ESPE Abstracts

Introduction: Congenital leptin deficiency can be treated with the human leptin analogon metreleptin as first reported in 1999. To date, the long-term effects (> 1 year) of metreleptin treatment on anthropometry and comorbidities have only been described in 8 patients with leptin deficiency. Here, we present the long-term effects of metreleptin substitution on weight and comorbidities in a patient with bioinactive leptin.

Methods: We retrospectively analyzed the effects of seven years of metreleptin treatment on body weight and comorbidities in a female patient with bioinactive leptin caused by biallelic variants in the leptin gene (c.309C>A, p.Asn103Lys).

Results: At initiation of metreleptin therapy, the 9-year old girl had severe obesity (39.3 kg/m², BMI SDS 3.5), hyperphagia and several comorbidities such as dyslipidemia, hyperinsulinemia, steatosis hepatis and sleep apnea syndrome. Metreleptin therapy was started with the recommended dose of 0.03 mg/kg lean body weight, was well tolerated, and resulted in controlled eating behaviour and reduced energy intake within few days. BMI decreased by -6.98 kg/m² in the first year of treatment, but increased to 37.8 kg/m² in the second year and remained constant in the following three years. Periods in which the uncontrolled eating behaviour recurred were not associated with the presence of neutralizing antibodies to metreleptin but with low adherence to daily injections. Increasing metreleptin dose to overcome the recurrence of uncontrolled eating behaviour had little or no effects on weight. Similar BMI reductions as in the first year occurred again in the fifth (∆BMIT4-T5: -6.83 kg/m²) and seventh year of treatment (∆BMIT6-T7: -5.48 kg/m²) and were attributed to periods when the patient changed her lifestyle toward a healthy diet, more physical activity and a strictly structured daily routine, resulting in high treatment compliance. To date, the 16-year old patient is still obese with a BMI of 31.4 kg/m² (BMI SDS 2.35), but her eating behaviour is well controlled and her metabolic comorbidities have almost disappeared.

Conclusion: This case report adds new data to the long-term efficacy and safety of metreleptin therapy in patients with leptin deficiency. Metreleptin reduced efficiently hyperphagia, metabolic comorbidities and weight as previously reported in the literature. While periods of low treatment adherence were associated with recurrence of symptoms, high treatment compliance, a healthy diet and sufficient exercise resulted in significant weight loss. Patients should be motivated to follow these treatment advices to maximize the benefits on anthropometry and health of metreleptin therapy.