieved an appropriate weight loss that's associated with reduced comorbidity risk going forward."

In a second study, also presented at DDW 2023, investigators looked at timing of liraglutide for weight loss in a randomized controlled trial. They found that administration of GLP-1RA right after transoral outlet reduction endoscopy (TORe) in people with a history of Roux-en-Y gastric bypass extended weight loss longer than a placebo injection. This strategy was also favorable vs waiting to give liraglutide 1 year later.

Researchers randomly assigned 51 people to get weekly subcutaneous liraglutide injections following TORe for 12 months, then placebo injections for 12 months. They assigned 58 patients to receive weekly placebo injections following TORe for 12 months, then liraglutide injections for 12 months.

At 12 months following the procedure, total body weight loss (TBWL) among participants receiving liraglutide was about 22%, compared with about 14% among patients receiving placebo. At 24 months following the procedure (12 months after crossover), TBWL among patients in the liraglutide-first group was almost 35%, compared with about 24% in the placebo-first/liraglutide-second group.

There was a durable effect associated with liraglutide even after switching to placebo, said Ali Lahooti, lead study author and second year medical student at Weill Cornell Medical College in New York City.

"There did seem to be a better benefit of starting on it for the first year and then stopping it," Austin noted.

These two studies come at a time when the debate over the timing of different obesity interventions continues. Some experts believe weight loss medications can help with the rebound in weight that some people experience months after bariatric surgery, for example.

The study by Jirapinyo and colleagues is "really exciting and interesting," said Linda S. Lee, MD, medical director of endoscopy, Brigham and Women's Hospital in Boston, when asked to comment.

Medication begun within 6 months of the endoscopic procedure "led to superior outcomes compared to just endoscopy alone," Lee said. "I think that's really the wave of the future as far as treating patients with obesity issues. We clearly know that diet and exercise alone for most people is not good enough. Of course, we have surgery, but we also realize that with surgery sometimes the weight starts to creep back up over time."

Lee noted that the study was limited because it was retrospective. Ideally, it would be good if future, prospective research randomly assigns people to endoscopy alone or endoscopy plus medication, she said.

Lee also noted there is a limited number of bariatric endoscopists. By the time people with obesity get to a specialist, they've likely tried diet and exercise and "probably have seen all the commercials for these different medications." I think the reality is that most people will ask their primary care physicians about anti-obesity medication, she said.

"From my point of view, as long as the medicine is safe and not harming them, then let's do both of them together," Lee added.

Lee also mentioned another study [Abstract Mo1898] presented at DDW 2023 that showed total weight loss with endoscopic sleeve gastroplasty was durable over 10 years. Follow-up was with only seven patients, however.

Larger numbers are needed to confirm the finding, but it's "exciting," she said.

Jirapinyo receives grant/research support from Apollo Endosurgery, Fractyl, and USGI Medical, and is a consultant for ERBE, GI Dynamics, and Spatz Medical. Lahooti, Austin, and Lee report no relevant financial relationships.

Digestive Disease Week (DDW) 2023. Abstracts 701 and 703.Presented May 8, 2023.

Damian McNamarais astaffjournalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology and critical care.Follow Damian on Twitter: @MedReporter.

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ESG Plus Obesity Drugs Add Up to More Weight Loss - Medscape