Semaglutide improved kidney and survival outcomes in type 2 diabetes with CKD, irrespective of established ASCVD, heart failure, or high total cardiovascular disease risk.
Key Findings
Results
Semaglutide reduced the primary kidney outcome risk consistently regardless of atherosclerotic cardiovascular disease (ASCVD) status at baseline.
In participants with ASCVD: 119 of 593 (semaglutide) vs 146 of 605 (placebo), HR: 0.80; 95% CI: 0.63-1.02
In participants without ASCVD: 212 of 1,174 (semaglutide) vs 264 of 1,161 (placebo), HR: 0.74; 95% CI: 0.62-0.89
P for interaction = 0.62, indicating no statistically significant difference in treatment effect between subgroups
At baseline, 1,198 of 3,533 participants (33.9%) had established ASCVD
Number needed to treat to prevent 1 primary kidney outcome at 3 years was 22 in the ASCVD subgroup
Results
Semaglutide reduced the primary kidney outcome risk in participants with and without heart failure, with no significant interaction between treatment effect and heart failure status.
In participants with heart failure: 67 of 342 (semaglutide) vs 88 of 336 (placebo), HR: 0.67; 95% CI: 0.49-0.93
In participants without heart failure: 264 of 1,424 (semaglutide) vs 322 of 1,430 (placebo), HR: 0.79; 95% CI: 0.67-0.93
P for interaction = 0.40
At baseline, 678 of 3,532 participants (19.2%) had heart failure
Number needed to treat to prevent 1 primary kidney outcome at 3 years was 13 in the heart failure subgroup
Results
Semaglutide reduced the primary kidney outcome risk in participants with high total cardiovascular disease risk (PREVENT score ≥20%) who did not have established cardiovascular disease.
In participants with high total CVD risk (PREVENT ≥20%): 134 of 675 (semaglutide) vs 168 of 654 (placebo), HR: 0.73; 95% CI: 0.58-0.91
In participants without high total CVD risk: 44 of 331 (semaglutide) vs 58 of 340 (placebo), HR: 0.73; 95% CI: 0.49-1.08
P for interaction = 0.99
1,329 of 2,000 participants without established cardiovascular disease (66.5%) had a 10-year PREVENT score ≥20%
Number needed to treat to prevent 1 primary kidney outcome at 3 years was 17 in the PREVENT score ≥20% subgroup
Results
Semaglutide reduced all-cause mortality risk consistently across ASCVD subgroups.
In participants with ASCVD: 99 of 593 (semaglutide) vs 121 of 605 (placebo), HR: 0.82; 95% CI: 0.63-1.07
In participants without ASCVD: 128 of 1,174 (semaglutide) vs 158 of 1,161 (placebo), HR: 0.78; 95% CI: 0.62-0.99
P for interaction = 0.79, indicating no significant difference in treatment effect by ASCVD status
Results
Semaglutide reduced all-cause mortality risk in participants with and without heart failure, with no significant interaction.
In participants with heart failure: 64 of 342 (semaglutide) vs 79 of 336 (placebo), HR: 0.75; 95% CI: 0.54-1.05
In participants without heart failure: 163 of 1,424 (semaglutide) vs 200 of 1,430 (placebo), HR: 0.81; 95% CI: 0.66-0.99
P for interaction = 0.74
Results
Semaglutide reduced all-cause mortality risk in participants with high total cardiovascular disease risk (PREVENT score ≥20%) without established cardiovascular disease.
In participants with high total CVD risk (PREVENT ≥20%): 73 of 675 (semaglutide) vs 98 of 654 (placebo), HR: 0.71; 95% CI: 0.52-0.95
In participants without high total CVD risk: 23 of 331 (semaglutide) vs 28 of 340 (placebo), HR: 0.82; 95% CI: 0.47-1.43
P for interaction = 0.63
Methods
The primary composite kidney outcome included multiple clinically meaningful endpoints evaluated across the full FLOW trial population of 3,533 participants with type 2 diabetes and CKD.
Primary outcome components: ≥50% eGFR decline, eGFR <15 mL/min/1.73 m², dialysis, transplantation, and kidney or cardiovascular death
Participants were randomized to once-weekly subcutaneous semaglutide 1.0 mg vs placebo
Trial registration: NCT03819153 (FLOW trial)
All-cause death was a confirmatory secondary outcome
What This Means
This research examined whether a diabetes medication called semaglutide (given as a weekly injection) protects the kidneys and extends survival in people with type 2 diabetes and chronic kidney disease (CKD), specifically looking at whether any benefits differed based on patients' heart health at the start of the study. The FLOW trial enrolled over 3,500 participants and divided them into groups based on whether they had established heart disease (atherosclerosis), heart failure, or a high estimated risk of future heart problems. The study found that semaglutide consistently reduced the risk of serious kidney events — such as severe kidney function loss, need for dialysis, or death from kidney or heart causes — across all cardiovascular subgroups. The number of patients who needed to be treated to prevent one serious kidney event over three years ranged from 13 (in those with heart failure) to 22 (in those with established atherosclerotic heart disease), suggesting meaningful absolute benefit across groups.
Semaglutide also reduced the risk of death from any cause across all subgroups, with hazard ratios generally in the range of 0.71 to 0.82, though some estimates crossed 1.0 (indicating uncertainty in smaller subgroups). Critically, statistical tests for interaction showed no significant differences in how well semaglutide worked based on cardiovascular status — meaning the drug appeared to benefit people whether or not they had pre-existing heart disease or high cardiovascular risk.
This research suggests that semaglutide's kidney-protective and survival benefits in people with type 2 diabetes and CKD are not limited to those who already have established cardiovascular disease — a group that has historically been the focus of such treatments. People with high cardiovascular risk but without a prior heart attack or stroke also appeared to benefit, which could broaden the population that might be considered for this therapy. These findings add to the growing evidence that GLP-1 receptor agonists like semaglutide have important organ-protective effects beyond blood sugar control.
Tuttle K, Bakris G, Baeres F, Bang C, Bax W, Belmar N, et al.. (2026). Kidney and Survival Benefits of Semaglutide in Diabetes With Chronic Kidney Disease: FLOW Trial Cardiovascular Subgroup Analyses.. Journal of the American College of Cardiology. https://doi.org/10.1016/j.jacc.2026.02.5125