Semaglutide consistently reduces kidney and mortality risks across cardiovascular subgroups in type 2 diabetes with CKD

Patients with Type 2 Diabetes (T2D) and Chronic Kidney Disease (CKD) face a substantially elevated risk of cardiovascular disease (CVD) progression and mortality. Current standard-of-care often struggles to comprehensively address both kidney and cardiovascular outcomes in this complex population. GLP-1 receptor agonists like semaglutide have demonstrated benefits in T2D and CVD, but their consistent efficacy across various cardiovascular risk profiles within the CKD population needed further clarification to optimize treatment strategies.

The FLOW trial randomized 3,533 participants with Type 2 Diabetes and CKD to receive once-weekly subcutaneous semaglutide 1.0 mg or placebo. Subgroup analyses were performed based on baseline cardiovascular status, including established atherosclerotic cardiovascular disease (ASCVD), heart failure, or high total cardiovascular disease risk (PREVENT score ≥20%) without established CVD. The primary endpoint was a composite of major kidney events (≥50% eGFR decline, eGFR <15 mL/min/1.73 m2, dialysis, transplantation) and kidney or cardiovascular death. All-cause death was a confirmatory secondary outcome.

Semaglutide consistently reduced the risk of the primary composite kidney and cardiovascular outcome across all predefined cardiovascular subgroups. In participants with ASCVD, semaglutide reduced the primary outcome risk (HR: 0.80; 95% CI: 0.63-1.02), and similarly in those without ASCVD (HR: 0.74; 95% CI: 0.62-0.89), with a P for interaction = 0.62. For heart failure patients, the HR was 0.67 (95% CI: 0.49-0.93), and without heart failure, it was 0.79 (95% CI: 0.67-0.93), showing no significant interaction (P for interaction = 0.40). Patients with high total CVD risk saw an HR of 0.73 (95% CI: 0.58-0.91), consistent with those without (P for interaction = 0.99).

The numbers needed to treat (NNT) to prevent 1 primary kidney outcome at 3 years were 22 in the ASCVD subgroup, 13 in the heart failure subgroup, and 17 in the high PREVENT score ≥20% subgroup. Semaglutide also reduced risks of all-cause death across these subgroups.