VANCOUVER — Glucagon-like peptide-1 (GLP-1) agonists, like semaglutide, liraglutide, and the newly US Food and Drug Administration–approved tirzepatide, not only are gaining popularity among the public for weight loss but also are the focus of considerable attention from gastroenterology researchers.
how they compare to bariatric surgery for weight loss or prevention of metabolic dysfunction–associated steatotic liver disease, and their potential role to prevent regain after weight-loss surgery.
Head-to-Head Comparison
Tirzepatide 15 mg emerged as superior to other GLP-1 agonists for weight loss, for example, in a network meta-analysis of randomized controlled trials looking into obesity management.
Tirzepatide 15 mg was associated with the most effective mean weight loss at just over 15% when Jena Velji-Ibrahim, MD, and colleagues combined data from 14 studies with 18,714 participants with overweight or obesity but without diabetes.
Next up in order of weight-loss efficacy was tirzepatide 10 mg with 13% mean weight loss, semaglutide 2.4 mg with just over 11% mean weight loss, and tirzepatide 5 mg with almost 10% mean weight loss. The only outlier was dulaglutide 0.75 mg, which was linked to about 8% weight gain.
“While clinical trials have been conducted to assess the weight-loss efficacy of GLP-1 agonists, there has been limited head-to-head comparisons, and the data that has been obtained has been quite inconsistent,” Dr. Velji-Ibrahim said when presenting results at the meeting.
Researchers found little difference in efficacies between tirzepatide 15 mg and 10 mg, suggesting both are a viable option for weight loss, said Dr. Velji-Ibrahim of Prisma Health Greenville Memorial Hospital and University of South Carolina School of Medicine in Greenville.
She also reported similar efficacies between oral semaglutide 50 mg and subcutaneous semaglutide 2.4 mg, “meaning that we have another option for weight management.”
Side effects among the different GLP-1 agonists, and among the same agent at different doses, were not significantly different.
Comparison With Bariatric Surgery for Reducing Major Adverse Cardiovascular Events (MACE)
For many years, bariatric surgeons have pointed to the health benefits of weight-loss surgery in the right candidates, including a reduced risk for adverse cardiovascular events.
The weight loss associated with GLP-1 agonists has likewise shown benefits in reducing MACE. However, it remains unclear if one of these weight-loss strategies is better than the other in reducing these outcomes.
To determine this, researchers compared 118,828 people who had bariatric surgery to another propensity-matched group of 118,828 others prescribed GLP-1 agonists. They included adults with a body mass index (BMI) of 35 or higher in the national TriNetX database.
The multicenter, retrospective study revealed bariatric surgery was superior in reducing the risk for heart failure, MACE, and cerebrovascular disease at 3, 5, 7, and 10 years. At 10 years, for example, bariatric surgery was associated with 31% fewer composite cardiovascular events than the GLP-1 agonists.
“Our results suggest that bariatric surgery is more effective than GLP-1 analogs in preventing adverse cardiovascular events in obese patients,” Ayowumi A. Adekolu, MD, an internal medicine resident at West Virginia School of Medicine in Morgantown, said in audio comments accompanying his ePoster at the meeting. “Although these findings highlight the benefit of bariatric surgery in mitigating adverse cardiovascular events, well-designed prospective studies are necessary to confirm these benefits in this patient population.”