Comparison of mechanisms and transferability of outcomes of SGLT2 inhibition between type 1 and type 2 diabetes

Abstract

Diabetes mellitus (DM) is a major chronic disease with ever-increasing prevalence and a variety of serious complications for persons with DM, such as cardiovascular and/or renal complications. New glucose-lowering therapies like DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT-2 inhibitors have undergone cardiovascular outcome trials (CVOTs) for type 2 diabetes (T2DM), as by the guidance of the FDA. However, CVOTs for type 1 diabetes (T1DM) are generally lacking. Both, persons with T1DM and T2DM, are burdened with a high incidence of cardiovascular and renal disease such as atherosclerotic cardiovascular disease (ASCVD) and diabetic kidney disease (DKD). Although pathologies of the two types of diabetes cannot be compared, similar mechanisms and risk factors like sex, hyperglycaemia, hypertension, endothelial damage and (background) inflammation have been identified in the development of CVD and DKD in T1DM and T2DM. Recent CVOTs in T2DM demonstrated that SGLT-2 inhibitors, besides exerting a glucose-lowering effect, have beneficial effects on cardiovascular and renal mechanisms. These mechanisms are reviewed in detail in this manuscript and evaluated for possible transferability to, and thus efficacy in, T1DM. Our review of current literature suggests that SGLT-2 inhibitors have cardioprotective benefits beyond their glucose-lowering effects. As this mainly has been observed in CVOTs in T2DM, further investigation in the adjunctive therapy for type 1 diabetes is suggested.