THE LATEST findings from the FLOW trial, the first dedicated kidney outcomes trial with semaglutide in patients with Type 2 diabetes (T2D) and chronic kidney disease (CKD), were presented at the European Association for the Study of Diabetes (EASD) in Madrid, Spain.
One in 10 people are diagnosed with CKD in the general population, with CKD expected to be the 5th most common cause of death worldwide by 2040. CKD heavily contributes to the mortality burden in T2D.
Cardiovascular (CV) outcomes trials have suggested that glucagon-like peptide-1 receptor agonists, such as semaglutide, may affect kidney-related outcomes in people with T2D. Dedicated kidney outcomes trials, like FLOW, are needed to confirm the renoprotective effects of GLP-1RAs.
FLOW is a global, multinational, randomised controlled trial conducted across 28 countries, 387 sites, and 3,533 participants. Adults with T2D and CKD were randomised 1:1 to receive once weekly semaglutide 1.0 mg and standard of care (mean age: 66.6 years, 29.4% female; 65.4% White), or placebo and standard of care (mean age: 66.7 years, 31.1% female; 66.1% White). Approximately 19% of people admitted into the trial had heart failure, 23% had experienced previous myocardial infarction or stroke, and 80% were using lipid-lowering drugs. Median follow-up duration was 3.4 years.
The primary composite kidney outcome was time to first occurrence of major kidney outcomes, including onset of persistent ≥50% reduction in eGFR compared to baseline, kidney failure (initiation of chronic kidney replacement therapy or onset of persistent eGFR <15 mL/min/1.73 m2), kidney death, or CV death. Secondary outcomes included total eGFR slope; major adverse cardiovascular events (MACE), including CV death, non-fatal myocardial infarction, or non-fatal stroke; and all-cause death.
Results revealed that semaglutide decreased the risk of the composite primary outcome by 24% (95% CI: 0.66–0.88; P=0.0003). Importantly, the benefits of semaglutide were independent of clinically relevant subgroups (sex, age, BMI, diabetes duration, or HbA1c). There was also no statistically significant difference in the effects of semaglutide across patients on different background medications, such as insulin, metformin, or SGLT2 inhibitors.
Furthermore, semaglutide reduced decline in eGFR by 1.16 mL/min/1.73 m2/year (95% CI: 0.86–1.47; P<0.001) and reduced urine albumin-to-creatinine ratio (UACR) by 32% (95% CI: 0.62–0.75) compared to placebo. Semaglutide also significantly decreased the risk of MACEs by 18% (95% CI: 0.68–0.98; P=0.029), and reduced all-cause mortality by 20% compared to placebo (95% CI: 0.67–0.95; P=0.010).
Semaglutide-treated patients experienced fewer serious adverse events compared to placebo (49.6% versus 53.8%), but slightly more adverse events leading to permanent trial product discontinuation (13.2% versus 11.9%).
Beyond meeting the primary composite kidney outcome, semaglutide was found to have a substantial CV benefit in patients with T2D and CKD. Further research will be needed to assess whether the benefits of semaglutide can also apply to individuals with CKD who do not have T2D.
Ada Enesco, EMJ
Reference
Rossing P et al. FLOW: the first dedicated kidney outcomes trial with GLP-1 RA, semaglutide, in patients with type 2 diabetes and CKD. S24. EASD Annual Meeting, 9–13 September, 2024.
