Metreleptin (DB09046): A Comprehensive Monograph on a Recombinant Leptin Analog for the Treatment of Lipodystrophy Syndromes

Executive Summary

Metreleptin is a synthetic, recombinant analog of the human hormone leptin, engineered as a targeted replacement therapy for rare and severe metabolic disorders stemming from leptin deficiency.[1] Marketed under the brand names Myalept® and Myalepta®, it represents a significant therapeutic advance for patients with lipodystrophy syndromes, a group of diseases characterized by a pathological loss of adipose tissue and subsequent metabolic derangements.[3] Its primary approved indication is as an adjunct to diet for treating the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy (GL).[1]

The drug functions as a direct agonist of the human leptin receptor (ObR), mimicking the action of the absent endogenous hormone to restore critical metabolic signaling pathways.[6] Clinical evidence has robustly demonstrated its efficacy in improving glycemic control, reducing severe hypertriglyceridemia, and mitigating hepatic steatosis in patients with GL.[6] However, the therapeutic landscape is complex. Regulatory approvals differ globally, with agencies in the European Union and Canada extending the indication to include certain patients with partial lipodystrophy (PL), a distinction not made by the U.S. Food and Drug Administration (FDA).[3]