Weight Loss Surgery, Obesity Drugs Achieve Similar Results

PHILADELPHIA — Roux-en-Y gastric bypass (RYGB) produces maximal weight loss in patients with obesity compared with other surgical procedures and with weight loss drugs, according to a meta-analysis comparing the efficacy and safety of the different treatment options. 

However, tirzepatide, a long-acting glucose-dependent insulinotropic polypeptide (GIP) receptor agonist and glucagon-like peptide-1 receptor agonist (GLP-1 RA), produces comparable weight loss and has a favorable safety profile, reported principal investigator Jena Velji-Ibrahim, MD, MSc, from Prisma Health–Upstate/University of South Carolina School of Medicine in Greenville. 

In addition, there was “no significant difference in percentage total body weight loss between tirzepatide when comparing it to one-anastomosis gastric bypass (OAGB), as well as laparoscopic sleeve gastrectomy,” she said. 

All 11 interventions studied exerted weight loss effects, and side-effect profiles were also deemed largely favorable, particularly for endoscopic interventions, she added. 

“When we compare bariatric surgery to bariatric endoscopy, endoscopic sleeve gastroplasty and transpyloric shuttle offer a minimally invasive alternative with good weight loss outcomes and fewer adverse events,” she said.

Velji-Ibrahim presented the findings (Abstract 46) at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting. 

Comparing Weight Loss Interventions

Many of the studies comparing weight loss interventions to date have been limited by relatively small sample sizes, observational designs, and inconsistent results. This prompted Velji-Ibrahim and her colleagues to conduct what they believe to be the first-of-its-kind meta-analysis on this topic. 

They began by conducting a systematic search of the literature to identify randomized controlled trials (RCTs) that compared the efficacy of US Food and Drug Administration–approved bariatric surgeries, bariatric endoscopies, and medications — against each other or with placebo — in adults with a body mass index of 25-45, with or without concurrent type 2 diabetes. 

A network meta-analysis was then performed to assess the various interventions’ impact on percentage total weight loss and side-effect profiles. P-scores were calculated to rank the treatments and identify the preferred interventions. The duration of therapy was 52 weeks. 

In total, 34 eligible RCTs with 15,660 patients were included. Overall, the RCTs analyzed 11 weight loss treatments, including bariatric surgeries (four studies), bariatric endoscopies (three studies), and medications (four studies). 

Specifically, the bariatric surgeries included RYGB, laparoscopic sleeve gastrectomy, OAGB, and laparoscopic adjustable gastric banding; bariatric endoscopies included endoscopic sleeve gastroplasty, transpyloric shuttle, and intragastric balloon; and medications included tirzepatide, semaglutide, and liraglutide.

Although all interventions were associated with reductions in percentage total weight loss compared with placebo, RYGB led to the greatest reductions (19.29%) and was ranked as the first preferred treatment (97% probability). It was followed in the rankings by OAGB, tirzepatide 15 mg, laparoscopic sleeve gastrectomy, and semaglutide 2.4 mg. 

Tirzepatide 15 mg had a slightly lower percentage total weight loss (15.18%) but a favorable safety profile. There was no significant difference in percentage total weight loss between tirzepatide 15 mg and OAGB (mean difference, 2.97%) or laparoscopic sleeve gastrectomy (mean difference, 0.43%). 

There was also no significant difference in percentage total weight loss between semaglutide 2.4 mg compared with endoscopic sleeve gastroplasty and transpyloric shuttle. 

Endoscopic sleeve, transpyloric shuttle, and intragastric balloon all resulted in weight loss > 5%. 

When compared with bariatric surgery, “endoscopic interventions had a better side-effect profile, with no increased odds of mortality and intensive care needs,” Velji-Ibrahim said. 

When it came to the medications, “the most common side effects were gastrointestinal in nature, which included nausea, vomiting, diarrhea, and constipation,” she said.

Combining, Rather Than Comparing, Therapies

Following the presentation, session co-moderator Shivangi T. Kothari, MD, assistant professor of medicine and associate director of endoscopy at the University of Rochester Medical Center in Rochester, New York, shared her thoughts of what the future of obesity management research might look like. 

It’s not just going to be about percentage total weight loss, she said, but about how well the effect is sustained following the intervention. 

And we might move “away from comparing one modality to another” and instead study combination therapies, “which would be ideal,” said Kothari.

This was the focus of another meta-analysis presented at ACG 2024 (Abstract P3159), in which Nihal Ijaz I. Khan, MD, and colleagues compared the efficacy of endoscopic bariatric treatment alone vs its combined use with GLP-1 RAs.

The researchers identified three retrospective studies with 266 patients, of whom 143 underwent endoscopic bariatric treatment alone (either endoscopic sleeve gastroplasty or intragastric balloon) and 123 had it combined with GLP-1 RAs, specifically liraglutide. 

They reported that superior absolute weight loss was achieved in the group of patients receiving GLP-1 RAs in combination with endoscopic bariatric treatment. The standardized mean difference in body weight loss at treatment follow-up was 0.61 (P

“Further studies are required to evaluate the safety and adverse events comparing these two treatment modalities and to discover differences between comparing the two endoscopic options to various GLP-1 receptor agonists,” Khan noted. 

Neither study had specific funding. Velji-Ibrahim and Khan reported no relevant financial relationships. Kothari reported serving as a consultant for Boston Scientific and Olympus, as well as serving as an advisory committee/board member for Castle Biosciences. 

John Watson is a freelance writer in Philadelphia, Pennsylvania.