SGLT-2 Inhibitors in Heart Failure and Type-2 Diabetes: Hitting Two Birds with One Stone?

Abstract

Type 2 diabetes mellitus (T2DM) and heart failure (HF) have a tremendous impact worldwide, markedly reducing life-expectancy and quality of life. It is now known that each disease represents a risk factor for the other. Moreover, when they are combined, the prognosis is significantly worse. Until recently, these pathologies have been managed independently. However, their treatment paradigm is rapidly changing, with recent cardiovascular outcome trials showing that sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are effective in the management of both diseases. This article explores the interactions between T2DM and HF and the concept of diabetic cardiomyopathy and summarizes recent data regarding the effects of SGLT-2i on HF hospitalization and the proposed pathophysiological mechanisms involved. sively "glucocentric approach," T2DM management should rather contemplate the use of strategies that can reduce the risk of cardiovascular (and renal) events, including these new drugs and integrated control of all cardiovascular risk factors.This article aims to review the interaction between T2DM and HF and the concept of diabetic cardiomyopathy and to summarize recent data regarding the effects of SGLT-2i on HF hospitalization (HHF) and the proposed pathophysiological mechanisms involved.

Repurposing Antidiabetic Drugs for Cardiovascular Disease

“…SGLT2i act on the renal proximal tube to block the reabsorption of glucose. By this mechanism, the drugs lead to increased urinary glucose excretion, reduced blood glucose levels, and reduction of plasma volume and sodium load (Verma, 2019;Santos-Ferreira et al, 2020). Unexpectedly, SGLT2i induced a 35-40% risk reduction in cardiovascular death in patients already receiving optimal secondary prevention strategies for heart disease ( Table 1).…”

Expect the Unexpected: SGLT-2 Inhibitors in the Treatment of Type 2 Diabetes and/or Heart Failure

“…In the review, Santos-Ferreira et al [1] discuss different aspects of the association between two frequent comorbidities, type 2 diabetes (T2D) and heart failure (HF). There is an abundance of data suggesting that patients with T2D and HF have an increased risk of cardiovascular (CV) and all-cause mortality, as well as reduced quality of life [2,3].…”

“…The results from the studies with sodium-glucose cotransporter 2 (SGLT2) inhibitors -a novel class of agents that inhibit glucose reabsorption in the proximal renal tubule [4] -yielded the greatest surprise. These agents are the main focus of the review article by Santos-Ferreira et al [1], where three completed large CV outcome trials investigating SGLT2 inhibitors in patients with T2D and established atherosclerotic CV disease or multiple risk factors were elaborated in detail. The first one of these studies, EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), investigated the effects of empagliflozin on CV outcomes in patients with T2D and established atherosclerotic disease [5] and found a 35% relative risk reduction in the exploratory endpoint of HF hospitalization.…”

“…As noted in the review [1], the data from all these trials with SGLT2 inhibitors have changed the current understanding of the treatment paradigms of T2D and CV diseases, and HF in particular. Empagliflozin, as first-inclass SGLT2 inhibitor to demonstrate the beneficial effect on HF hospitalization, was recommended in the 2016 ESC guidelines for the diagnosis and treatment of HF [12] and Guidelines for CV prevention [13], for HF onset delay among patients with T2D.…”

“…In conclusion, the review "SGLT 2 Inhibitors in Heart Failure and Type 2 Diabetes: Hitting Two Birds with One Stone?" [1] provides relevant and accurate overview of existing data on SGLT2 inhibitors as novel class of glucose-lowering agents with convincing evidence in the prevention of HF in patients with T2D. Current guidelines for the treatment of T2D suggest that SGLT2 inhibitors should be used as second-line agents for glucose reduction and CV protection, after metformin.…”