%0 Journal Article
%T Cardiovascular protection significantly depends on HbA1c improvement with GLP-1RAs but not with SGLT2 is in type 2 diabetes: A narrative review.
%A Scheen AJ
%J Diabetes Metab
%V 50
%N 2
%D 2024 Mar 28
%M 38158077
%F 8.254
%R 10.1016/j.diabet.2023.101508
%X <B>BACKGROUND: </B>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is), while developed as antihyperglycaemic medications for the treatment of type 2 diabetes, have proven to reduce major cardiovascular adverse events (MACEs) and hospitalization for heart failure (especially for SGLT2is) in dedicated cardiovascular outcome trials. The contribution of the glucose-lowering effect in the cardiovascular protection is uncertain and may differ between the two drug classes.<BR><B>METHODS: </B>This narrative review compares the relative effects of glycated hemoglobin (HbA1c) reduction on the cardiovascular protection provided by GLP-1RAs and SGLT2is in placebo-controlled cardiovascular outcome trials by using the results of either post-hoc mediation analyses or meta-regression studies.<BR><B>RESULTS: </B>Both mediation and meta-regression analyses suggest that the lower cardiovascular risk with GLP-1RAs partially but substantially tracks with their glucose-lowering effect, especially when considering the reduction in nonfatal strokes. In contrast, similar analyses fail to demonstrate any significant contribution of the glucose-lowering effect with SGLT2is, not only on MACEs but also on heart failure issues.<BR><B>CONCLUSIONS: </B>The contribution of improved glucose control in cardiovascular protection is limited, but is much greater for GLP-1RAs than for SGLT2is. Of note, such mediation or meta-regression analyses are exploratory and can only be viewed as hypothesis generating.