Related Experiment Video
Updated: Sep 23, 2025
Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in Göttingen Minipigs and Landrace Pigs
Published on: April 17, 2021
Pleiotropic effects of SGLT2 inhibitors and heart failure outcomes
Panagiotis Theofilis1, Marios Sagris1, Evangelos Oikonomou2
11(st) Cardiology Department, Hippokration General Hospital, University of Athens Medical School, Athens, Greece.
Insights
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are revolutionizing heart failure (HF) treatment by offering pleiotropic benefits beyond diabetes management. These drugs reduce HF hospitalizations through mechanisms like improved autophagy and reduced inflammation, regardless of diabetes status.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Heart failure (HF) is a growing public health issue with complex causes like inflammation and fibrosis.
- Sodium-glucose cotransporter-2 (SGLT2) inhibitors, initially for type 2 diabetes, show significant promise in HF treatment.
Purpose of the Study:
- To review the historical development and current mechanistic understanding of SGLT2 inhibitors in HF.
- To explore the pleiotropic effects of SGLT2 inhibition on HF pathophysiology.
Main Methods:
- Review of experimental studies and clinical trial data on SGLT2 inhibitors in HF.
- Analysis of proposed mechanisms including autophagy, inflammation, oxidative stress, fibrosis, endothelial function, and epicardial adipose tissue.
Main Results:
- SGLT2 inhibitors demonstrate pleiotropic effects beneficial for HF, potentially restoring autophagy.
- Mechanisms include regulating inflammatory, oxidative, and fibrotic pathways, improving endothelial function, and reducing epicardial adipose tissue.
- Clinical trials show reduced HF hospitalizations with SGLT2 inhibitors, irrespective of diabetes status or ejection fraction.
Conclusions:
- SGLT2 inhibitors offer a novel therapeutic approach for HF, with benefits extending beyond glycemic control.
- Further clinical trials are anticipated to provide more evidence on the broad effects of SGLT2 inhibition across the spectrum of HF.
Abstract:
Heart failure (HF) represents a major public health concern with increasing prevalence among aging populations, with multifactorial pathophysiology including inflammation, oxidative stress, endothelial dysfunction, and fibrosis, among others. Lately, the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally destined for the treatment of type 2 diabetes mellitus, have revolutionized the treatment of HF. In this review article, we provide the milestones and the latest mechanistic evidence of SGLT2 inhibition in HF. Owing to the results of experimental studies, several pleiotropic effects of SGLT2 inhibitors have been proposed, including the restoration of autophagy which may be significant in the reversal of the aforementioned HF pathophysiology according to a latest hypotheses. Additional mechanisms consist of the regulation of inflammatory, oxidative, and fibrotic pathways, together with the improvement of endothelial function and reduction of epicardial adipose tissue. Other than their role as antidiabetic agents, a reduction in heart failure hospitalizations has been noted following their use in clinical trials, irrespective of DM status and degree of systolic dysfunction. Upcoming randomized trials are expected to additional clinical and mechanistic evidence regarding the diverse effects of SGLT2 inhibition across the spectrum of heart failure.
Related Concept Videos
01:30Heart Failure V: Medical Management
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:26Heart Failure Drugs: Inotropic Agents
01:22Heart Failure Drugs: Diuretics
01:29Heart Failure II: Pathophysiology
01:22Heart Failure Drugs: β-Blockers