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05-06-2024 | Type 2 Diabetes | Editor's Choice | News

Semaglutide shows cardiorenal benefits in type 2 diabetes with chronic kidney disease

Author: Sara Freeman


medwireNews: The glucagon-like peptide (GLP)-1 receptor antagonist semaglutide has both renal and cardioprotective effects in people with type 2 diabetes and chronic kidney disease (CKD) who are at high risk for complications, results of the FLOW trial suggest. 

The randomized clinical trial was stopped early after a median of 3.4 years’ follow-up when the preplanned interim analysis provided “clear conclusions about benefits and risks” supporting the use of semaglutide over placebo, its investigators report.

The study’s findings were published in The New England Journal of Medicine to coincide with their presentation at the European Renal Association Congress in Stockholm, Sweden.

The primary endpoint was the occurrence of major kidney disease events, defined as a composite of the onset of kidney failure (dialysis, transplantation, or a reduced estimated glomerular filtration rate [eGFR] <15 mL/minute per 1.73 m2 sustained for at least 28 days), at least a 50% reduction in the eGFR from baseline sustained for at least 28 days, or death from a kidney- or cardiovascular (CV)-related cause.

The risk for this outcome was a significant 24% lower in the 1767 patients given weekly semaglutide 1.0 mg than the 1766 patients given placebo, with a respective 331 and 410 first events occurring. Vlado Perkovic (University of New South Wales, Sydney, Australia) and colleagues also report that the “results for all confirmatory secondary outcomes favored semaglutide.”  

This included a “less steep” decrease in the mean annual eGFR slope from baseline of –2.29 mL/min per 1.73 m2 for semaglutide, compared with –3.36 mL/min per 1.7 3m2 for placebo, giving a significant between-group difference of –1.16 mL/min per 1.73 m2.

In addition, semaglutide was associated with a significant 18% lower risk than placebo for a first major CV event, defined as a composite of nonfatal myocardial infarction, nonfatal stroke, or death from CV causes (212 vs 254 events).

And the risk for death from any cause was reduced by a significant 20% with semaglutide versus placebo (227 vs 279 deaths).

Safety findings showed that a lower percentage of semaglutide- than placebo-treated participants experienced serious adverse effects, at 49.6% versus 53.8%.

“The magnitude of the benefits observed in our trial provides confidence that the use of semaglutide in patients with type 2 diabetes and chronic kidney disease will reduce the risk of kidney failure and slow the decline in the eGFR, as well as reduce the risk of cardiovascular events and death,” the researchers say.

Whether the benefits extend to other GLP-1 receptor agonists or to participants outside of the population of patients studied remains to be seen, they observe.

The trial involved 3533 participants with type 2 diabetes and CKD, 68% of whom were at very high risk for kidney disease progression, kidney failure, CV events, or death, according to Kidney Disease: Improving Global Outcomes risk calculators. The mean age was 66.6 years, 30.3% were women, and 65.8% were White.

Specifically, the patients had long-standing kidney disease, defined as an eGFR of 25–75 mL/min per 1.73 m2 with a urinary-to-creatinine ratio above 300 and below 5000 if the eGFR was 50 mL/min per 1.73 m2 or above 100 and less than 5000 if the eGFR was 25 to less than 50 mL/min per 1.73 m2.

The researchers report that the number of people who would need to be treated over the course of 3 years to prevent one major kidney disease event was 20, to prevent one major CV event was 45, and to prevent one death from any cause was 39.

“The mechanisms of kidney protection with semaglutide are likely to be multifactorial,” say the researchers, observing that it is “unlikely” to be due to the well-known weight loss effects of the drug.

With other guideline-directed medical therapies available for managing people with type 2 diabetes and CKD, Perkovic et al say that “clinicians and patients will need to consider the order and priority of use” for semaglutide.

They suggest: “Combination therapy is likely to be important in the future.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group

N Engl J Med 2024; doi:10.1056/NEJMoa2403347
61st ERA Congress; Stockholm, Sweden:  23–26 May 2024


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