Successful naltrexone-bupropion treatment after several treatment failures in a patient with severe monogenic obesity

We describe the therapeutic journey of a 33-year-old patient with early-onset obesity (BMI 56.7 kg/m²) and hyperphagia due to a likely pathogenic heterozygous melanocortin-4 receptor (MC4R) gene variant. She was unsuccessfully treated with several intensive lifestyle interventions, gastric bypass surgery (−40 kg weight loss, followed by +39.8 kg weight regain), liraglutide 3 mg (−3.8% weight loss with sustained hyperphagia), and metformin treatment. However, naltrexone-bupropion treatment led to −48.9 kg (−26.7%) weight loss, of which −39.9 kg (−38.3%) was fat mass, in 17 months of treatment. Importantly, she reported improved hyperphagia and quality of life. We describe the potential beneficial effects of naltrexone-bupropion on weight, hyperphagia, and quality of life in a patient with genetic obesity. This extensive journey shows that various anti-obesity agents can be initiated, subsequently terminated when ineffective and substituted with other anti-obesity agents to identify the most efficient anti-obesity treatment.