Am J Med. 2026 Oct 30:S0002-9343(26)00773-4. doi: 10.1016/j.amjmed.2026.10.018. Online ahead of print.
ABSTRACT
Type 2 diabetes is the leading cause of chronic kidney disease worldwide, and for decades renin-angiotensin-system (RAAS) blockade was the only proven strategy to slow its progression. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have since been shown to slow kidney function decline and reduce cardiorenal events through benefits disproportionate to their modest glycemic effect. Beginning with EMPA-REG OUTCOME, and confirmed by CREDENCE, DAPA-CKD, and EMPA-KIDNEY, these agents significantly reduce major cardiorenal composite outcomes, largely independent of diabetes status, through restored tubuloglomerular feedback, reduced intraglomerular pressure, and hemodynamic and metabolic effects. Their safety profile is favorable, dominated by genital mycotic infection, with euglycemic ketoacidosis and, for some agents, amputation as rare but important considerations. Kidney Disease: Improving Global Outcomes, the American Diabetes Association, and the European Society of Cardiology now recommend SGLT2 inhibitors as foundational, disease-modifying therapy in diabetic kidney disease. This review synthesizes that evidence for the practicing internist, whose prescribing choices will determine whether it reaches eligible patients.
PMID:42962953 | DOI:10.1016/j.amjmed.2026.10.018