ESPE Abstracts

Recent years have seen rapid changes in the availability of new medical treatments as an adjunct to lifestyle support for adults, children and adolescents living with obesity. Although the GLP1 receptor agonist (RA) liraglutide 3 mg, given by daily subcutaneous injection, has been available for some time, the recent approval of semaglutide 2.4 mg weekly represents a major advance in efficacy. In clinical trials, semaglutide results in weight loss of 15% or more in more than half the patients treated, and this is associated with improvements in a range of cardiovascular risk factors as well as quality of life. Adverse events of nausea tend to resolve over time with gradual dose titration. The MC4 receptor agonist, setmelanotide has also been approved for the treatment of some very rare genetic causes of obesity, specifically POMC deficiency, leptin receptor deficiency and Bardet-Beidl Syndrome; with these targeted therapies weight loss of 15% or more is to be expected and will become the treatment standard. In the future we may see even greater weight loss, as GLP1 RAs are combined with other gut hormone analogues; a combination drug that targets both GLP1 and GIP, tirzepatide, is already approved for treatment of adults with obesity; paediatric trials are ongoing. Others, such as the amylin analogue cagrilintide, and triple agonists that target GLP1, GIP and glucagon, such as retatrutide, are also looking promising. Currently, these effective treatments are given by daily or weekly injection, but recent data has shown that higher doses of semaglutide are effective when given orally together with an absorption enhancer, and several small molecule oral GLP1 RA are also in development. These rapid advances allow personalised medicine for the treatment of some rare causes of obesity, effective treatment for many others and are now approaching efficacy seen with surgical approaches.