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Semaglutide Significantly Reduces Risk of Renal Events, MACE, Mortality in People with CKD, T2D in Final FLOW Trial Findings

News
Article

The pluripotent GLP-1 mimetic reduced risk for renal disease endpoints by 24% and MACE by 18% plus significantly retarded decline in eGFR vs placebo, study authors reported.

Treatment with semaglutide 1.0 mg (Ozempic; Novo Nordisk) in adults with type 2 diabetes and (T2D) chronic kidney disease (CKD) significantly reduced the risk of a composite of renal outcomes and death from both kidney-specific and cardiovascular causes by 24%, according to a full readout of data from the landmark FLOW trial presented at the 61st European Renal Association (ERA) Congress, May 23-26, 2024, in Stockholm, Sweden.1

Semaglutide Significantly Reduces Risk of Renal Events, MACE, Mortality in People with CKD, T2D in Final FLOW Findings  / image credit semaglutide generic: ©Peter Hansen/stock.adobe.com
©Peter Hansen/stock.adobe.com

Study participants treated with the pluripotent GLP-1 mimetic also experienced a reduction in progression of CKD, reflected by slower decline in eGFR, compared with placebo, as well as a 21% reduction in risk of renal-specific components of the primary composite outcome.2

Moreover, investigators reported an 18% lower risk of MACE in semaglutide-treated participants and a reduced risk of death from any cause of 20% vs placebo. The full findings were simultaneously published in the New England Journal of Medicine.2

The presentation of the full data from the FLOW trial follows a topline readout in March 2024,3 an announcement expedited given the early discontinuation of the trial in October 2023.4 That decision was based on recommendation from the trial’s independent Data Monitoring Committee that stated an interim analysis had met the prespecified criteria for stopping the trial early for efficacy.4

“These findings offer great promise in reshaping treatment strategies for individuals at high risk of diabetes-related complications, offering a new avenue for kidney and cardiovascular protection,” presenting author professor Vlado Perkovic, MBBS, PhD, provost of the University of New South Wales in Sydney, Australia, said in an ERA statement.1

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 5000.2 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.2 The trial’s 5-point composite primary endpoint was2:

  • 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.

Perkovic and colleagues 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.2

FINAL STUDY FINDINGS2

As noted, 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%).2

“The use of semaglutide in people with type 2 diabetes and chronic kidney disease can lower the risk of major kidney outcomes and reduce the risk of cardiovascular events, cardiovascular death and all-cause death," Perkovic said. "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.”1


References
1. 61st ERA Congress: Semaglutide significantly reduces risk of major kidney disease events, cardiovascular outcomes and mortality in patients with type 2 diabetes and chronic kidney disease, groundbreaking study reveals. News release. European Renal Association. May 24, 2024. Accessed May 24, 2024. https://www.prnewswire.com/news-releases/61st-era-congress-semaglutide-significantly-reduces-risk-of-major-kidney-disease-events- cardiovascular-outcomes-and-mortality-in-patients-with-type-2-diabetes-and-chronic-kidney-disease-groundbreaking-study-reveals-302152720.html
2. Perkovic V, Tuttle KR, Rossing P, et al, for the FLOW Trial Committee and Investigators. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med. Published online May 24, 2024. https://www.nejm.org/doi/pdf/10.1056/NEJMoa2403347
3. Halsey G. Semaglutide reduces CKD-related Events by 24% in population with T2D and CKD: FLOW findings announced. Patient Care. March 5, 2024. https://www.patientcareonline.com/view/semaglutide-reduces-ckd-related-events-by-24-in-population-with-t2d-and-ckd-flow-findings-announced
4. Halsey G. Novo stops semaglutide kidney outcomes trial early for efficacy. Patient Care. October 11, 2023. https://www.patientcareonline.com/view/novo-stops-semaglutide-kidney-outcomes-trial-early-for-efficacy

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