Semaglutide Shows Benefit in CKD and Type 2 Diabetes Across Kidney Disease Severities

Katherine R. Tuttle, MD

Credit: UW Medicine

Semaglutide was well-tolerated and reduced risks of major kidney outcomes, cardiovascular events, and death in people with type 2 diabetes (T2D) and chronic kidney disease (CKD), regardless of CKD severity.¹

The phase 3 FLOW trial, one of the latest in the growing roster of studies assessing semaglutide for its effect on a number of outcomes, aimed to assess kidney outcomes by baseline CKD severity.

The new findings were presented at The American Society of Nephrology (ASN) Kidney Week 2024 in San Diego, California, held October 23-26, by Katherine R. Tuttle, MD, Clinical Professor of Medicine, University of Washington Medicine, and Executive Director for Research, Providence Health Care, and Regional Co-Principal Investigator, Institute of Translational Health Sciences, Providence Medical Research Center.

“We found that the benefit on kidney outcomes was consistent regardless of CKD severity at study entry,” Tuttle said.² “Ongoing studies are investigating the mechanisms of kidney protection by semaglutide, and whether semaglutide is also safe and efficacious for CKD in persons with type 1 diabetes or those without diabetes.”

The new findings only add to the body of literature supporting semaglutide’s use in a number of indications, in an ever-growing expansion from the therapy’s start as an antihyperglycemic drug to showing benefits in cardiovascular, and now renal, health.³

Tuttle and colleagues analyzed data from 3533 participants with T2D stratified by estimated glomerular filtration rate (GFR) levels between 50–75 mL/min/1.73m2 and urine albumin–creatinine ratios (UACR) between 300 and 5000 mg/g, or eGFR between 25 and 50 mL/min/1.73m2 and UACR >100–<5000 mg/g. Participants were randomized to subcutaneous semaglutide 1 mg once weekly or placebo. Participants had a mean age of 67 years, a mean eGFR of 47 mL/min/1.73 m2, and a median UACR of 568 mg/g at baseline. Thirty percent (n = 1069) were women.^q

The FLOW trial’s primary outcome was a composite of kidney failure, over a 50% eGFR decline, or death due to kidney or cardiovascular causes. The investigators found that across eGFR and UACR categories, participants receiving semaglutide had an overall hazard ratio (HR) of 0.76 (95% CI, 0.66-0.88) in the composite primary outcome compared with those receiving placebo over a median of 3.4 years.^q

Specifically, participants receiving semaglutide had an 0.84 HR (95% CI, 0.63-1.12) of kidney replacement therapy, a 0.80 HR (95% CI, 0.61-1.06) of eGFR levels persistently below 15% mL/min/1.73m2, a 0.73 HR of (95% CI, 0.59-0.89) of persistent at least 50% reductions in eGFR, a 0.97 HR (95% CI, 0.27-3.49) of kidney failure, and a 0.71 HR (95% CI, 0.56-0.89) of cardiovascular death compared to those receiving placebo. These trends remained consistent across eGFR and uACR severity levels.¹

REFERENCES

1. Tuttle KR, Mann JF, Rayner B, et al. Semaglutide Reduced Risks of Major Kidney Outcomes Irrespective of CKD Severity in the FLOW Trial. Presented at: ASN Kidney Week 2024, October 23-26; San Diego, California.

2. American Society of Nephrology. High-Impact Clinical Trials Generate Promising Results for Improving Kidney Health: Part 2. Newswise. October 26, 2024. Accessed October 26, 2024. https://www.newswise.com/articles/high-impact-clinical-trials-generate-promising-results-for-improving-kidney-health-part-2.

3. Campbell P. Semaglutide: The drug of today and a steppingstone to Tomorrow. HCP Live. December 6, 2023. Accessed October 25, 2024. https://www.hcplive.com/view/semaglutide-drug-today-steppingstone-tomorrow.