Add-on value of tirzepatide versus semaglutide

Type 2 diabetes is a complex disease with several key defects, including impaired insulin secretion, increased glucagon secretion, and insulin resistance, which is exacerbated by obesity. Thus, besides lifestyle measures, pharmacological therapy should aim to target most, if not all, of these anomalies. To reach this goal, combining drugs with different complementary modes of action is commonly used in clinical practice. Receptor agonists of GLP-1, a well known incretin hormone, tackle several of these defects in type 2 diabetes. 1 Nauck MA Quast DR Wefers J Meier JJ GLP-1 receptor agonists in the treatment of type 2 diabetes—state-of-the-art. Mol Metab. 2021; 46101102 Crossref PubMed Scopus (157) Google Scholar By potentiating insulin secretion in response to glucose and inhibiting glucagon secretion, they are among the most powerful agents to improve glucose control without inducing hypoglycaemia. In addition, compared with other glucose-lowering drugs, GLP-1 receptor agonists are associated with the greatest weight loss, which could contribute to reducing insulin resistance. Furthermore, these drugs have proven their ability to reduce the risk of major cardiovascular adverse events in patients with type 2 diabetes at high cardiovascular risk. 1 Nauck MA Quast DR Wefers J Meier JJ GLP-1 receptor agonists in the treatment of type 2 diabetes—state-of-the-art. Mol Metab. 2021; 46101102 Crossref PubMed Scopus (157) Google Scholar Overall, GLP-1 receptor agonists are regarded as crucial in the most recent international guidelines for the management of type 2 diabetes, especially in patients with atherosclerotic cardiovascular disease or obesity. 2 Draznin B Aroda VR Bakris G et al. 9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes—2022. Diabetes Care. 2022; 45: S125-S143 PubMed Google Scholar Effects of subcutaneous tirzepatide versus placebo or semaglutide on pancreatic islet function and insulin sensitivity in adults with type 2 diabetes: a multicentre, randomised, double-blind, parallel-arm, phase 1 clinical trialThe glycaemic efficacy of GIP/GLP-1 receptor agonist tirzepatide in type 2 diabetes results from concurrent improvements in key components of diabetes pathophysiology, namely β-cell function, insulin sensitivity, and glucagon secretion. These effects were large and help to explain the remarkable glucose-lowering ability of tirzepatide seen in phase 3 studies. Full-Text PDF