Metreleptine

Metreleptin is a recombinant analog of the human hormone leptin used as replacement therapy for leptin deficiency, most notably in people with generalized lipodystrophy. Leptin is a hormone involved in regulating energy balance, appetite, and lipid and glucose metabolism. By acting as a leptin receptor agonist, metreleptin aims to restore leptin signaling that is absent or severely reduced in lipodystrophy, with the goal of improving metabolic complications.

Clinical use centers on leptin deficiency due to congenital or acquired generalized lipodystrophy, and it has been used in selected patients with partial lipodystrophy under specialist supervision. Metreleptin is administered by subcutaneous injection, typically administered daily, with dosing and duration tailored to the individual and monitored for efficacy and safety.

In treated patients, metreleptin can improve several metabolic parameters, including triglyceride levels, hepatic steatosis, insulin sensitivity, and glycemic control. Weight effects are variable and do not replace the need for comprehensive metabolic management.

Safety considerations include common adverse events such as injection-site reactions, nausea, abdominal discomfort, and headache. There have been reports of anti-leptin antibody formation and, in some cases, serious immune- or lymphoid-related adverse events. Regulatory agencies have issued safety communications and require careful patient selection and monitoring, given concerns about rare but potential malignancies in certain lipodystrophy populations. Metreleptin remains a targeted therapy for leptin deficiency in specific lipodystrophy syndromes, with ongoing evaluation of its long-term safety and efficacy.