Glucagon-like-peptide-1 receptor agonists and the management of type 2 diabetes-backwards and forwards.

This editorial is stimulated by the article by Alqifari et al published in the World Journal of Diabetes (2024). Alqifari et al focus on practical advice for the clinical use of glucagon-like-peptide-1 (GLP-1) receptor agonists (GLP-1RAs) in the management of type 2 diabetes and this editorial provides complementary information. We initially give a brief historical perspective of the development of GLP-1RAs stimulated by recognition of the 'incretin effect', the substantially greater insulin increase to enteral when compared to euglycaemic intravenous glucose, and the identification of the incretin hormones, GIP and GLP-1. In addition to stimulating insulin, GLP-1 reduces postprandial glucose levels by slowing gastric emptying. GLP-1RAs were developed because native GLP-1 has a very short plasma half-life. The majority of current GLP-1RAs are administered by subcutaneous injection once a week. They are potent in glucose lowering without leading to hypoglycaemia, stimulate weight loss in obese individuals and lead to cardiovascular and renal protection. The landscape in relation to GLP-1RAs is broadening rapidly, with different formulations and their combination with other peptides to facilitate both glucose lowering and weight loss. There is a need for more information relating to the effects of GLP-1RAs to induce gastrointestinal symptoms and slow gastric emptying which is likely to allow their use to become more effective and personalised.