Sodium glucose cotransporter 2 inhibitors: mechanisms of action in heart failure

Abstract

Diabetes is a key independent risk factor in the development of heart failure (HF) and a strong, adverse prognostic factor in HF patients. HF remains the primary cause of hospitalisation for diabetics and, as previous studies have shown, when HF occurs in these patients, intensive glycaemic control does not directly improve the prognosis. Recent clinical studies assessing a new class of antidiabetic drugs, sodium-glucose cotransporter 2 inhibitors (SGLT2is) showed some unexpected beneficial results. Patients treated with SGLT2is had a significant decrease in both cardiovascular (CV) and all-cause mortality and less hospitalisations due to HF compared to those given a placebo. These significant clinical benefits occurred quickly after the drugs were administered and were not solely due to improved glycaemic control. These groundbreaking clinical trials’ results have already changed clinical practice in the management of patients with diabetes at high CV risk. These trials have triggered numerous experimental studies aimed at explaining the mechanisms of action of this unique group of drugs. This article presents the current state of knowledge about the mechanisms of action of SGLT2is developed for the treatment of diabetes and which, thanks to their cardioprotective effects, may, in the future, become a treatment for patients with HF.

Shen-Yuan-Dan Capsule Attenuates Verapamil-Induced Zebrafish Heart Failure and Exerts Antiapoptotic and Anti-Inflammatory Effects via Reactive Oxygen Species–Induced NF-κB Pathway

“…Activating Caspase-1 can induce the release of the level of IL-1β and IL-18. IL-18 can promote the production of TNF-α, while TNF-α reacts to Caspase-1, thus forming an inflammation reaction waterfall, promoting cell death, and eventually leading to HF (Mieczysław et al, 2020). In the present study, we also demonstrated that SYDC could inhibit apoptosis by downregulating the mRNA expressions of Bax, Caspase-3, and Caspase-1 and upregulating the mRNA expressions of Bcl-2 in the verapamil-treated larval zebrafish model.…”

“…ROS-mediated nuclear factor-kappa B (NF-κB) signaling pathway is an emerging inflammatory and apoptosis signaling pathway (Sahar et al, 2020). Accumulation of ROS leads to the activation of NF-κB, which is the basic transcription factor that activates inflammation (Mieczysław et al, 2020). Prolonged activation of NF-κB causes the release of both a large number of proinflammatory cytokines and an intensification of cardiomyocyte apoptosis (Mieczysław et al, 2020).…”

An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors

“…During this lack of oxygen, ketone bodies can be better substrates than FAs at producing ATP due to a more favorable P/O ratio (2.50). Ketone bodies are also better than glucose, even though their P/O values are not significantly different [ 155 , 208 , 209 ]. β-HB must be converted into acetoacetate to generate energy.…”

Therapie des Typ-2-Diabetes

“…Die zugrunde liegenden Mechanismen der kardialen und renalen Protektion von SGLT2-Hemmern sind Gegenstand umfangreicher Studien [138][139][140][141][142].…”