A Case of Paradoxical Appetite Increase During Semaglutide Therapy

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is widely used to reduce appetite and promote weight loss in patients with type 2 diabetes. However, individual variability may lead to paradoxical responses. We describe a 60-year-old woman with type 2 diabetes who experienced progressive weight gain and increased appetite during 12 months of semaglutide therapy, despite previous successful weight loss with sodium-glucose cotransporter 2 (SGLT2) inhibitors. Her body mass index (BMI) rose from 31.6 to 34.6 kg/m2, accompanied by worsening glycemic control. Eating behavior assessment with the Dutch Eating Behavior Questionnaire revealed a maximum score for emotional eating, suggesting a strong psychological barrier to treatment efficacy. Genetic factors, such as GLP-1 receptor polymorphisms, may also contribute to reduced responsiveness. This case highlights the possible influence of both emotional and genetic factors on treatment outcomes and emphasizes the need for personalized approaches in the management of obesity and type 2 diabetes.