Endocrine Abstracts

Introduction: It is estimated that around 5% of patients with severe (BMI >40kg/m²) and early onset obesity will have a monogenic cause, commonly within the leptin-melanocortin pathway. Treatment with Setmelanotide is available for POMC or LEPR deficiency only, whereas NHS testing for severe early onset obesity comprises a panel of 33 genes. Society for Endocrinology Guidelines recommend patients with “proven genetic cause of obesity and not eligible for Setmelanotide” should be prioritised for GLP-1 treatment.

Methods: We retrospectively analysed patients within the Somerset Weight management service, with a proven genetic cause of obesity treated with Semaglutide between January 2024 and August 2025.

Results: 181 patients were treated with Semaglutide, 12 with a genetic variant (GV) known to cause obesity and 169 with no genetic variant or weren’t tested (NGV). Baseline characteristics for the GV and NGV respectively were: 63.6%, 66.8% female, mean age: 35.5 (SD 11.4), 52.5 (SD 14.3), mean weight: 146.4kg (SD 39.3kg), 142.0kg (SD 34.7kg) and mean BMI: 50.3kg/m² (SD 11), 50.2 kg/m² (SD 10.5kg/m²). Within the GV group 11 and 9 patients had 6 month and 12 data, with mean weight loss of 9.1% (SD 3.9%) and 12.2% (SD 4.6%) respectively. In the NGV group 104/169 had 6 month data and 54/169 12 months data with mean weight loss of 9.5% (SD5.5%) and 13.7% (SD 6.6%) respectively. No patients in the GV group stopped due to side effects and 8.3% stopped within the first 6 months in the NGV group.

Discussion: We have shown that individuals with a genetic variation that is associated with obesity achieve similar weight loss with semaglutide to those without a known genetic variant and is extremely well tolerated. Genetic testing is unlikely to be necessary if an individual meets other criteria for prescribing GLP-1 medication on the NHS.