{"id":"doi:10.1038/s41591-024-03133-0","kind":"article","title":"Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial","authors":["Mann JFE","Rossing P","Bakris G","Belmar N","Bosch-Traberg H","Busch R","Charytan DM","Hadjadj S","Gillard P","Górriz JL","Idorn T","Ji L","Mahaffey KW","Perkovic V","Rasmussen S","Schmieder RE","Pratley RE","Tuttle KR"],"author_count":18,"year":2024,"published":"2024-06-24","venue":"Nature medicine","cited_by":150,"doi":"10.1038/s41591-024-03133-0","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41591-024-03133-0","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41591-024-03133-0","updated":null,"pmid":"38914124","pmcid":"PMC11485243","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC11485243/pdf","abstract":"People with type 2 diabetes and chronic kidney disease have a high risk for kidney failure and cardiovascular (CV) complications. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors (SGLT2i) independently reduce CV and kidney events. The effect of combining both is unclear. FLOW trial participants with type 2 diabetes and chronic kidney disease were stratified by baseline SGLT2i use (N = 550) or no use (N = 2,983) and randomized to semaglutide/placebo. The primary outcome was a composite of kidney failure, ≥50% estimated glomerular filtration rate reduction, kidney death or CV death. The risk of the primary outcome was 24% lower in all participants treated with semaglutide versus placebo (95% confidence interval: 34%, 12%). The primary outcome occurred in 41/277 (semaglutide) versus 38/273 (placebo) participants on SGLT2i at baseline (hazard ratio 1.07; 95% confidence interval: 0.69, 1.67; P = 0.755) and in 290/1,490 versus 372/1,493 participants not taking SGLT2i at baseline (hazard ratio 0.73; 0.63, 0.85; P < 0.001; P interaction 0.109). Three confirmatory secondary outcomes were predefined. Treatment differences favoring semaglutide for total estimated glomerular filtration rate slope (ml min -1 /1.73 m 2 /year) were 0.75 (-0.01, 1.5) in the SGLT2i subgroup and 1.25 (0.91, 1.58) in the non-SGLT2i subgroup, P interaction 0.237. Semaglutide benefits on major CV events and all-cause death were similar regardless of SGLT2i use (P interaction 0.741 and 0.901, respectively). The benefits of semaglutide in reducing kidney outcomes were consistent in participants with/without baseline SGLT2i use; power was limited to detect smaller but clinically relevant effects. ClinicalTrials.gov identifier: NCT03819153 .","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial\" by Mann JFE, Rossing P, Bakris G et al., https://doi.org/10.1038/s41591-024-03133-0, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"glp1-metabolic","name":"GLP-1 & Incretin Therapies","domain_slug":"medicine"}],"cited_in_dossiers":[{"slug":"glp1-metabolic","title":"GLP-1 & Incretin Therapies: State of the Field (October 2026)","url":"https://space-kitty.com/dossiers/glp1-metabolic"}]}