Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial

This study investigated the effects of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), with and without concomitant sodium-glucose cotransporter-2 inhibitor (SGLT2i) use in participants with type 2 diabetes (T2D) and chronic kidney disease (CKD). The FLOW trial (NCT03819153) randomized participants to semaglutide or placebo, stratified by baseline SGLT2i use. The primary outcome was a composite of kidney failure, ≥50% eGFR reduction, kidney death, or CV death. Semaglutide reduced the risk of the primary outcome by 24% overall. In the subgroup without baseline SGLT2i use, semaglutide showed a significant benefit; however, this benefit was not observed in the subgroup using SGLT2i at baseline. Benefits on major CV events and all-cause death were similar regardless of SGLT2i use. The study concludes that semaglutide benefits kidney outcomes regardless of baseline SGLT2i, though power was limited to detect smaller effects. The combination of semaglutide with SGLT2i may be considered for treating patients with T2D and CKD.

Johannes F. E. Mann, Peter Rossing, George Bakris, Nicolas Belmar, Heidrun Bosch-Traberg, Robert Busch, David M. Charytan, Samy Hadjadj, Pieter Gillard, José Luis Górriz, Thomas Idorn, Linong Ji, Kenneth W. Mahaffey, Vlado Perkovic, Søren Rasmussen, Roland E. Schmieder, Richard E. Pratley, Katherine R. Tuttle