Semaglutide has shown significant benefits in reducing major kidney outcomes, cardiovascular events, and mortality in individuals with type 2 diabetes (T2D) and chronic kidney disease (CKD), irrespective of the severity of their CKD. These findings come from the phase 3 FLOW trial, presented at the American Society of Nephrology (ASN) Kidney Week 2024.
The FLOW trial, led by Katherine R. Tuttle, MD, aimed to evaluate kidney outcomes based on baseline CKD severity. The study adds to the growing body of evidence supporting semaglutide's use in various indications, expanding from its initial role as an antihyperglycemic drug to demonstrating benefits in cardiovascular and renal health.
Consistent Kidney Protection Across CKD Severities
"We found that the benefit on kidney outcomes was consistent regardless of CKD severity at study entry," said Dr. Tuttle. The trial's findings suggest that semaglutide offers consistent kidney protection across different stages of CKD in patients with T2D. Further studies are underway to investigate the mechanisms behind this protection and to assess semaglutide's safety and efficacy in CKD patients with type 1 diabetes or without diabetes.
The study involved 3533 participants with T2D, stratified by estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Participants were randomized to receive either subcutaneous semaglutide 1 mg once weekly or a placebo. The mean age of participants was 67 years, with a mean eGFR of 47 mL/min/1.73 m2 and a median UACR of 568 mg/g at baseline. Thirty percent of the participants were women.
The primary outcome of the FLOW trial was a composite of kidney failure, a sustained decline of 50% or more in eGFR, or death due to kidney or cardiovascular causes. Over a median follow-up of 3.4 years, participants treated with semaglutide showed a hazard ratio (HR) of 0.76 (95% CI, 0.66-0.88) for the composite primary outcome compared to those receiving placebo.
Detailed Outcome Analysis
Specifically, the hazard ratios for individual components of the primary outcome in the semaglutide group were as follows:
- Kidney replacement therapy: HR 0.84 (95% CI, 0.63-1.12)
- eGFR persistently below 15 mL/min/1.73m2: HR 0.80 (95% CI, 0.61-1.06)
- Persistent reduction of at least 50% in eGFR: HR 0.73 (95% CI, 0.59-0.89)
- Kidney failure: HR 0.97 (95% CI, 0.27-3.49)
- Cardiovascular death: HR 0.71 (95% CI, 0.56-0.89)
These trends remained consistent across varying eGFR and UACR severity levels, reinforcing the broad applicability of semaglutide in this patient population.
