Better Outcomes and Lower Cost with Bariatric Surgery Over GLP-1s

Metabolic bariatric surgery is associated with a lower risk of major adverse cardiovascular events, as well as a lower risk of all-cause mortality, nephropathy, and retinopathy, when compared with pharmacotherapy in people with type 2 diabetes and obesity, according to results of a new observational study.

At 10 years, the cumulative incidence of MACE was 23.7% among those who underwent bariatric surgery compared with 34.0% in those treated with glucagon-like peptide-1 (GLP-1) receptor agonists, which mostly included older weight-loss drugs like liraglutide (Saxenda; Novo Nordisk) and dulaglutide (Trulicity; Eli Lilly), report investigators in a paper published this week in Nature Medicine.

In an adjusted model, the absolute risk difference in MACE favoring bariatric surgery was 8.8%, with a 3.8% lower absolute risk of all-cause mortality.   

“Many people have suggested that with the introduction of the new GLP-1s, they may replace surgery or that surgery may not have a role in the future,” senior investigator Ali Aminian, MD (Cleveland Clinic, OH), told TCTMD. “This study showed that even in the GLP-1 era, surgery can still provide some additional benefit, including a reduction in mortality, which is extremely important.”

A second study of more than 30,000 patients with obesity, published online this week in JAMA Surgery, showed that bariatric metabolic surgery was associated with greater weight loss and lower long-term costs to the healthcare system than treatment with a GLP-1 receptor agonist.  

The senior author of that paper, George Eid, MD (Allegheny Health Network, Pittsburgh, PA), stressed that their analysis is not intended to prove superiority of one weight-loss approach over the other since they are both effective. “The question is who would benefit from what—that’s what it comes down to because we need to scale up,” he stressed to TCTMD, adding that half of the US population is predicted to have a body mass index (BMI) of at least 30 kg/m² by 2030.

Even in the GLP-1 era, surgery can still provide some additional benefit, including a reduction in mortality, which is extremely important. Ali Aminian

Getting a Handle on Clinical Events

Metabolic bariatric surgery has an established track record with extensive follow-up showing durable weight loss, as well as the remission of type 2 diabetes, hypertension, and dyslipidemia, among other obesity-related diseases. In observational studies and meta-analyses, surgery has consistently shown to be associated with a lower risk of cardiovascular disease when compared with nonsurgical interventions or usual care.

The GLP-1 receptor agonist semaglutide (Wegovy; Novo Nordisk) also has proven cardiovascular benefit. In SELECT, semaglutide reduced the risk of a composite endpoint of CV death, nonfatal MI, and nonfatal stroke in patients with obesity and a prior history of cardiovascular disease. Tirzepatide (Zepbound; Eli Lilly), a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist, is currently being tested in SURMOUNT-MMO, a large cardiovascular outcomes trial, and results are expected in 2027.

No data comparing the two weight-loss approaches in a randomized controlled trial are yet available. There are some studies comparing surgery and drug therapy for weight loss, with bariatric surgery outperforming the medications. The issue, said Aminian, is that many patients treated with medical therapy often stop their treatment after a relatively short period of time. As a result, these real-world analyses show dramatic differences in weight loss between the two methods.

The question is who would benefit from what—that’s what it comes down to because we need to scale up. George Eid

The first study by Aminian and colleagues, including first author Hamlet Gasoyan, PhD (Cleveland Clinic), looked at clinical outcomes of 3,932 patients (mean age 54.2 years; 58.7% female) with type 2 diabetes and obesity treated at the Cleveland Clinic between 2010 and 2017. Of these, 1,657 underwent metabolic surgery with gastric bypass or sleeve gastrectomy and 2,275 were treated with GLP-1s, including liraglutide (65.4%), dulaglutide (48.6%), exenatide (32.5%), semaglutide (26.5%), tirzepatide (4.4%), and lixisenatide (2.9%). Median follow-up in the entire cohort was 5.9 years.

The cumulative 10-year incidence of all-cause mortality was significantly higher in those treated with GLP-1s: 12.4% vs 9.0% in the surgical arm (fully adjusted HR 0.68; 95% CI 0.48-0.96). In addition to the 35% lower relative risk in MACE with surgery at 10 years (HR 0.65; 95% CI 0.51-0.82), the procedure was associated with a 47% lower relative risk of nephropathy and a 54% lower relative risk of retinopathy compared with the medications.

With MACE, the event curves began to separate in favor of bariatric surgery by 1 year, whereas the difference in all-cause mortality was not evident until 4 years. Aminian noted that in the early days and weeks after surgery, event rates are slightly higher with surgery given the up-front risks of a more invasive procedure. Risks of nephropathy are also higher early, which is common given that some patients will be dehydrated after surgery due to food intolerance and/or nausea.

“But after 2 years, the metabolic improvements kick in and protect the kidney” and there is a very large separation of the nephropathy event curves, he said.

With the second study, Eid’s team, with lead author Tyson Barrett, PhD (Allegheny Health Network), studied insurance claims data linked to electronic health records collected between 2018 and 2023. Among the 30,458 patients (mean age 50 years; 66.1% female), use of GLP-1s included mostly semaglutide (45%), dulaglutide (25%), liraglutide (17%), and tirzepatide (11%).

Surgery resulted in a mean 28.3% reduction in body weight from baseline compared with a 10.3% reduction with medical therapy (P < 0.001). The mean total costs over 2 years were $63,483 for treatment with a GLP-1 and $51,794 for bariatric surgery (P < 0.001). While medical costs were higher with surgery, higher pharmacy costs in the GLP-1 receptor agonist group drove the total 2-year difference in costs.

“If we really dig into it, [surgery] was more cost-effective because we had 37% less ER visits, 21% less inpatient admissions, and we also had less outpatient admissions,” said Eid.

He told TCTMD one of the strengths of the study is that it included a subset of patients treated at the Allegheny Health Network, which allowed the researchers to get a better understanding of the clinic data and associated costs.

Some Limitations

One of the main limitations of the observational study suggesting better clinical outcomes with metabolic bariatric surgery is that many patients were treated with older-generation GLP-1 receptor agonists. “To be eligible for the study, they needed to be on the study drug for some time,” said Aminian, noting these older drugs aren’t as effective as semaglutide and tirzepatide for weight loss. “Those are good medications for diabetes, but not very good medications for obesity.”

Mark Herman, MD (Baylor College of Medicine, Houston, TX), who commented on this study for TCTMD, said there are limited comparative outcomes data in the field, with this being likely the “largest and most comprehensive head-to-head comparison to date.” Metabolic surgery has “dramatic benefits on mortality and cardiovascular endpoints, and there is growing literature that GLP-1 receptor agonists do so as well,” he added.

While these new data are welcome, there are limitations to what can be gleaned from them. “The major issue is that this study started in 2010,” Herman said. “The majority of GLP-1 receptor agonists that were utilized were not the current, more potent GLP-1 receptor agonists.” The weight loss achieved with semaglutide and liraglutide is larger than with the older agents, and semaglutide has been proven in SELECT to reduce MACE, he said.

While a randomized controlled trial would be a great addition in this space, it would be limited by how fast the field is changing. “By the time a well-organized, large study is conducted and published, the findings are out of date or maybe not applicable anymore,” Herman said. Such a trial would also be very costly, and it’s uncertain who would be interested in paying for it, he continued.

Aminian said the introduction of GLP-1s has been a boon for patients and he is pleased they are available. Some patients don’t want to undergo surgery, while others might not wish to take medication for the rest of their life.

“Choice should be available for patients,” said Aminian. Some patients will stand to benefit more from surgery given the larger reductions in weight, he added. For example, a patient with class 3 obesity (BMI > 40 kg/m²) might lose 20% of their body weight if they stay on the medication but would still be considered obese given their high starting weight. Plus, adherence remains a major issue. On the other hand, a patient with class 1 obesity (BMI 30.0 to 34.9 kg/m²) could try medications.  

He noted that weight-loss pharmacotherapy may get stronger in the future and approach surgical results.

For Herman, what’s really needed right now are studies looking into which patients benefit the most from the different weight-loss options. Eid agreed, noting that patient selection is critical, just as it would be for physicians trying to decide between CABG surgery and PCI for patients with coronary artery disease.