Study Finds Semaglutide Improves Chronic Kidney Disease in Patients With Type 2 Diabetes

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Article

The role of semaglutide as a glucagon-like peptide-1 (GLP-1) receptor antagonist could offer further treatment options to improve patient outcomes.

New research published in The New England Journal of Medicine announced that semaglutide (Wegovy: Novo Nordisk) could reduce the risk of clinically important kidney outcomes and death caused by cardiovascular issues among individuals with type 2 diabetes and chronic kidney disease (CKD). The results were found in the international, double-blind, randomized, place-controlled FLOW trial, which assessed the safety and efficacy of a 1.0 mg dose of semaglutide weekly.1

Woman holding an injection pen for diabetic - Image credit: nazif | stock.adobe.com

Image credit: nazif | stock.adobe.com

The study authors noted that more than half a billion individuals are affected by CKD and are at high risk for kidney failure, cardiovascular events, and death — with type 2 diabetes as the main cause. Treatment options like Renin–angiotensin system (RAS) inhibitors, sodium–glucose cotransporter 2 (SGLT2) inhibitors, and finerenone have been reported to protect kidneys and reduce the risk of cardiovascular outcomes. However, despite these therapies, numerous individuals continue to lose kidney function, experience kidney failure, or die.1

Semaglutide, as a glucagon-like peptide-1 (GLP-1) receptor antagonist, could offer further treatment options to improve patient outcomes.2 The FDA recently approved a new indication for the use of semaglutide to reduce the risk of cardiovascular death, heart attack, and stroke among individuals with cardiovascular disease.2

“The use of GLP-1 receptor agonists in broader populations with type 2 diabetes has previously been shown to improve glycemic control, decrease body weight, and reduce cardiovascular events. However, previous dedicated trials addressing clinically important kidney outcomes, such as kidney failure or a substantial decline in the eGFR, have been lacking,” said study authors in a news release.1

The FLOW trial included 3533 individuals with type 2 diabetes who were eligible for inclusion if they experienced high-risk CKD and were receiving a maximal dose of RAS inhibitors, according to study authors.1 The individuals were randomly assigned to receive semaglutide or placebo. The study authors noted that an 8-week dose escalation regimen was used, increasing from 0.25 mg per week for 4 weeks to 0.5 mg per week for 4 weeks, then continuing with a 1.0 mg maintenance dose until the end of the study. The median follow-up was 3.4 years.1

The results showed that the primary outcome of major kidney disease events, a composite of onset of kidney failure, was 24% lower among individuals treated with semaglutide compared with the placebo group (331 vs. 410 first events; HR 0.76; 95% CI, 0.66 to 0.88; P=0.0003). Additionally, semaglutide displayed favorable results over the placebo group among kidney-specific components and death from cardiovascular causes, according to study authors.1

Furthermore, confirmatory secondary outcomes were also greater among individuals in the semaglutide group with a slower decrease in the mean annual eGFR slope by 1.16 ml per minute per 1.73 m2, and a 18% lower risk of major cardiovascular events.1

Serious adverse events were reported to be fewer among individuals in the semaglutide group compared with individuals in the placebo group (877 [49.6%] vs. 950 [53.8%]).1 However, the study authors noted that this could be due to less infections or serious cardiovascular disorders in the semaglutide group.2

However, limitations in the study included limited ability of the effects of combination therapy and a lack of detecting differences between important subgroups.1

“Our trial has important strengths. This trial of a GLP-1 receptor agonist in a population of patients with chronic kidney disease and type 2 diabetes assessed clinically important outcomes, and significant benefits were shown for kidney and cardiovascular outcomes and death from any cause,” said study authors in the news release.1

References
1. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. The New England Journal of Medicine. News release. May 24, 2024. Accessed May 24, 2024. https://www.nejm.org/doi/full/10.1056/NEJMoa2403347?logout=true.
2. FDA Approves Semaglutide for New Indication Involving Cardiovascular Disease. Pharmacy Times. News release. March 8, 2024. Accessed May 24, 2024. https://www.pharmacytimes.com/view/fda-approves-semaglutide-for-new-indication-involving-cardiovascular-disease.

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