Bariatric Surgery vs. GLP-1 Medications: What Cleveland Clinic’s M6 Study Means for Long-Term Health

TL;DR: Cleveland Clinic’s new M6 study on bariatric surgery vs glp-1’s—published in Nature Medicine on September 16, 2025—found that, in people with obesity and type 2 diabetes, metabolic (bariatric) surgery was associated with better long-term survival and fewer heart, kidney, and eye complications than GLP-1 medications alone. Average 10-year weight loss was ~21.6% after surgery vs 6.8% with GLP-1 therapy alone. Cleveland Clinic

What is the M6 Study?

The M6 (Macrovascular & Microvascular Morbidity and Mortality) study followed 3,932 adults with obesity and type 2 diabetes treated at Cleveland Clinic for up to 10 years: 1,657 had metabolic surgery (sleeve gastrectomy or gastric bypass) and 2,275 used GLP-1 receptor agonists (e.g., liraglutide, dulaglutide, exenatide, semaglutide, tirzepatide). 

Key outcomes (surgery vs GLP-1 medicines alone)

Compared to medications, surgery offers:

• 32% lower risk of death (all-cause mortality)
• 35% lower risk of major cardiovascular events (heart attack, heart failure, stroke)
• 47% lower risk of serious kidney disease
• 54% lower risk of diabetes-related eye damage (retinopathy)
• Greater average 10-year weight loss: ~21.6% vs ~6.8%
• Bigger A1c reduction: −0.86% vs −0.23% 

Why Surgery Outperformed GLP-1s in the Real World

Adherence: Whether or not you’re in a study, if you have weight loss surgery, you are left with a permanent tool to help you lose weight and maintain that loss, providing you follow some basic rules. If you are in a study involving medications, however, you are going to be much more likely to stay on the medication than a real-world patient. Studies support this, showing that after a year or two the vast majority of patients on GLP-1’s have stopped the medication due to various reasons such as cost and side effects.

Durability of effect: A large real-world head-to-head analysis presented at ASMBS 2025 found patients lost ~5× more weight at 2 years with sleeve or bypass than with semaglutide/tirzepatide (about 24% vs 4.7–7%), reflecting high discontinuation and adherence challenges with weekly injections.

Metabolic mechanisms: Surgery improves insulin sensitivity, gut hormones, and bile acid signaling—changes that persist even when weight plateaus—helping explain the broader cardiometabolic advantages (heart, kidney, eye) reported in M6.

What This Means If You’re Choosing a Treatment Path

• Both surgery and GLP-1s help with weight and cardiometabolic risk. GLP-1s also show independent benefits in many settings. But this study clearly shows that surgery delivers deeper, more durable benefits. 
• Combination care (e.g., GLP-1s before or after surgery) can be appropriate for some patients—especially to support pre-op risk reduction or post-op plateaus. Work with a bariatric-experienced team.

Who’s a Candidate for Bariatric (Metabolic) Surgery?

According to recently updated guidelines by the ASMBS, you may qualify if you have:

• BMI ≥35, or
• BMI ≥30 with an obesity-related condition (e.g., type 2 diabetes, sleep apnea, hypertension).
  Modern safety profiles for sleeve gastrectomy and gastric bypass are comparable to other common surgeries.

Results You Can Expect at JourneyLite

While individual outcomes vary, long-term studies and real-world data suggest:

• Weight loss: Frequently 20–30%+ total body weight after sleeve or bypass, with the 24% at 2 years figure commonly cited in real-world cohorts. 
• Diabetes control: Higher rates of A1c improvement and medication reduction compared with GLP-1s alone in M6’s 10-year follow-up. 
• Organ protection: Lower 10-year risk of MACE, nephropathy, and retinopathy than GLP-1 therapy alone. 

Bariatric Surgery vs GLP-1 Cost & Coverage Considerations

• Surgery: These procedures are often covered by insurance. Even when they aren’t, the one-time self-pay cost is manageable for many patients.
• GLP-1s: These meds are a significant lifelong ongoing monthly expense; many patients stop due to side effects, supply, or coverage issues.