Drugs vs surgery for weight loss: The better of 2 options

In a first-of-a-kind meta-analysis comparing the efficacy and safety of different treatment options for obesity, weight loss surgery using the Roux-en-Y gastric bypass (RYGB) yields optimal weight loss than other surgical procedures or weight loss medications.

“As for tirzepatide, this long-acting dual GIP and GLP-1* receptor agonist performed just as well, with favourable safety profile,” reported principal investigator Dr Jena Velji-Ibrahim from Prisma Health–Upstate/University of South Carolina School of Medicine in Greenville, South Carolina, US at the recent American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

“There was no significant difference in total body weight loss percentage between tirzepatide and one-anastomosis gastric bypass (OAGB), as well as laparoscopic sleeve gastrectomy,” she added. 

All 11 interventions studied produced weight loss effects, and side-effect profiles were largely favourable, particularly for endoscopic interventions.

Surgery vs medication

Velji-Ibrahim and colleagues conducted a literature search to identify randomized controlled trials (RCTs) comparing the efficacy of US FDA–approved bariatric surgeries, bariatric endoscopies, and medications in adults with a BMI of 25–45 kg/m², with or without type 2 diabetes. [ACG 2024, abstract 46]

After that, a network meta-analysis was performed to assess the impact of the various interventions on the percentage of total weight loss and side-effect profiles. P-scores were calculated to rank the treatments and identify the preferred interventions. The therapy lasted for 52 weeks.

Overall, 34 RCTs with 15,660 patients were included in the analysis. The RCTs analysed weight loss treatments, including bariatric surgeries (four studies), bariatric endoscopies (three studies), and medications (four studies).

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. As for weight loss medications, tirzepatide, semaglutide, and liraglutide were included.

Battle of winners

“When comparing bariatric surgery with bariatric endoscopy, endoscopic sleeve gastroplasty and transpyloric shuttle provided a minimally invasive alternative, with good weight loss outcomes and fewer adverse events,”  said Velji-Ibrahim.

She noted that current studies comparing weight loss interventions have been limited by relatively small sample sizes, observational designs, and conflicting outcomes. Velji-Ibrahim said the meta-analysis was borne out of this need.

Treatment of choice

“Although all interventions were associated with reductions in the percentage of total weight loss compared with placebo, RYGB led to the greatest reductions (19.29 percent) in weight and was ranked as the most preferred treatment (97 percent probability),” she reported.

RYGB was followed by OAGB, tirzepatide 15 mg, laparoscopic sleeve gastrectomy, and semaglutide 2.4 mg. 

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

Additionally, no significant difference was found in total weight loss percentage 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 of >5 percent. 

“Compared with bariatric surgery, endoscopic interventions had a better side-effect profile, with no increased odds of mortality and intensive care requirements,” Velji-Ibrahim pointed out. 

“As for medications, the most common side effects were gastrointestinal in nature, which included nausea, vomiting, diarrhoea, and constipation,” she added.

Combination modalities

Session co-moderator Dr Shivangi Kothari from the University of Rochester Medical Center in Rochester, New York, US, however, said the future of obesity management is not just about weight loss percentage, “rather, it will be about how well weight loss is sustained post-intervention.”

“The future will be about moving away from comparing one modality or intervention to another. Instead, we should be looking at combination therapies in future trials, which could be the best intervention for patients with obesity,” she emphasized.

Endoscopic bariatric surgery + GLP-1 RA

Kothari’s aspirations were not that far off. A separate systematic review of the literature, also presented at ACG 2024, analysed the combination of endoscopic bariatric intervention (endoscopic sleeve gastroplasty or intragastric balloon) plus a GLP-1 RA vs endoscopic bariatric therapy alone in patients with obesity.

Three retrospective studies involving 266 patients, 143 of whom underwent endoscopic bariatric treatment alone, were analysed. They were compared with 123 patients treated with bariatric surgery and a GLP-1 RA, specifically liraglutide. [ACG 2024, abstract P3159]

The outcome of interest was the standardized mean difference (SMD) of the mean absolute body weight loss during follow-up.

“Both pharmacologic and surgical treatments are effective treatment options for obesity,” said study author Dr Nihal Ijaz Khan from AdventHealth Medical Group, AdventHealth, Orlando, Florida, US. “Our analysis shows the superior absolute weight loss achieved by patients receiving GLP-1 RAs in combination with endoscopic bariatric treatment compared with endoscopic bariatric treatment alone.”

The SMD in body weight loss between endoscopic bariatric treatment + GLP-1 RA and endoscopic bariatric treatment alone at follow-up was 0.61 (95 percent confidence interval [CI], 0.35-0.86; p<0.01; I2 of 91 percent).

“Further studies are warranted to evaluate the safety and adverse events comparing these two treatment modalities,” said Khan. “These could also uncover the differences between comparing the two endoscopic options to various GLP-1 RAs,” he concluded.