The most common cause of monogenic obesity is the presence of melanocortin-4 receptor (MC4R) gene variants and treating morbidly obese individuals with MC4R gene is extremely challenging. Research to filter an effective modality for these particular cases is progressing and as an add on to the existing ones, a recent data published in the ‘Journal of Clinical Research in Pediatric Endocrinology’ provide evidence to the significance of choosing effective treatment options for MC4R carriers.

      The study was conducted in an adolescent female patient admitted initially at the age of 12.5 years with a complaint of progressive weight gain. She had marked excess of appetite since infancy. On physical examination of the pubertal female patient with a body mass index of 36.1 kg/m2 there was no pathological finding except diffuse acanthosis nigricans. Laboratory examinations revealed only insulin resistance. Weight loss was not achieved with lifestyle changes, metformin and orlistat treatments. Genetic examinations had identified a sporadic heterozygous c.206T>G(p.I69R) variant in MC4R gene.

      Treatment with the GLP-1 RA, liraglutide, was initiated and a 19.2% reduction was achieved in the body weight and BMI at the end of 32 weeks. However, the patient, who could not tolerate the gastrointestinal side effects, was observed to gain weight when she stopped taking the drug for two weeks. After starting the drug at a dose of 1.8 mg/day, the weight gain stopped, but the patient decided to discontinue the drug and hesitated to appear for follow up visits after 43 weeks of treatment initiation. Telephonic contact with the patient revealed that she returned to her pre-treatment weight (145 kg) a few months after she discontinued the drug.

      Monogenic obesity should be considered in patients with early onset obesity and in whom appetite control cannot be achieved. Even with these positive results with liraglutide, the treatment could not be continued due to side effects. Hence the researchers urge that in cases like the one demonstrated in the study, there is a need for effective treatment options with tolerable side effects for effective long-term management.