In a groundbreaking new study published in Nature Medicine, researchers from Cleveland Clinic have revealed compelling evidence that metabolic surgery significantly improves long-term health outcomes for individuals living with obesity and type 2 diabetes compared to treatment with GLP-1 receptor agonist medications alone. This large-scale observational study underscores the profound and enduring benefits of bariatric surgery, emphasizing its role not only in weight loss but also in reducing mortality and serious cardiovascular and microvascular complications over a decade-long follow-up period.
The study, known as the M6 study—an acronym for Macrovascular and Microvascular Morbidity and Mortality after Metabolic Surgery versus Medicines—tracked nearly 4,000 adults who were treated at Cleveland Clinic. Of these participants, 1,657 underwent metabolic surgery procedures, such as gastric bypass or sleeve gastrectomy, while the remaining 2,275 patients were managed with GLP-1 receptor agonists, a class of drugs that includes liraglutide, dulaglutide, exenatide, semaglutide, and tirzepatide. The longitudinal nature of the study provided an unprecedented view into the comparative effectiveness of these two therapeutic strategies across a full decade of patient outcomes.
One of the most striking findings of the study is the substantial reduction in mortality associated with metabolic surgery. Patients who underwent surgery exhibited a 32% lower risk of death compared to those treated exclusively with medical therapy. This survival advantage highlights surgery’s potential to transform chronic disease management by fundamentally altering the trajectory of obesity and type 2 diabetes, diseases that are known for their progressive nature and devastating complications.
Beyond survival benefits, the research team observed notable declines in major cardiovascular events among surgical patients. Specifically, the risk of heart attacks, heart failure, and stroke was reduced by 35% in those who had metabolic surgery versus those on GLP-1 medicines. Given that cardiovascular disease is the leading cause of death in individuals with diabetes, these findings carry profound implications for clinical practice and patient counseling, suggesting that surgical intervention should be strongly considered for eligible patients to mitigate these risks.
Kidney health also benefited markedly following surgery. The incidence of serious kidney disease dropped by nearly half—47%—among surgical patients. Chronic kidney disease (CKD) commonly complicates diabetes and obesity, contributing substantially to morbidity and healthcare costs. By lowering the burden of CKD, metabolic surgery offers a path to preserving renal function and preventing progression to kidney failure, which often necessitates dialysis or transplantation.
Additionally, the study highlighted a remarkable 54% reduction in diabetes-related retinopathy, a serious microvascular complication that can result in vision loss. The mechanisms by which metabolic surgery achieves such protective effects against retinal damage likely extend beyond mere glucose control, involving improvements in systemic inflammation, oxidative stress, and vascular function, though further research is necessary to elucidate these pathways fully.
From a metabolic standpoint, patients receiving surgery lost an average of 21.6% of their initial body weight over a ten-year span, a figure that far surpasses the 6.8% weight reduction achieved through GLP-1 receptor agonist therapy alone. Correspondingly, hemoglobin A1c—a clinical marker reflecting average blood glucose levels—improved more substantially in the surgery group (-0.86%) than in the medication group (-0.23%). These differences in glycemic control likely underpin much of the divergence in long-term health outcomes observed.
Moreover, those who underwent metabolic surgery required fewer medication prescriptions to manage diabetes, hypertension, and hyperlipidemia across the long term. This indicates that surgery may not only improve patients’ physiological profiles but also reduce the pharmacological burden and associated side effects. It could ultimately translate into lower healthcare costs and better quality of life for these individuals.
Despite these powerful findings, the researchers caution that the study’s observational design means causality cannot be definitively established. Unlike randomized controlled trials, this real-world examination relied on clinical data collected over time without the random assignment of treatment modalities. Additionally, the study did not focus exclusively on the newest GLP-1 receptor agonists, which have demonstrated enhanced efficacy, leaving open the question of how metabolic surgery compares to these emerging therapies.
Dr. Ali Aminian, director of Cleveland Clinic’s Bariatric & Metabolic Institute and the study’s primary investigator, emphasized that “even with today’s best medicines, metabolic surgery offers unique and lasting benefits for people with obesity and diabetes.” He pointed out that the surgery’s effects extend far beyond simple weight reduction, encompassing cardiovascular protection, kidney function preservation, and prevention of eye complications. These multifaceted benefits reflect the complex interplay of metabolic and hormonal changes initiated by surgical interventions.
Senior author Dr. Steven Nissen, Chief Academic Officer of the Heart, Vascular & Thoracic Institute at Cleveland Clinic, remarked on the “survival advantage” provided by surgery despite the advent of powerful new diabetes medications. He stressed the importance of maintaining metabolic surgery as a cornerstone treatment option for eligible patients, particularly given the durability of its effects compared to pharmacological treatments that some patients may discontinue over time.
The study’s implications ripple across clinical and public health spheres. As obesity and type 2 diabetes continue their global rise, seemingly inexorable, identifying treatment strategies that not only manage symptoms but also extend life and reduce serious complications is paramount. Metabolic surgery, once viewed primarily as a weight-loss aid, is increasingly recognized for its profound systemic benefits and potential to alter the natural history of diabetes.
Moving forward, the authors recommend that future investigations directly compare metabolic surgery with new-generation GLP-1 therapies, such as semaglutide and tirzepatide, through randomized controlled trials. Such research will be vital in refining treatment algorithms and personalizing therapy, ensuring patients receive the most effective, evidence-based care tailored to their individual clinical profile and preferences.
This landmark Cleveland Clinic study elevates the conversation around obesity and diabetes treatment, illuminating how surgical intervention is not just about altering body size but is a potent tool in reducing mortality and safeguarding vital organ systems from the ravages of chronic disease. It challenges clinicians to consider surgery earlier in the therapeutic timeline and patients to view it as a compelling option for long-term health optimization.
Subject of Research: Comparison of long-term macrovascular and microvascular outcomes in patients with obesity and type 2 diabetes treated with metabolic (bariatric) surgery versus GLP-1 receptor agonist medications.
Article Title: Macrovascular and microvascular outcomes of metabolic surgery versus GLP-1 receptor agonists in patients with diabetes and obesity
News Publication Date: 16-Sep-2025
Web References:
Nature Medicine Article
DOI: 10.1038/s41591-025-03893-3
Keywords: Metabolic disorders; Obesity; Type 2 diabetes; Metabolic/bariatric surgery; GLP-1 receptor agonists; Cardiovascular disease; Kidney disease; Diabetic retinopathy; Weight loss; Glycemic control; Long-term outcomes; Diabetes complications
Tags: bariatric surgery benefitscardiovascular complications bariatric surgeryCleveland Clinic research studygastric bypass outcomesGLP-1 medications comparisonlong-term health outcomes obesityM6 study findingsmetabolic surgery effectivenessmortality reduction obesity treatmentobservational study on obesity treatmentsleeve gastrectomy advantagestype 2 diabetes treatment options
