FLOW-trial: Semaglutide improves kidney and cardiovascular outcomes in type 2 diabetes and chronic kidney disease

The phase 3 FLOW trial confirms: glucagon-like peptide 1 receptor agonist semaglutide has shown significant improvement in kidney and cardiovascular outcomes in participants with type 2 diabetes and chronic kidney disease.

The phase 3, global, randomised, controlled FLOW trial (NCT03819153) randomised 3533 participants 1:1 to semaglutide 1mg weekly or placebo, with all participants receiving background standard-of-care therapy. The trial design, primary, cardiovascular, and safety outcomes were presented by multiple speakers at the ERA 2024 [1–4].

The FLOW trial included adults with type 2 diabetes (HbA1c ≤10%), who had additional chronic kidney disease (eGFR of 50–75 mL/min/1.73 m², urinary albumin-to-creatinine ratio between >300 and <5000 mg/g, or eGFR of 25 to <50 mL/min/1.73 m², urinary albumin-to-creatinine ratio between >100 and <5000 mg/g). The primary endpoint was the time-to-first occurrence of persistent ≥50% eGFR reduction from baseline, kidney failure (persistent eGFR <15 mL/min/1.73 m², dialysis or kidney transplant), kidney-related mortality or cardiovascular death.

The trial was stopped early as it reached the pre-specified boundaries of superiority of the new treatment: After a median of 3.4 years, 18.7% of participants receiving semaglutide reached the primary endpoint compared with 23.2% of participants receiving placebo (HR 0.76; 95% CI 0.66–0.88; P=0.0003). 12.3% of participants with semaglutide versus 14.7% of control participants achieved the composite outcome excluding cardiovascular death (HR 0.79; 95% CI 0.66–0.94), while the mean loss of kidney function rate was -2.19 mL/min/1.73 m²/year compared with -3.36 mL/min/1.73 m²/year (1.16 mL/min/1.73 m²/year difference; P<0.001) [1]. Semaglutide also showed significantly lower rates of major adverse cardiac events (12.0% vs 14.4%; HR 0.82; 95% CI 0.68–0.98; P=0.029) compared to placebo [3]. Overall, serious adverse events were more common in the placebo group (53.8% vs 59.6%), with infections, infestations, and cardiac adverse events as the most common adverse events in both groups [4].

“The FLOW trial demonstrated a 24% lower risk of the primary outcome with the consistency of the kidney components of the primary outcome”, concluded Prof. Vlado Perkovic (University of New South Wales, Sydney, Australia), the lead investigator of the trial [2]. These results are particularly promising in combination with the similar safety outcomes in the two groups.

1. Pratley R, et al. FLOW trial design and baseline characteristics. Plenary Session, ERA 2024, 23–26 May, Stockholm, Sweden.
2. Perkovic V, et al. FLOW primary efficacy results. Plenary Session, ERA 2024, 23–26 May, Stockholm, Sweden.
3. Mahaffey KW, et al. FLOW CV outcomes. Plenary Session, ERA 2024, 23–26 May, Stockholm, Sweden.
4. Mann JFE, et al. FLOW safety outcomes. Plenary Session, ERA 2024, 23–26 May, Stockholm, Sweden.

Medical writing support was provided by Mihai Surducan, PhD.

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Posted on 20 June 202426 July 2024