The growing clinical effect of SGLT2 inhibitors

Abstract

In September, 2015, the results of EMPA-REG OUTCOME, the first cardiovascular outcomes study based on a sodium-glucose co-transporter-2 (SGLT2) inhibitor, empagliflozin, were announced at the Annual Meeting of the European Association for the Study of Diabetes. It was the first of a series of cardiovascular outcome studies confirming a significant risk reduction of the three-point MACE (cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke) in people with type 2 diabetes and established atherosclerotic cardiovascular disease. It was also the first clinical trial to show potential renal protection: empagliflozin was associated with reduced loss of estimate glomerular filtration rate compared with placebo. Moreover, the trial reported a significant reduction in the risk of hospitalisation for heart failure. 1 Zinman B Wanner C Lachin JM et al. Investigators E-ROEmpagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015; 373: 2117-2128 Crossref PubMed Scopus (7211) Google Scholar The cardiorenal protective effects of SGLT2 inhibitors have been confirmed in subsequent cardiovascular outcomes studies done in people with type 2 diabetes 2 McGuire DK Shih WJ Cosentino F et al. Association of SGLT2 inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes: a meta-analysis. JAMA Cardiol. 2021; 6: 148-158 Crossref PubMed Scopus (339) Google Scholar and without diabetes. 3 Vaduganathan M Docherty KF Claggett BL et al. SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials. Lancet. 2022; 400: 757-767 Summary Full Text Full Text PDF PubMed Scopus (61) Google Scholar Because of these results, current guidelines recommend the use of a SGLT2 inhibitor with proven beneficial effect for people with type 2 diabetes with chronic kidney disease and a history of heart failure. 4 Davies MJ Aroda VR Collins BS et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2022; 65: 1925-1966 Crossref PubMed Scopus (32) Google Scholar Effects of dapagliflozin on hospitalisations in people with type 2 diabetes: post-hoc analyses of the DECLARE-TIMI 58 trialDapagliflozin reduced the risk of first and total non-elective hospitalisations for any cause in people with type 2 diabetes, regardless of the presence of atherosclerotic cardiovascular disease, including hospitalisations not directly attributed to cardiac, kidney, or metabolic causes. These findings might have implications on health-related quality of life for people with type 2 diabetes and on health-care costs attributable this condition. Full-Text PDF