Semaglutide improves renal outcomes in overweight/obese participants with cardiovascular disease and no diabetes

Semaglutide compared with placebo showed significant renal improvement on top of the recently established cardiovascular improvements in participants with overweight/obesity and cardiovascular disease enrolled in the SELECT trial.

The SELECT trial (NCT03574597) is a randomised, double-blind, multicentre, phase 3 trial of semaglutide versus placebo which enrolled participants with BMI ≥27 kg/m² and established cardiovascular disease but no diabetes to assess cardiovascular outcomes [1]. The current renal prespecified analysis, presented by Prof. Helen M. Colhoun (The University of Edinburgh, United Kingdom), used a 5-point composite endpoint defined as death due to kidney causes, initiation of chronic kidney replacement therapy (dialysis or transplant), onset of persistent eGFR <15 mL/min/1.73 m², persistent eGFR reduction from baseline of ≥50%, or onset of persistent microalbuminuria. These analyses were performed on the entire cohort of SELECT (n=17604) [2].

The time-to-occurrence of the 5-component kidney endpoint was significantly longer with semaglutide compared with placebo. After a median follow-up of 182 weeks, 1.8% of participants receiving semaglutide and 2.2% receiving placebo achieved the composite endpoint (HR 0.78; 95% CI 0.63–0.96; P=0.02). When analysing the individual components of the composite endpoint, the efficacy results were mainly driven by improvement in time-to-onset of eGFR reduction from baseline of ≥50% (HR 0.57; 95% CI 0.27–1.14; P=0.11) and time-to-onset of microalbuminuria (HR 0.80; 95% CI 0.64–1.00; P=0.05). No kidney-related deaths were observed for either group. Semaglutide further led to a treatment benefit of 0.75 mL/min/1.73 m² (95% CI 0.43–0.96; P<0.001) in eGFR and -10.7% (95%CI -13.2 to -8.2; P<0.001) in urinary albumin-creatinine ratio at week 104, compared with placebo.

“In the absence of diabetes, 2.4 mg of semaglutide weekly reduced the composite kidney endpoint by 22% and had beneficial effects on eGFR and urine albumin-creatinine ratio”, summarised Prof. Colhoun. “These data add to the growing body of evidence on the potential kidney benefit of semaglutide”.

1. Lincoff AM, et al. N Engl J Med. 2023;389(24):2221–2232.
2. Colhoun HM, et al. Effect of semaglutide on kidney outcomes in people with overweight or obesity and established cardiovascular disease in the SELECT trial. Abstract #2496, ERA 2024, 23–26 May, Stockholm, Sweden.

Medical writing support was provided by Mihai Surducan, PhD.

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Posted on 20 June 202424 June 2024