Bridging the gap between GLP1-receptor agonists and cardiovascular outcomes: evidence for the role of tirzepatide

Cardiovasc Diabetol. 2024 Jul 10;23(1):242. doi: 10.1186/s12933-024-02319-7.

Abstract

Tirzepatide is a new drug targeting glucagon-like peptide 1(GLP1) and gastric inhibitory polypeptide (GIP) receptors. This drug has demonstrated great potential in improving the clinical outcomes of patients with type 2 diabetes. It can lead to weight loss, better glycemic control, and reduced cardiometabolic risk factors. GLP1 receptor agonists have been proven effective antidiabetic medications with possible cardiovascular benefits. Even though they have been proven to reduce the risk of major adverse cardiovascular events, their effectiveness in treating heart failure is unknown. Unlike traditional GLP1 receptor agonists, tirzepatide is more selective for the GIP receptor, resulting in a more balanced activation of these receptors. This review article discusses the possible mechanisms tirzepatide may use to improve cardiovascular health. That includes the anti-inflammatory effect, the ability to reduce cell death and promote autophagy, and also its indirect effects through blood pressure, obesity, and glucose/lipid metabolism. Additionally, tirzepatide may benefit atherosclerosis and lower the risk of major adverse cardiac events. Currently, clinical trials are underway to evaluate the safety and efficacy of tirzepatide in patients with heart failure. Overall, tirzepatide's dual agonism of GLP1 and GIP receptors appears to provide encouraging cardiovascular benefits beyond glycemic control, offering a potential new therapeutic option for treating cardiovascular diseases and heart failure.

Keywords: GIP receptor; GLP-1 receptor; GLP1 receptor agonists; Heart failure; Tirzepatide.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / therapeutic use
  • Biomarkers / blood
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Cardiovascular Diseases* / drug therapy
  • Cardiovascular Diseases* / prevention & control
  • Cardiovascular System / drug effects
  • Cardiovascular System / metabolism
  • Cardiovascular System / physiopathology
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / drug therapy
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide-1 Receptor Agonists*
  • Glucagon-Like Peptide-1 Receptor* / metabolism
  • Glucagon-Like Peptide-2 Receptor
  • Humans
  • Hypoglycemic Agents* / adverse effects
  • Hypoglycemic Agents* / pharmacology
  • Hypoglycemic Agents* / therapeutic use
  • Incretins* / adverse effects
  • Incretins* / therapeutic use
  • Receptors, Gastrointestinal Hormone / agonists
  • Receptors, Gastrointestinal Hormone / metabolism
  • Risk Assessment
  • Signal Transduction / drug effects
  • Tirzepatide
  • Treatment Outcome

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Tirzepatide
  • GLP1R protein, human
  • Incretins
  • Receptors, Gastrointestinal Hormone
  • gastric inhibitory polypeptide receptor
  • Blood Glucose
  • Anti-Inflammatory Agents
  • Biomarkers
  • Glucagon-Like Peptide-2 Receptor
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide-1 Receptor Agonists