Mechanistic insights regarding the role of SGLT2 inhibitors and GLP1 agonist drugs on cardiovascular disease in diabetes

Prog Cardiovasc Dis. 2019 Jul-Aug;62(4):349-357. doi: 10.1016/j.pcad.2019.07.005. Epub 2019 Aug 2.

Abstract

The treatment landscape for patients with established or at high risk for cardiovascular disease and type 2 diabetes mellitus has entirely changed over the past decade, with the introduction of several anti-hyperglycemic agents. Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) agonists are two anti-hyperglycemic classes which have been of special interest after multiple large cardiovascular disease (CVD) outcomes studies have demonstrated superiority of these agents compared to placebo for major adverse CVD events and in some cases, hospitalization for heart failure. Despite the dramatic results of these trials, only recently have we began to understand the mechanisms underlying these CVD benefits. Here we review the underlying mechanisms which have the greatest plausibility for both of these agents including the impact of ventricular loading conditions, direct effects on cardiac structure and function, myocardial energetics and sodium/hydrogen exchange for SGLT2 inhibitors, and the anti-atherosclerotic, anti-inflammatory, and modulation of endothelial function for GLP-1 agonists.

Keywords: Cardiovascular mechanisms; Cardiovascular outcomes; GLP-1 agonists; SGLT2-inhibitors.

Publication types

  • Review

MeSH terms

  • Aged
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / physiopathology
  • Cardiovascular Diseases / prevention & control*
  • Cardiovascular System / drug effects
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Female
  • Follow-Up Studies
  • Glucagon-Like Peptide 1 / administration & dosage*
  • Glucagon-Like Peptide 1 / antagonists & inhibitors*
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Middle Aged
  • Prevalence
  • Risk Assessment
  • Severity of Illness Index
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*

Substances

  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors
  • Glucagon-Like Peptide 1