Background: Cardiovascular disease increases risks of chronic kidney disease (CKD) progression and mortality in type 2 diabetes.
Objectives: Assess semaglutide effects on kidney and survival outcomes by baseline cardiovascular status in the FLOW trial.
Methods: Participants with type 2 diabetes and CKD were randomized to once-weekly subcutaneous semaglutide 1.0 mg versus placebo. Baseline subgroups included atherosclerotic cardiovascular disease (ASCVD), heart failure, and high total cardiovascular disease risk without established cardiovascular disease (10-year PREVENT score ≥20%). Primary outcome: ≥50% estimated glomerular filtration rate (eGFR) decline, eGFR <15 mL/min/1.73 m2, dialysis, transplant, and kidney or cardiovascular death. All-cause death was a confirmatory secondary outcome.
Results: At baseline, 1,198/3,533 (33.9%), 678/3,532 (19.2%), and 1,329/2,000 (66.5%) participants had ASCVD, heart failure, or high total cardiovascular disease risk in those without established cardiovascular disease, respectively. Semaglutide reduced the primary outcome risk in subgroups with (119/593 versus 146/605) or without (212/1,174 versus 264/1,161) ASCVD (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.63-1.02; HR: 0.74, 95% CI: 0.62-0.89; P-interaction=0.62), with (67/342 versus 88/336) or without (264/1,424 versus 322/1,430) heart failure (HR: 0.67, 95% CI: 0.49-0.93; HR: 0.79, 95% CI: 0.67-0.93; P-interaction=0.40), and with (134/675 versus 168/654) or without (44/331 versus 58/340) high total cardiovascular disease risk (HR: 0.73, 95% CI: 0.58-0.91; HR: 0.73, 95% CI: 0.49-1.08; P-interaction=0.99). Numbers-needed-to-treat to prevent one primary kidney outcome at 3 years were 22, 13, and 17 in the ASCVD, heart failure, and PREVENT score ≥20% subgroups, respectively. Semaglutide also reduced risks of all-cause death with (99/593 versus 121/605) or without (128/1,174 versus 158/1,161) ASCVD (HR: 0.82, 95% CI: 0.63-1.07; HR: 0.78, 95% CI: 0.62-0.99; P-interaction=0.79), with (64/342 versus 79/336) or without (163/1,424 versus 200/1,430) heart failure (HR: 0.75, 95% CI: 0.54-1.05; HR: 0.81, 95% CI: 0.66-0.99; P-interaction=0.74), and with (73/675 versus 98/654) or without (23/331 versus 28/340) high total cardiovascular disease risk (HR: 0.71, 95% CI: 0.52-0.95; HR: 0.82, 95% CI: 0.47-1.43; P-interaction=0.63).
Conclusions: Semaglutide improved kidney and survival outcomes in type 2 diabetes with CKD, irrespective of established ASCVD, heart failure, or high total cardiovascular disease risk.
Editors
Editor-in-Chief
Harlan M. Krumholz, MD, SM, FACC
CME Editor
Ragavendra R. Baliga, MD
Author
Katherine R. Tuttle, MD
Important Dates
Date of Release: June 2, 2026
Term of Approval/Date of CME/MOC Expiration: June 1, 2027