Q. Can you tell us more about the effects of leptin on anorexic patients? An older teen patient skips meals, picks at her food, and exercises excessively. As a result, she has a daily caloric intake of less than 450 kcal. We have tried many approaches, but none seem to make a difference. I’ve heard that human recombinant leptin (metreleptin) treatment might help. Can you comment on this? (A. H., Oklahoma City)
A. Leptin has been known to impact eating and weight for some time. Recently, results of an off-label trial showed that metreleptin (Myalept®) had helpful effects in a case of a teen with AN. German and Swiss researchers led by Dr. Gertraud Gradl-Dietsch had very promising results when they treated the 15-year-old patient with an off-label test of metreleptin. The girl, who had a number of complaints and had been hospitalized at various times, had restrictive-type AN and a body mass index (BMI) of 16.3 kg/m2 when first seen. At home she skipped meals and picked at her food and had a self-reported caloric intake of less than 500 kcal per day. She was amenorrheic, exercised excessively, and had nighttime bradycardia (38-44 beats/minute). She reported feeling cold, tired, weak, irritable, and was depressed and had suicidal ideation (Obes Facts. 2023. 16:99).
She and her parents agreed to try off-label treatment with metreleptin for 9 days. The dosage on the first day of treatment was determined by measuring the patient’s serum leptin level (1:16 ng/ml). Daily dosages were 3.0-5.8 mg/day, given subcutaneously at 9 am. The patient self-assessed depressive and eating-disorder symptoms using the German version of the Beck Depression Inventory and the Eating Disorders Inventory. She was asked to choose the symptom that bothered her the most, and she decided at the end of the dosing period to work to increase the number of foods she was eating. Weekly phone calls also let her name the new food she was adding to her diet. A follow-up was done 175 days after completion of the 9-day dosing period.
Results of treatment with metreleptin were quickly seen. Within 2 days of starting treatment, the patient’s self-reported inner tension and depressed mood decreased. By the fourth day, the patient’s BDI-II score was cut in in half; her sleep improved, and her social interactions increased. She reported having many fewer mood swings and was less likely to harm herself. Her appetite varied widely during the dosing period. Her hunger, which had been rated as between 1.5 and 4.5 before dosing, now reached a peak value of 9 on dosing days 6 and 9, then fell to 1 on three days of the post-dosing period. Her urge to vomit was markedly reduced during dosing and increased afterward; binge eating was infrequent. She stopped cutting her food into tiny pieces and ate bread again for the first time in a year. She was also able “to imagine eating once-forbidden foods.”
At the final follow-up, the patient had gained almost 20 kg. She reported having a stable mood and her menses returned 3 months after treatment stopped. Her leptin levels were in a low-normal range. After 6 months, the teen had gained 15 kg.
The authors hypothesized that metreleptin impacts hunger and appetite. The case report suggests that mood was improved as well. Perhaps most interesting Ed thoughts diminished rapidly after starting metreleptin.
Metreleptin is a drug with significant side effects that have led to a specific side effect monitoring regime (Risk Evaluation and Mitigation Strategy, or REMS), and its use is still experimental for people with AN. The authors also correctly note that that randomized controlled studies are needed to better define the role of leptin and metreleptin in hunger and appetite.