Approved & therapeutic
Metreleptin
Myalept
Metreleptin is a recombinant analog of human leptin, approved in the US as an adjunct to diet as replacement therapy for the complications of leptin deficiency in congenital or acquired generalized lipodystrophy. It carries a boxed warning for neutralizing anti-metreleptin antibodies and for lymphoma, and is available only through the restricted MYALEPT REMS program, which requires certified prescribers and certified pharmacies.
- Status
- Metreleptin is approved by the U.S. FDA and has official prescribing information.
- Evidence
- Approved labeling. Official prescribing information exists, based on clinical trials in people.
- Half-life
- 3.8 to 4.7 hours after subcutaneous dosing in healthy subjects. The label notes there are limited pharmacokinetic data in patients with generalized lipodystrophy, and that clearance is expected to be delayed if anti-metreleptin antibodies are present.
- How it's taken
- Subcutaneous injection once daily, after reconstitution of the lyophilized powder. Preservative-free sterile water for injection is recommended for neonates and infants.
- Mechanism
- Metabolic (non-incretin)
- Pathways
- Leptin
How Metreleptin works
Metreleptin binds and activates the human leptin receptor, a Class I cytokine receptor signaling through the JAK/STAT pathway. In people who lack functional adipose tissue and therefore lack leptin, replacing the hormone restores signals that reduce food intake and improve insulin sensitivity and lipid handling.
What research has looked at
- In the single-arm, open-label study supporting approval, mean HbA1c fell by about 2 percentage points from a baseline of 8.5 percent at 12 months, and mean fasting glucose fell by about 49 points on the mg/dL scale from a baseline of 174, in patients with generalized lipodystrophy.
- Median fasting triglycerides fell by about 55 percent at 12 months, from a median baseline of 348 on the mg/dL scale.
- Important limitation on both of the above: the study had no control group, and the label states that concomitant antihyperglycemic and lipid-altering medications were not held constant — some patients had insulin increased, others had large reductions or stopped it entirely. The changes therefore cannot be cleanly attributed to metreleptin.
- The label's Pharmacodynamics section states that clinical studies suggest metreleptin increases insulin sensitivity and reduces food intake; this is a mechanistic observation, not a measured trial endpoint.
- It is replacement therapy for a rare deficiency, not a general metabolic or weight-loss agent; the label explicitly excludes partial lipodystrophy, HIV-related lipodystrophy, liver disease including NASH, and metabolic disease without concurrent generalized lipodystrophy.
Evidence level: Approved labeling. Official prescribing information exists, based on clinical trials in people. These are areas studied or reported, not promised effects.
Reported side effects and risks
- Boxed warning: anti-metreleptin antibodies with neutralizing activity have been identified and could inhibit endogenous leptin action and cause loss of efficacy; severe infection and worsening metabolic control have been reported.
- Boxed warning: T-cell lymphoma has been reported in patients with acquired generalized lipodystrophy, both treated and not treated with metreleptin; the product is available only through the restricted MYALEPT REMS Program, which requires certified prescribers and certified pharmacies.
- Contraindicated in general obesity not associated with congenital leptin deficiency.
- Contraindicated in patients with prior severe hypersensitivity reactions to metreleptin or to any of the product components; reported reactions have included anaphylaxis, urticaria and generalized rash.
- Do not stop or reduce metreleptin on your own. In patients with a history of pancreatitis or severe hypertriglyceridemia, the label requires a physician-supervised taper when discontinuing, with triglyceride monitoring and possible adjustment of lipid-lowering medication. Pancreatitis occurred in 2 of 48 patients (4 percent) in the pivotal study, both with a prior history of it.
- Hypoglycemia in patients also taking insulin or insulin secretagogues such as sulfonylureas; requirements can fall substantially and blood glucose must be closely monitored.
- Autoimmunity: progression of autoimmune hepatitis and of membranoproliferative glomerulonephritis (with massive proteinuria and renal failure) has been observed in some patients with acquired generalized lipodystrophy; causality is not established.
- Hypersensitivity reactions including anaphylaxis, urticaria and generalized rash.
- Most common reactions (at least 10 percent) were headache, hypoglycemia, decreased weight and abdominal pain.
- Benzyl alcohol toxicity: the product contains benzyl alcohol when reconstituted with bacteriostatic water, which has been associated with serious adverse events and death in neonates and premature infants; preservative-free sterile water is recommended for neonates and infants.
Sources
- PubMed research on Metreleptin · NIH · National Library of Medicine
- DrugBank record for Metreleptin · DrugBank
- Active clinical trials for Metreleptin · U.S. National Library of Medicine
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Metreleptin FAQ
What is Metreleptin?
Metreleptin is a recombinant analog of human leptin, approved in the US as an adjunct to diet as replacement therapy for the complications of leptin deficiency in congenital or acquired generalized lipodystrophy. It carries a boxed warning for neutralizing anti-metreleptin antibodies and for lymphoma, and is available only through the restricted MYALEPT REMS program, which requires certified prescribers and certified pharmacies.
How does Metreleptin work?
Metreleptin binds and activates the human leptin receptor, a Class I cytokine receptor signaling through the JAK/STAT pathway. In people who lack functional adipose tissue and therefore lack leptin, replacing the hormone restores signals that reduce food intake and improve insulin sensitivity and lipid handling.
Is Metreleptin FDA approved?
Yes. Metreleptin is approved by the U.S. FDA and has official prescribing information. Evidence level: approved labeling. Official prescribing information exists, based on clinical trials in people.
What is the half-life of Metreleptin?
Reported half-life: 3.8 to 4.7 hours after subcutaneous dosing in healthy subjects. The label notes there are limited pharmacokinetic data in patients with generalized lipodystrophy, and that clearance is expected to be delayed if anti-metreleptin antibodies are present.
How is Metreleptin taken?
Subcutaneous injection once daily, after reconstitution of the lyophilized powder. Preservative-free sterile water for injection is recommended for neonates and infants.
What side effects have been reported with Metreleptin?
Reported in the sources: Boxed warning: anti-metreleptin antibodies with neutralizing activity have been identified and could inhibit endogenous leptin action and cause loss of efficacy; severe infection and worsening metabolic control have been reported; Boxed warning: T-cell lymphoma has been reported in patients with acquired generalized lipodystrophy, both treated and not treated with metreleptin; the product is available only through the restricted MYALEPT REMS Program, which requires certified prescribers and certified pharmacies; Contraindicated in general obesity not associated with congenital leptin deficiency; Contraindicated in patients with prior severe hypersensitivity reactions to metreleptin or to any of the product components; reported reactions have included anaphylaxis, urticaria and generalized rash; Do not stop or reduce metreleptin on your own. In patients with a history of pancreatitis or severe hypertriglyceridemia, the label requires a physician-supervised taper when discontinuing, with triglyceride monitoring and possible adjustment of lipid-lowering medication. Pancreatitis occurred in 2 of 48 patients (4 percent) in the pivotal study, both with a prior history of it; Hypoglycemia in patients also taking insulin or insulin secretagogues such as sulfonylureas; requirements can fall substantially and blood glucose must be closely monitored; Autoimmunity: progression of autoimmune hepatitis and of membranoproliferative glomerulonephritis (with massive proteinuria and renal failure) has been observed in some patients with acquired generalized lipodystrophy; causality is not established; Hypersensitivity reactions including anaphylaxis, urticaria and generalized rash; Most common reactions (at least 10 percent) were headache, hypoglycemia, decreased weight and abdominal pain; Benzyl alcohol toxicity: the product contains benzyl alcohol when reconstituted with bacteriostatic water, which has been associated with serious adverse events and death in neonates and premature infants; preservative-free sterile water is recommended for neonates and infants.
Educational summary compiled from the sources listed above. Not medical advice. Peptide Vault does not sell, source or recommend any compound. Talk to a qualified clinician before starting or changing anything.