Metabolic surgery was associated with lower all-cause mortality and a lower risk for major adverse cardiac events than GLP-1 receptor agonists (RAs), based on data from a new study of more than 3000 individuals with obesity and type 2 diabetes (T2D).
“With GLP-1 medicines widely available and highly effective,” many have questioned “whether bariatric surgery still offered added value,” said corresponding author Ali Aminian, MD, primary investigator of the study and director of the Bariatric and Metabolic Institute at the Cleveland Clinic, Cleveland, Ohio, in an interview.
“This study was timely because it directly compared long-term outcomes of surgery vs GLP-1 medicines, providing clarity on their relative benefits,” he said.
In the study, published online in Nature Medicine, the researchers compared macrovascular and microvascular outcomes in 1657 adult patients aged 18-75 years with T2D and obesity (defined as a BMI of at least 30) who underwent metabolic surgery (either sleeve gastrectomy or Roux-en-Y gastric bypass) with 2275 similar patients who were treated with GLP-1 RAs.
The primary outcome was all-cause mortality. Secondary outcomes included incident major adverse cardiovascular events (MACEs), nephropathy, and retinopathy over a median 5.9-year follow-up period.
The 10-year cumulative incidence of all-cause mortality was significantly lower in the metabolic surgery group than the GLP-1 RA group (9.0% vs 12.4%; P = .028). Metabolic surgery was also significantly associated with a lower risk for MACEs (adjusted hazard ratio [HR], 0.65; P < .001), nephropathy (adjusted HR, 0.53; P < .001), and retinopathy (adjusted HR, 0.46; P < .002) than with the use of GLP-1 RAs.
“The consistency and magnitude of surgery’s benefits across death, heart, kidney, and eye outcomes were striking,” Aminian said. “While smaller studies suggested such advantages, it was notable that these benefits persisted even in the GLP-1 era.”
Who Benefits Most From Surgery?
The data suggest that metabolic surgery may be especially effective in some subgroups of patients, particularly in patients with a very high BMI (> 45) who require substantial weight loss; individuals with T2D (since GLP-1 medicines are generally less effective in this group); and patients with multiple comorbidities such as cardiovascular, kidney, liver, or other metabolic diseases.
In these patients, positive outcomes “are more difficult to achieve and sustain with medications alone, especially given the common issue of treatment discontinuation,” said Aminian.
The implication for clinical practice is that metabolic surgery should not be reserved as a last resort for obesity and diabetes care, he noted. “Even in the age of GLP-1s, surgery offers durable, life-extending benefits that medications alone often cannot match.”
“Future studies should directly compare bariatric surgery with newer, more potent agents such as semaglutide and tirzepatide, preferably in randomized settings,” Aminian told Medscape Medical News.
Additional research to identify reliable predictors of response is needed as well to determine which patients would benefit most from different therapies, he said.
Numerous Factors Affect Choice of Therapy
“These data support the current body of evidence that has shown that the magnitude of the effect of surgery exceeds that of medical therapy,” said Andrew Kraftson, MD, specialist in endocrinology and internal medicine at the University of Michigan, Ann Arbor, Michigan, in an interview.
Based on mechanistic and outcomes studies, bariatric surgery is more than “weight-loss surgery” but is, in fact, “metabolic surgery,” with hormonal and cardiopulmonary benefits, said Kraftson, who was not involved in the study. “Despite the encouraging improvements in pharmacology therapy for both diabetes and weight, the overall effect of surgery remains stronger on average,” he noted.
But deciding between therapies is not simple, and each patient and clinician must consider numerous medical factors. “These include surgical and medication risks, mental health status, eating patterns, gastrointestinal issues, and diabetes complications,” Kraftson told Medscape Medical News. Nonmedical factors, including financial and social circumstances, must also be considered, but patient preference is the ultimate deciding factor.
As the researchers acknowledged, a key limitation of the study was that semaglutide was not available until late in the study period (2017), and tirzepatide was not available until the end of the study (2022), said Kraftson. “Consequently, the use and effect of these highly effective treatments were not well represented.” The study also included a growing proportion of post-bariatric surgery patients who are on GLP-1-based therapies for reasons not specifically described in the study, he noted.
Kraftson agreed with the researchers that longer-term studies are needed to study the effect of these more potent GLP-1-based therapies. “Studies are also needed to assess the effect of the combination of both surgery and GLP-1-based therapies,” he said.
Reductions in Costs as Well as Weight
Another study published online in JAMA Surgery compared not only weight loss but also ongoing costs of metabolic surgery and GLP-1s for adults with obesity.
Tyson S. Barrett, PhD, of Highmark Health, Pittsburgh, and colleagues looked at data from approximately 30,000 individuals — 14,101 of whom underwent metabolic bariatric surgery, and 16,357 of whom received GLP-1 RAs. Baseline characteristics were similar between the groups.
The primary outcomes of the study were weight loss and ongoing monthly costs over 2 years after the initial treatment (surgery or the start of medication). Over 2 years, the mean total costs were significantly higher for patients treated with GLP-1 RAs than those who underwent surgery ($63,483 vs $51,794; P < .001).
Higher pharmacy costs for the GLP-1 RA group were the main source of the difference in costs, the researchers noted.
Total weight loss was significantly greater at 2 years in the surgery group than in the medication group (28.3% vs 10.3%; P < .001), based on 1291 patients who underwent surgery and 257 patients treated with medication.
The researchers also found fewer obesity-related comorbidities and lower healthcare utilization after 2 years among surgery patients compared with medication patients. This suggests that the lifetime costs of comorbidity treatment and healthcare use may be lower following metabolic surgery than with ongoing weight management using GLP-1 RAs, they stated.
However, the study findings were limited by the variable follow-up time frame, the use of different databases for clinical and economic information, and lack of data on the use of GLP-1 RAs as adjuvant therapy before or in addition to surgery, the researchers wrote.
Further Comparison Unwarranted
The JAMA Surgery study results and conclusions come as no surprise, as individuals who undergo bariatric surgery can expect to lose approximately 30% of their total weight, while most patients’ weight loss on medication is more modest, wrote Rhami Khorfan, MD, of Loma Linda University School of Medicine, Loma Linda, California, and Anne P. Ehlers, MD, of the University of Michigan, in an invited commentary accompanying the study.
“Given this knowledge, it seems that further comparison of GLP-1 RAs vs MBS [metabolic bariatric surgery] for weight-loss outcomes is unwarranted,” the editorialists wrote.
The study by Aminian and colleagues reported receiving no outside funding. Aminian disclosed receiving research grants from Medtronic and Ethicon, and serving as a consultant for Medtronic, Ethicon, and Eli Lilly and Company.
The study by Barrett and colleagues reported receiving funding from Medtronic for consulting and medical writing services. Barrett disclosed having no financial conflicts of interest.
Ehlers disclosed receiving grant funding from the National Institute of Diabetes and Digestive and Kidney Diseases.
Kraftson disclosed having no financial conflicts of interest.