A new class of glucose-lowering therapy for type 2 diabetes: the latest development in the incretin arena

In 2005, the first GLP-1 receptor agonist was launched as a glucose-lowering treatment for people with type 2 diabetes. GLP-1 is a member of the incretin family, a set of hormones that are released from the gastrointestinal tract following the intake of nutrients, and it had been found to enhance insulin secretion in response to hyperglycaemia. 1 Viljoen A Bain SC Glucagon-like peptide 1 therapy: from discovery to type 2 diabetes and beyond. Endocrinol Metab. 2023; 38: 25-33 Crossref Scopus (2) Google Scholar GLP-1 receptor agonists reduced the postprandial rise in glucagon seen in people with type 2 diabetes, both in a glucose-dependent manner, meaning that hypoglycaemia was only seen when co-administered with insulin or insulin secretagogues. GLP-1 receptor agonists also cause weight reduction, initially attributed to slowing of gastric emptying and side-effects of nausea and vomiting, but which is mainly due to central satiety. Being a peptide, the administration of GLP-1 receptor agonists necessitated subcutaneous administration, which was initially twice daily with meals. However, various technological advances have led to the most frequently initiated agents being once-weekly preparations and there is also a co-formulation with a permeation enhancer, which allows for once-daily oral administration. 2 Chudleigh RA Platts J Bain SC Comparative effectiveness of long-acting GLP-1 receptor agonists in type 2 diabetes: a short review on the emerging data. Diabetes Metab Syndr Obes. 2020; 13: 433-438 Crossref PubMed Scopus (12) Google Scholar , 3 Husain M Birkenfeld AL Donsmark M et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2019; 381: 841-851 Crossref PubMed Scopus (843) Google Scholar Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USAIn people with type 2 diabetes, retatrutide showed clinically meaningful improvements in glycaemic control and robust reductions in bodyweight, with a safety profile consistent with GLP-1 receptor agonists and GIP and GLP-1 receptor agonists. These phase 2 data also informed dose selection for the phase 3 programme. Full-Text PDF