Metreleptin

Summary

Metreleptin is a recombinant analog of human leptin approved for treatment of the metabolic complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy. It is administered subcutaneously and replaces deficient endogenous leptin to correct severe hypertriglyceridemia, hyperglycemia, and hepatic steatosis associated with lipodystrophy syndromes.

Mechanism of Action

Binds to and activates the leptin receptor (OB-R), a member of the cytokine receptor superfamily, thereby restoring leptin signaling in leptin-deficient states. Regulates energy homeostasis, appetite suppression, and metabolic function through hypothalamic pathways, and modulates insulin sensitivity and lipid metabolism.

Routes of Administration

Goals & Uses

• Improvement of hyperglycemia and insulin resistanceMetabolic / EndocrineHigh
• Treatment of partial lipodystrophy metabolic complicationsMetabolicLow
• Neuroendocrine restoration in hypothalamic amenorrheaReproductive EndocrinologyLow
• Reduction of hypertriglyceridemia in lipodystrophyMetabolicHigh
• Reduction of hepatic steatosisMetabolicModerate
• Appetite and weight regulation in leptin deficiencyWeight ManagementModerate

Contraindications

• General obesity without lipodystrophyOff Label Use RiskHigh
• Known hypersensitivity to metreleptin or excipientsAllergy / ImmunologicHigh

Adverse Effects

• HypoglycemiaMetabolicCommonAbnormally low blood glucose
• Injection site reactionsLocalCommon
• HeadacheNeurologicCommonPain in the head or upper neck
• Anti-metreleptin antibodies with neutralizing activityImmunologicUncommon
• Abdominal pain / nauseaGastrointestinalUncommon
• LymphomaOncologyRare

Drug Interactions

• InsulinModerateMay increase risk of low blood sugar
• Oral antidiabetic agents (e.g., sulfonylureas)Moderate
• Warfarin and other narrow therapeutic index drugs metabolized by CYP450Low

Population Constraints

• PregnancyReproductive SafetyRelative
• Renal impairmentOrgan ImpairmentRelative
• Pediatric patients < 2 yearsAgeRelative
• Patients with history of lymphomaOncologicRelative

Regulatory Status

• European UnionApprovedApproved: Treatment of leptin deficiency in patients with congenital or acquired generalized lipodystrophy in adults and children aged 2 years and aboveApproved by EMA in 2018 under brand name Myalepta; orphan medicinal product designation.
• United StatesApprovedApproved: Treatment of the complications of leptin deficiency in adults and children with congenital or acquired generalized lipodystrophyApproved by FDA February 2014 (Myalept); subject to REMS due to lymphoma and anti-drug antibody risks. Orphan drug designation.
• United KingdomApprovedApproved: Treatment of leptin deficiency in patients with congenital or acquired generalized lipodystrophy aged 2 years and aboveApproved post-Brexit under Myalepta brand; MHRA authorization maintained following EU approval precedent.

Approved by FDA in February 2014 under the brand name Myalept for generalized lipodystrophy; approved in Japan in 2013. In the EU, approved by EMA in 2018 under the brand name Myalepta. Carries a REMS program in the US due to risk of anti-metreleptin antibodies with neutralizing activity and potential for lymphoma.

Evidence & Sources

No sources recorded yet.