Surgery reduces the risks of death, heart disease, kidney failure, and eye damage more effectively than GLP-1 medicines.
A major study conducted at Cleveland Clinic found that individuals with obesity and type 2 diabetes who underwent weight-loss surgery lived longer and experienced fewer serious complications compared with those treated only with GLP-1 receptor agonist drugs.
Over a 10-year period, patients who had bariatric or metabolic surgery lost more weight, managed their blood sugar more effectively, and required fewer medications for diabetes and heart disease. The findings were published in Nature Medicine.
“Even with today’s best medicines, metabolic surgery offers unique and lasting benefits for people with obesity and diabetes,” said Ali Aminian, M.D., director of Cleveland Clinic’s Bariatric & Metabolic Institute and primary investigator of the study. “The benefits we observed went beyond weight loss. Surgery was linked to fewer heart problems, less kidney disease, and even lower rates of diabetes-related eye damage.”
GLP-1 (glucagon-like peptide-1) receptor agonists are a group of drugs commonly prescribed for type 2 diabetes and obesity, known to lower health risks. Both surgery and GLP-1 treatments improve metabolism and cardiovascular outcomes.
Details of the M6 study
The M6 study (Macrovascular and Microvascular Morbidity and Mortality after Metabolic Surgery versus Medicines) tracked 3,932 adults with diabetes and obesity treated at Cleveland Clinic for up to a decade. Of these, 1,657 underwent metabolic surgery such as gastric bypass or sleeve gastrectomy, while 2,275 received GLP-1 medicines, including liraglutide, dulaglutide, exenatide, semaglutide, and tirzepatide.
At the end of the study, patients who had metabolic surgery had a:
- A 32% reduction in the risk of death
- A 35% reduction in the risk of major cardiovascular events (including heart attack, heart failure, or stroke)
- A 47% reduction in the likelihood of developing severe kidney disease
- A 54% reduction in the risk of diabetes-related eye damage (retinopathy)
On average, people who had metabolic surgery lost 21.6% of their body weight over 10 years, compared with 6.8% weight loss in people who took GLP-1 medicines. Hemoglobin A1c, a marker of average blood sugar, improved more with surgery (-0.86%) than with GLP-1 medicines (-0.23%). Patients in the surgery group also required fewer prescriptions for diabetes, blood pressure, and cholesterol.
Implications for treatment choices
“Even in the era of these powerful new drugs to treat obesity and diabetes, metabolic surgery may provide additional benefits, including a survival advantage,” said Steven Nissen, M.D., Chief Academic Officer of the Heart, Vascular & Thoracic Institute at Cleveland Clinic and senior author of the study.
“Our findings indicate that surgery should remain an important treatment option for obesity and diabetes,” said Dr. Aminian. “These long-term benefits are harder to achieve with GLP-1 medicines alone, as many patients stop using the medications over time.”
According to the authors, the study has some limitations. It was observational rather than a randomized comparison of drugs and surgery, and it did not focus exclusively on the newest and most effective GLP-1 medicines. The researchers note that future studies should directly compare surgery with newer GLP-1 therapies, such as semaglutide and tirzepatide, to further guide treatment decisions.
Reference: “Macrovascular and microvascular outcomes of metabolic surgery versus GLP-1 receptor agonists in patients with diabetes and obesity” by Hamlet Gasoyan, Mohammad Hesam Alavi, Alexander Zajichek, Nicholas J. Casacchia, Abdullah Al Jabri, James Bena, Xiaoxi Feng, Rickesha Wilson, Ricard Corcelles, W. Scott Butsch, Rishi P. Singh, Nikhil Das, Hejin Jeong, Amgad Mentias, W. H. Wilson Tang, Bartolome Burguera, Raul J. Rosenthal, Steven E. Nissen, Michael B. Rothberg and Ali Aminian, 16 September 2025, Nature Medicine.
DOI: 10.1038/s41591-025-03893-3
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