Kidney and Survival Benefits of Semaglutide in Diabetes With Chronic Kidney Disease
Key result
Semaglutide provides kidney and survival benefits in patients with T2D and CKD.
- n=3,533
Why the study?
Cardiovascular disease increases risks of CKD progression and mortality in type 2 diabetes, and the effects of semaglutide on kidney and survival outcomes by baseline cardiovascular status were assessed in the FLOW trial.
Does semaglutide improve kidney and survival outcomes in patients with type 2 diabetes and chronic kidney disease across different baseline cardiovascular risk profiles?
Key Points
- To assess the effects of semaglutide on major kidney and survival outcomes stratified by baseline cardiovascular disease status in individuals with type 2 diabetes and chronic kidney disease.
- Secondary analysis of the randomized FLOW trial (NCT03819153) evaluating once-weekly semaglutide versus placebo in patients with type 2 diabetes and chronic kidney disease.
- Stratified participants by baseline status: atherosclerotic cardiovascular disease (ASCVD; 1,198 of 3,533), heart failure (678 of 3,532), and high total cardiovascular disease risk among those without established cardiovascular disease (1,329 of 2,000).
- Evaluated primary composite kidney outcomes (dialysis, kidney transplantation, kidney death, or cardiovascular death) and confirmatory secondary all-cause mortality.
- Semaglutide reduced the primary composite kidney outcome in patients with ASCVD (119 of 593 vs 146 of 605; HR: 0.80; 95% CI: 0.63–1.02) and without ASCVD (212 of 1,174 vs 264 of 1,161; HR: 0.74; 95% CI: 0.62–0.89; P for interaction = 0.62), as well as with heart failure (67 of 342 vs 88 of 336; HR: 0.67; 95% CI: 0.49–0.93) and without heart failure (264 of 1,424 vs 322 of 1,430; HR: 0.79; 95% CI: 0.67–0.93; P for interaction = 0.40).
- Kidney outcomes improved similarly in groups with high cardiovascular risk (134 of 675 vs 168 of 654; HR: 0.73; 95% CI: 0.58–0.91) and without high risk (44 of 331 vs 58 of 340; HR: 0.73; 95% CI: 0.49–1.08; P for interaction = 0.99), with 3-year numbers needed to treat of 22, 13, and 17 for ASCVD, heart failure, and PREVENT score ≥20%, respectively.
- All-cause mortality was reduced across ASCVD groups (with ASCVD: 99 of 593 vs 121 of 605, HR: 0.82, 95% CI: 0.63–1.07; without ASCVD: 128 of 1,174 vs 158 of 1,161, HR: 0.78, 95% CI: 0.62–0.99; P for interaction = 0.79) and heart failure groups (with: HR: 0.75; 95% CI: 0.54–1.05; without: HR: 0.81; 95% CI: 0.66–0.99; P for interaction = 0.74).
Study Design
Type
RCT (n=3,533)
Structured PICO
Does semaglutide improve kidney and survival outcomes in patients with type 2 diabetes and chronic kidney disease across different baseline cardiovascular risk profiles?
P
Population
3,533 participants with type 2 diabetes and chronic kidney disease, evaluated for kidney and survival outcomes by baseline cardiovascular status over 3 years.
I
Intervention
Semaglutide once weekly
O
Outcome
Composite of dialysis, transplantation, and kidney or cardiovascular deathcomposite
Semaglutide provides consistent kidney and survival benefits in patients with type 2 diabetes and chronic kidney disease, regardless of their baseline cardiovascular disease status or risk.
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“a key opportunity to intensify CV-kidney therapies in real-world practice in high-risk CKD even without overt CVD being present, given comparable event rates and benefits from therapies.”
“the biggest win yet of a completed trial for kidney disease”
PGPranav GarimellaChief Medical Officer, American Kidney Fund
“It isn't just kidney failure progression that was stopped; it was cardiovascular disease events, which are the number 1 cause of death in these patients. And so actually, being able to slow both kidney disease and cardiovascular disease is, I think, a critical advancement in helping take care of this patient population.”
Implication
May support semaglutide use in T2D with CKD; leaves open confirmation from dedicated prospective trials.
Abstract
BACKGROUND: Cardiovascular disease increases risks of chronic kidney disease (CKD) progression and mortality in type 2 diabetes. OBJECTIVES: The study sought to assess semaglutide effects on kidney and survival outcomes by baseline cardiovascular status in the FLOW trial. All-cause death was a confirmatory secondary outcome. RESULTS: At baseline, 1,198 (33.9%) of 3,533, 678 (19.2%) of 3,532, and 1,329 (66.5%) of 2,000 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 of 593 vs 146 of 605) or without (212 of 1,174 vs 264 of 1,161) ASCVD (HR: 0.80; 95% CI: 0.63-1.02; and HR: 0.74; 95% CI: 0.62-0.89, respectively; P for interaction = 0.62), with (67 of 342 vs 88 of 336) or without (264 of 1,424 vs 322 of 1,430) heart failure (HR: 0.67; 95% CI: 0.49-0.93; and HR: 0.79; 95% CI: 0.67-0.93, respectively; P for interaction = 0.40), and with (134 of 675 vs 168 of 654) or without (44 of 331 vs 58 of 340) high total cardiovascular disease risk (HR: 0.73; 95% CI: 0.58-0.91; and HR: 0.73; 95% CI: 0.49-1.08, respectively; P for interaction = 0.99). Numbers needed to treat to prevent 1 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 of 593 vs 121 of 605) or without (128 of 1,174 vs 158 of 1,161) ASCVD (HR: 0.82; 95% CI: 0.63-1.07; and HR: 0.78; 95% CI: 0.62-0.99, respectively; P for interaction = 0.79), with (64 of 342 vs 79 of 336) or without (163 of 1,424 vs 200 of 1,430) heart failure (HR: 0.75; 95% CI: 0.54-1.05; and HR: 0.81; 95% CI: 0.66-0.99, respectively; P for interaction = 0.74), and with (73 of 675 vs 98 of 654) or without (23 of 331 vs 28 of 340) high total cardiovascular disease risk (HR: 0.71; 95% CI: 0.52-0.95; and HR: 0.82; 95% CI: 0.47-1.43, respectively; P for 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. (Evaluate Renal Function with Semaglutide Once Weekly [FLOW]; NCT03819153).
Coverage & sources
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Cite This Study
Tuttle et al. (2026) conducted an RCT in Type 2 diabetes with chronic kidney disease (n=3,533). Semaglutide was evaluated on Dialysis, transplantation, and kidney or cardiovascular death. Semaglutide reduced kidney and survival outcomes in type 2 diabetes with CKD, regardless of baseline ASCVD or heart failure.