Review

A 2026 comprehensive review in Drug Design, Development and Therapy (DOI: 10.2147/DDDT.S581491) establishes that semaglutide's cardiorenal benefits operate through five mechanistically distinct pathways: GLP-1 receptor–mediated natriuresis, TLR4/NF-κB and NLRP3 inflammasome suppression, TGF-β fibrosis attenuation, RAAS downregulation, and direct reduction of glomerular hyperfiltration—converging to slow eGFR decline, reduce proteinuria, and improve hard cardiovascular endpoints.

A 2026 comprehensive review synthesising data from the SURPASS, SURMOUNT, and SUMMIT trial programmes establishes that tirzepatide — the first approved dual GIP/GLP-1 receptor co-agonist — produces clinically meaningful benefits across cardiovascular, hepatic, renal, and musculoskeletal domains, extending its therapeutic relevance well beyond glycaemic control and weight reduction alone.

A 2026 narrative review in Pharmaceuticals (MDPI) concludes that semaglutide's cardiovascular benefits are mechanistically distinct from glycemic lowering, operating through NF-κB suppression, AMPK activation, and endothelial preservation. Its oncogenic risk profile remains species-specific and context-dependent: rodent thyroid C-cell data do not translate to confirmed human carcinogenicity, while emerging evidence suggests net anti-proliferative signalling in several obesity-associated tumour types.