Gasoyan Hamlet, Alavi Mohammad Hesam, Zajichek Alexander, Casacchia Nicholas J, Al Jabri Abdullah, Bena James, Feng Xiaoxi, Wilson Rickesha, Corcelles Ricard, Butsch W Scott, Singh Rishi P, Das Nikhil, Jeong Hejin, Mentias Amgad, Tang W H Wilson, Burguera Bartolome, Rosenthal Raul J, Nissen Steven E, Rothberg Michael B, Aminian Ali
Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, OH, USA.
Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA.
Nat Med. 2025 Sep 16. doi: 10.1038/s41591-025-03893-3.
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.
代谢手术和胰高血糖素样肽-1（GLP-1）受体激动剂（RA）均可改善心脏代谢结局，但二者的长期结局尚未得到直接比较。在此，我们比较了1657例2型糖尿病合并肥胖且接受代谢手术的患者（女性占65.7%）与2275例接受GLP-1 RA治疗的类似患者（女性占53.5%）的大血管和微血管结局。我们采用双重稳健估计方法平衡组间基线特征，在中位随访5.9年期间，研究全因死亡率、首次发生的主要不良心血管事件（MACE）、肾病和视网膜病变的发生时间。代谢手术组全因死亡率的10年累积发生率为9.0%（95%置信区间（CI）6.8 - 10.8%），GLP-1 RA组为12.4%（95% CI 9.9 - 15.2%）（调整后风险比（HR）0.68（95% CI 0.48 - 0.96），P = 0.028）。与GLP-1 RA组相比，代谢手术还与较低的MACE风险（调整后HR 0.65；95% CI 0.51 - 0.82；P < 0.001）、肾病风险（调整后HR 0.53；95% CI 0.43 - 0.67；P < 0.001）和视网膜病变风险（调整后HR 0.46；95% CI 0.29 - 0.75；P = 0.002）相关。这些发现表明，即使有GLP-1 RA可用，代谢手术仍优于药物治疗。未来的研究应比较代谢手术与对体重减轻更有效的新型GLP-1 RA的心脏代谢结局。
