Vnitr Lek 2026, 72(6):388-394 | DOI: 10.36290/vnl.2026.072

Sequencing and combination of therapies in the cardiovascular-kidney-metabolic syndrome: GLP-1 RA, SGLT2 inhibitors, lipid-lowering drugs and mineralocorticoid receptor antagonists

Michal Dubský

Centrum diabetologie, Institut klinické a experimentální medicíny, Praha

Cardiovascular-kidney-metabolic (CKM) syndrome is a concept introduced by the 2023 consensus statement of the American Heart Association (AHA). It describes an interconnected complex of obesity, type 2 diabetes mellitus (T2DM), dyslipidemia, chronic kidney disease (CKD), and cardiovascular (CV) disease, including heart failure (HF). Current evidence from large randomized trials supports early sequencing and, in appropriately selected patients, combination of several therapeutic classes: SGLT2 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), lipid-lowering therapies (statins, ezetimibe, PCSK9 inhibitors, inclisiran, bempedoic acid), and the nonsteroidal mineralocorticoid receptor antagonist finerenone. The benefits of these drug classes are complementary in several clinical scenarios, whereas direct evidence for additive effects across all combinations remains limited. Data from the CONFIDENCE trial support the safety and albuminuria-lowering effect of the simultaneous initiation of finerenone and empagliflozin; however, its impact on hard clinical endpoints requires further data. This review summarizes the pathophysiology of CKM syndrome, the evidence for individual drug classes, and a practical algorithm for their combination. Particular attention is paid to the newly published 2026 ACC/AHA U.S. guidelines for the treatment of dyslipidemia in comparison with the 2025 ESC/EAS European update and the KDIGO 2026 draft.

Keywords: cardio-renal-metabolic syndrome, dyslipidaemia, finerenone, GLP-1 receptor agonists, inclisiran, PCSK9 inhibitors, SGLT2 inhibitors, treatment sequencing.

Accepted: September 15, 2026; Published: October 2, 2026  Show citation