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Effects of Semaglutide on CKD in Type 2 Diabetes
Quick Takes
- Semaglutide significantly reduced the risk of major kidney disease events, by 24% among patients with type 2 diabetes and chronic kidney disease in the FLOW trial.
- Semaglutide also reduced the risk of major cardiovascular events and death from any cause while slowing the annual loss of kidney function.
- These benefits reflect important clinical effects on kidney, cardiovascular, and survival outcomes among high-risk patients, and support a role for semaglutide in this population.
Study Questions:
What is the efficacy and safety of semaglutide for the prevention of kidney failure, loss of kidney function, and death from kidney-related or cardiovascular causes in patients with type 2 diabetes and chronic kidney disease (CKD)?
Methods:
The FLOW trial investigators randomly assigned patients with type 2 diabetes and CKD (defined by an estimated glomerular filtration rate [eGFR] of 50-75 mL/min/1.73 m2 of body surface area and a urinary albumin-to-creatinine ratio [with albumin measured in milligrams and creatinine measured in grams] of >300 and <5000 or an eGFR of 25 to <50 mL/min/1.73 m2 and a urinary albumin-to-creatinine ratio of >100 and <5000) to receive subcutaneous semaglutide at a dose of 1.0 mg weekly or placebo. The primary outcome was major kidney disease events, a composite of the onset of kidney failure (dialysis, transplantation, or an eGFR of <15 mL/min/1.73 m2), ≥50% reduction in the eGFR from baseline, or death from kidney-related or cardiovascular causes. Prespecified confirmatory secondary outcomes were tested hierarchically. Time-to-first-event outcomes were analyzed with a stratified Cox proportional-hazards model with randomization assignment (semaglutide or placebo) as a fixed factor and stratified according to sodium-glucose cotransporter-2 (SGLT2) inhibitor use at baseline.
Results:
Among the 3,533 participants who underwent randomization (1,767 in the semaglutide group and 1,766 in the placebo group), median follow-up was 3.4 years, after early trial cessation was recommended at a prespecified interim analysis. The risk of a primary outcome event was 24% lower in the semaglutide group than in the placebo group (331 vs. 410 first events; hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.66-0.88; p = 0.0003). Results were similar for a composite of the kidney-specific components of the primary outcome (HR, 0.79; 95% CI, 0.66-0.94) and for death from cardiovascular causes (HR, 0.71; 95% CI, 0.56-0.89). The results for all confirmatory secondary outcomes favored semaglutide: the mean annual eGFR slope was less steep (indicating a slower decrease) by 1.16 mL/min/1.73 m2 in the semaglutide group (p < 0.001), the risk of major cardiovascular events 18% lower (HR, 0.82; 95% CI, 0.68-0.98; p = 0.029), and the risk of death from any cause 20% lower (HR, 0.80; 95% CI, 0.67-0.95, p = 0.01). Serious adverse events were reported in a lower percentage of participants in the semaglutide group than in the placebo group (49.6% vs. 53.8%).
Conclusions:
The authors report that semaglutide reduced the risk of clinically important kidney outcomes and death from cardiovascular causes in patients with type 2 diabetes and CKD.
Perspective:
This trial of patients with type 2 diabetes and CKD reports that semaglutide significantly reduced the risk of major kidney disease events, by 24%. Furthermore, semaglutide reduced the risk of major cardiovascular events and death from any cause while slowing the annual loss of kidney function. These benefits reflect important clinical effects on kidney, cardiovascular, and survival outcomes among high-risk patients, and support a role for semaglutide in this population. Because three other therapies have been shown to have benefits in patients with type 2 diabetes and CKD (renin-angiotensin system inhibition, SGLT2 inhibition, and mineralocorticoid with finerenone), clinicians will need to consider the order and priority of use for semaglutide and will need to individualize therapy with a possible role for combination of these agents.
Clinical Topics: Diabetes and Cardiometabolic Disease
Keywords: Cardiometabolic Diseases, Renal Insufficiency, Chronic, Sodium-Glucose Transporter 2 Inhibitors
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