Macrovascular and microvascular outcomes of metabolic surgery versus GLP-1 receptor agonists in patients with diabetes and obesity.

Both metabolic surgery and glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) improve cardiometabolic outcomes, but their long-term outcomes have not been directly compared. Here, we compared macrovascular and microvascular outcomes in 1,657 patients (65.7% female) with type 2 diabetes and obesity who underwent metabolic surgery with 2,275 similar patients (53.5% female) who received treatment with GLP-1 RAs. Using a doubly robust estimation method to balance baseline characteristics between groups, we examined the time to all-cause mortality, incident major adverse cardiovascular events (MACE), nephropathy and retinopathy over a median follow-up of 5.9 years. The 10-year cumulative incidence of all-cause mortality was 9.0% (95% confidence interval (CI) 6.8-10.8%) in the metabolic surgery group and 12.4% (95% CI 9.9-15.2%) in the GLP-1 RA group (adjusted hazard ratio (HR) 0.68 (95% CI 0.48-0.96), P = 0.028). Compared with the GLP-1 RA group, metabolic surgery was also associated with a lower risk of MACE (adjusted HR 0.65; 95% CI 0.51-0.82; P < 0.001), nephropathy (adjusted HR 0.53; 95% CI 0.43-0.67; P < 0.001) and retinopathy (adjusted HR 0.46; 95% CI 0.29-0.75; P = 0.002). These findings indicate that even with the availability of GLP-1 RAs, metabolic surgery remains superior to medical treatment. Future studies should compare the cardiometabolic outcomes of metabolic surgery with newer GLP-1 RAs that are more effective for weight reduction.