Recombinant methionyl human leptin or
metreleptin is a synthetic
leptin analog that has been trialed in patients with
leptin-deficient conditions, such as
leptin deficiency due to mutations in the
leptin gene, hypothalamic
amenorrhea, and
lipodystrophy syndromes. These syndromes are characterized by partial or complete absence of adipose tissue and
hormones derived from adipose tissue, most importantly
leptin. Patients deficient in
leptin exhibit a number of severe metabolic abnormalities such as
hyperglycemia,
hypertriglyceridemia, and hepatic steatosis, which can progress to
diabetes mellitus,
acute pancreatitis, and
hepatic cirrhosis, respectively. For the management of these
abnormalities, multiple therapies are usually required, and advanced stages may be progressively difficult to treat. Following many successful trials, the US Food and Drug Administration approved
metreleptin for the treatment of non-HIV-related forms of
generalized lipodystrophy.
Leptin replacement
therapy with
metreleptin has, in many cases, reversed these metabolic complications, with improvements in
glucose-
insulin-
lipid homeostasis, and regression of
fatty liver disease. Besides being effective, a daily subcutaneous administration of
metreleptin is generally safe, but the causal association between
metreleptin and immune complications (such as
lymphoma) is still unclear. Moreover, further investigation is needed to elucidate mechanisms by which
metreleptin leads to the development of anti-
leptin antibodies. Herein, we review clinical aspects of
generalized lipodystrophy and the pharmacological profile of
metreleptin. Further, we examine studies that assessed the safety and efficacy of
metreleptin, and outline some clinical perspectives on the
drug.