Multiorgan protective therapy for CKM syndrome: the role of GLP-1-based therapies and SGLT2 inhibitors

For many years risk-modifying therapy targeted individual aspects of CKM syndrome. Statins target dyslipidaemia and atherosclerotic risk (i.e. C&M), and renin-angiotensin-system (RAS) inhibitors target hypertension, heart failure complications and risk of kidney outcomes (C&K). This review focuses on two newer drug classes - glucagon-like peptide-1 (GLP-1)-based therapies and sodium-glucose co-transporter 2 (SGLT2) inhibitors - which are now prescribed alongside these older therapies to further improve C, K and M clinical outcomes in type 2 diabetes. Both treatments are well-established for use in patients with type 2 diabetes due to clear evidence that they reduce risks of cardiovascular disease and kidney outcomes in patients with type 2 diabetes, including those with albuminuric diabetic kidney disease, in whom both therapies should be used irrespective of glycaemic control. GLP-1-based therapies are also employed for their potent weight-lowering effects in people with and without diabetes. SGLT2 inhibitors have broad indications across the CKM spectrum including patients with any of: type 2 diabetes, heart failure (irrespective of ejection fraction) or chronic kidney disease (irrespective of diabetes status and level of albuminuria). SGLT2 inhibitors are well-tolerated and increasingly low-cost. They reduce risk of kidney failure and hospitalisation for heart failure, with relative effects on these outcomes versus placebo appearing larger in magnitude than effects achieved with GLP-1-based therapies. SGLT2 inhibitors, however, have little effect on body fat or atherosclerotic outcomes, unlike GLP-1-based therapies. Differing mechanisms of action and differing effects on different clinical outcomes suggest the two drug classes are complementary and should encourage use in combination.