Semaglutide Significantly Reduces Risk of Renal Events, MACE, Death in Persons with CKD, T2D: Daily Dose

_{©New Africa/AdobeStock}

Patient Care brings primary care clinicians a lot of medical news every day—it’s easy to miss an important study. The Daily Dose provides a concise summary of one of the website's leading stories you may not have seen.

Last week, we reported on findings from the landmark FLOW trial presented at the 61st European Renal Association Congress, May 23-26, 2024, in Stockholm, Sweden.

The study

Inclusion criteria for the FLOW trial, initiated in 2019, required participants to have an eGFR of 50 to 75 ml/min/1.73m² of body-surface area and a urinary albumin-to-creatinine ratio (UACR) of greater than 300 and less than 5000 or an eGFR of 25 to less than 50 ml/min/1.73m² and a UACR greater than 100 and less than 5000. The randomized, double-blind, parallel-group, placebo-controlled, superiority trial compared the effects of injectable semaglutide 1.0 mg against placebo, administered weekly, as an adjunct to standard of care on kidney outcomes in people with T2D and CKD. The trial’s 5-point composite primary endpoint was:

• Onset of persistent ≥50% reduction in eGFR

• Onset of persistent eGFR decline to <15 mL/min/1.73 m²

• Initiation of chronic kidney replacement therapy

• Death from kidney disease

• Death from cardiovascular disease

The confirmatory secondary endpoints were annual rate of change in eGFR, 3-point major adverse cardiovascular events (MACE), and all-cause death.

Researchers enrolled 3553 participants from 387 study sites in 28 countries for a final study cohort with a mean age of 66.6 years and comprised of 69.7% men. Approximately two-thirds (65.8%) of the participants identified as non-Hispanic White.

Half the cohort was randomly assigned to receive semaglutide 1.0 mg and half to receive placebo. The median follow-up period was 3.4 years.

The findings

Use of semaglutide was associated with a 24% relative risk reduction for the primary outcome of major kidney disease events compared to treatment with placebo (HR 0.76; 95% CI, 0.66 to 0.88; P = .003). Risk reductions relative to placebo for semaglutide were similar for a composite of the kidney-specific components of the primary outcome (HR, 0.79; 95% CI, 0.66 to 0.94) as well as for death from CV causes (HR, 0.71; 95% CI, 0.56 to 0.89).

Results of all the confirmatory secondary outcomes were also more favorable for participants who received semaglutide and included a less steep decline in mean annual eGFR (difference, 1.16 mL/min/1.73m²; P <.001) and a reduced risk of 3-point MACE (HR, 0.82; 95% CI, 0.68 to 0.98; P = .029) and all-cause mortality (HR, 0.80; 95% CI, 0.67 to 0.95; P = .01). Findings from the safety analyses demonstrated a lower rate of serious adverse events among semaglutide- vs placebo-treated FLOW participants (49.6% vs 53.8%).

Authors' comment

"These benefits signify a profound clinical impact saving kidneys, hearts and lives, for patients with type 2 diabetes and chronic kidney disease. Additionally, the reassuring safety findings further support the strong potential value of semaglutide in this population."

Click here for more details.