Insulin efsitora alfa, a novel once-weekly fragment crystallizable (Fc)-fusion basal insulin, may improve treatment convenience while maintaining glycemic control.<h4>Objective</h4>To evaluate the efficacy and safety of once-weekly insulin efsitora alfa compared with once-daily basal insulin analogs in adults with T2DM.<h4>Methods</h4>An updated systematic review and meta-analysis was conducted according to PRISMA 2020 guidelines and registered in PROSPERO (CRD420251118205). This evidence concerns the gene INS and type 2 diabetes mellitus.