Study Reveals Robust Benefits of Semaglutide in Protecting Against Kidney, CV Events in Patients With T2D

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Semaglutide reduced the risk of major kidney disease and cardiovascular (CV) events, and death from any cause, while simultaneously decelerating the loss of kidney function, among patients with type 2 diabetes (T2D) and CKD compared to placebo.

Semaglutide may lower the risk of kidney failure and decelerate worsening kidney function, as well as protect against the risk of cardiovascular events and death, among patients with type 2 diabetes (T2D) and chronic kidney disease (CKD), according to results of a new study published in The New England Journal of Medicine.1

Group of dosing pens used for subcutaneous injection of semaglutide / Andreas Prott - stock.adobe.com

Group of dosing pens used for subcutaneous injection of semaglutide / Andreas Prott - stock.adobe.com

Although previous research has established renin–angiotensin system inhibitors, sodium–glucose cotransporter 2 inhibitors, and finerenone as guideline-directed medical therapies to protect the kidneys and reduce the risk of cardiovascular events among patients with CKD and T2D, the effects of glucagon-like peptide 1 (GLP-1) receptor agonists are not well understood. With these medications now more popular than ever due to an increased patient demand, investigators aimed to assess whether treatment with semaglutide could offer patients similar protection against kidney failure, cardiovascular events, and death in patients with CKD and T2D.

About FLOW

Trial Name: Effect of Semaglutide Versus Placebo on the Progression of Renal Impairment in Subjects With Type 2 Diabetes and Chronic Kidney Disease

Clinicaltrials.gov Identifier: NCT03819153

Sponsor: Novo Nordisk A/S

Summary: The researchers are doing this study to see if semaglutide can slow down the growth and worsening of chronic kidney disease in people with type 2 diabetes.

In the international, double-blind, randomized, placebo-controlled, phase 3 FLOW (Evaluate Renal Function with Semaglutide Once Weekly [NCT03819153]) trial, investigators recruited 3533 patients with T2D and a high-risk of CKD. Of this study population, 1767 were randomly assigned to the semaglutide group and 1766 were randomly assigned to the placebo group.

Investigators administered an 8-week dose-escalation regimen to participants. For the first 4 weeks, participants were given 0.25 mg of either semaglutide or a matching placebo, followed by 0.5 mg semaglutide or placebo for another 4 weeks. Following the 8-week period, participants were given a maintenance dose of 1 mg per week for the remainder of the treatment period.

The primary outcomes were major kidney disease events, a composite of onset of kidney failure, a sustained 50% or greater reduction in estimated glomerular filtration rate (eGFR) from baseline, or death from kidney-related or cardiovascular causes, and safety was assessed by collecting data on all serious adverse events.

Following the recruitment period from June 2019 through May 2021 and the subsequent onset of the trial, investigators noted that in October 2023, the trial reached a pre-defined point for a single interim analysis after 570 primary-outcome events had occurred. Based on an evaluation of data from the analysis by an independent committee, the trial was completed early due to sufficient evidence of efficacy. The final participant visit occurred on January 9, 2024, and the median participant follow-up was 3.4 years.

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Participants in the semaglutide group experienced fewer primary outcome events compared to those in the placebo group. There were 331 first events in the semaglutide group, while the placebo group had 410 first events; this translated to a 24% reduction in the relative risk of the primary outcome for those taking the GLP-1 (HR, 0.76; 95% CI, 0.66-0.88; P =.0003).

Participants in the semaglutide group were also less likely to experience a composite of the kidney-specific components of the primary outcomes (HR, 0.79; 95% CI, 0.66-0.94), or death from cardiovascular causes (HR, 0.71; 95% CI, 0.56-0.89).

Assessments of 3 secondary confirmatory outcomes further showed benefit from semaglutide in protecting against adverse kidney and cardiovascular events.

Participants in the semaglutide group experienced a slower decline in eGFR than in the placebo group (−2.19 vs −3.36 mL/min/1.73 m2 per year; between-group difference, 1.16; 95% CI, 0.86-1.47; P <.001), indicating that semaglutide was able to decelerate the worsening of kidney function by a mean of 1.16 mL/min/1.73 m2.

Furthermore, the risk of major cardiovascular events was 18% lower in the semaglutide group than in the placebo group (212 vs 254 events; HR, 0.82; 95% CI, 0.68-0.98; P =.029) The risk of death from any cause was even lesser (20%) in the semaglutide group than in the placebo group (227 vs 279 events; HR, 0.80; 95% CI, 0.67-0.95, P =.01).

Whereas serious adverse events were reported less frequently among participants in the semaglutide group than the placebo group (49.6% vs 53.8%), investigators noted that those related to eye disorders (3.0% vs 1.7%) and permanent discontinuation of semaglutide or placebo (13.2% vs 11.9%) were more common in the former.

“These benefits reflect important clinical effects on kidney, cardiovascular, and survival outcomes among high-risk patients, particularly given the reassuring safety findings, and support a therapeutic role for semaglutide in this population,” wrote investigators.

CKD affects over half a billion people worldwide, putting them at significant risk for kidney failure, cardiovascular events, and death.2 This risk is especially high for those who also have T2D, making them among the patient populations most vulnerable for cardiovascular complications.

Considering this critical health concern, the current study offers robust insights. By investigating the effects of semaglutide—especially against the fast-paced landscape of the medication—it highlights the potential therapeutic intervention for this high-risk population. The study’s findings could pave the way for improved treatment options and potentially lead to better outcomes for millions of people struggling with the complex combination of conditions.

READ MORE: Diabetes Resource Center

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References
1. Perkovic V, Tuttle KR, Rossing P, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. NEJM. Published online May 24, 2024. doi:10.1056/NEJMoa2403347
2. GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020;395(10225):709-733. doi:10.1016/S0140-6736(20)30045-3
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