Head to head
Metreleptin against Leptin
The hormone and its recombinant form. The important number is not how much weight either produces but in whom: replacement transforms people who make almost no leptin and does close to nothing in ordinary obesity, which a 127 person randomised trial in 1999 already showed.
Column A
MetreleptinMetreleptin (Myalept), recombinant human leptin analogue
Transformative in people who make almost no leptin, and useless for ordinary obesity. The clearest case on this site of a hormone that only works as replacement.
Column B
LeptinLeptin (with metreleptin, Myalept, the approved recombinant analogue)
The fat-derived hormone that tells the brain how much energy is stored. Replacing it transforms the rare people who lack it; in common obesity a 127-person randomised trial in 1999 found small dose-dependent weight loss and no drug came of it. Metreleptin is approved for generalised lipodystrophy with a boxed warning.
Side by side, on the facts we can check
| Attribute | Metreleptin | Leptin |
|---|---|---|
| Category | Hormone | Metabolic |
| FDA status | FDA-approved as Myalept for complications of leptin deficiency in generalised lipodystrophy. Carries a boxed warning for anti-metreleptin antibodies with neutralising activity and for T-cell lymphoma risk, and is subject to a restricted distribution programme. Not approved for obesity or partial lipodystrophy. | Metreleptin (Myalept) FDA-approved 24 February 2014 (BLA 125390, Chiesi) as an adjunct to diet for complications of leptin deficiency in congenital or acquired generalised lipodystrophy; Drugs@FDA marketing status Prescription on 11 September 2026. Boxed warning for neutralising anti-metreleptin antibodies and T-cell lymphoma; REMS restricted. Not indicated for obesity. Native leptin is not a product. |
| Half-life | Roughly three to four hours after subcutaneous injection, which is why it is dosed daily. | 3.8 to 4.7 hours |
| Molecular weight | 16.2 kDa. A 147-amino-acid recombinant protein. | About 16.15 kDa (metreleptin, 147 residues, FDA label); native mature leptin is 146 residues, UniProt P41159, from an 18,641 Da 167-residue precursor |
| Mechanism | A recombinant analogue of human leptin, differing by an added methionine residue. Leptin is secreted by adipocytes in proportion to fat mass and acts at the leptin receptor on hypothalamic arcuate nucleus neurons, suppressing the orexigenic neuropeptide Y and agouti-related peptide neurons and stimulating the anorexigenic pro-opiomelanocortin neurons. It also signals nutritional sufficiency to the reproductive, thyroid and immune axes. In leptin deficiency all those signals read as starvation regardless of actual energy stores, which is why replacement does so much. In ordinary obesity leptin is already elevated and central resistance has developed, so adding more changes little. | Established in humans through deficiency and replacement: leptin binds the long form of the leptin receptor on hypothalamic neurons, signalling through JAK2 and STAT3, inhibiting the orexigenic NPY and AgRP neurons and activating POMC neurons upstream of the melanocortin-4 receptor. Absence of leptin in humans causes hyperphagia, severe early obesity, hypogonadotropic hypogonadism, altered thyroid function and impaired T cell immunity, all of which reverse with replacement. In lipodystrophy, replacement lowers glucose, triglycerides and liver fat and reduces food intake and resting metabolic rate. In common obesity, circulating leptin is already high and additional leptin produces small, dose-dependent effects, a state described as leptin resistance whose mechanism (transport across the blood-brain barrier, receptor signalling, SOCS3 feedback) is characterised mostly in rodents. Metreleptin is recombinant methionyl human leptin produced in E. coli: 147 amino acids, one disulfide bond between Cys-97 and Cys-147, about 16.15 kDa, differing from native mature leptin (146 residues) by an added N-terminal methionine. Renal clearance is the major route of elimination and clearance is expected to be delayed in the presence of leptin antibodies. |
| Human studies cited | 1 | 7 |
| Legal status, US | FDA-approved, prescription only | FDA-approved, prescription only |
Frequently asked questions
What is the difference between Metreleptin and Leptin?
Metreleptin: Transformative in people who make almost no leptin, and useless for ordinary obesity. The clearest case on this site of a hormone that only works as replacement. Leptin: The fat-derived hormone that tells the brain how much energy is stored. Replacing it transforms the rare people who lack it; in common obesity a 127-person randomised trial in 1999 found small dose-dependent weight loss and no drug came of it. Metreleptin is approved for generalised lipodystrophy with a boxed warning.
Which has stronger research evidence, Metreleptin or Leptin?
This database does not grade compounds. It counts what was run in people: 1 of the 1 studies cited on the Metreleptin profile were human work, against 7 of 10 for Leptin. Those counts are of our own citation lists and understate any larger literature, and neither is a recommendation.
Are Metreleptin and Leptin FDA-approved?
Metreleptin: FDA-approved as Myalept for complications of leptin deficiency in generalised lipodystrophy. Carries a boxed warning for anti-metreleptin antibodies with neutralising activity and for T-cell lymphoma risk, and is subject to a restricted distribution programme. Not approved for obesity or partial lipodystrophy.. Leptin: Metreleptin (Myalept) FDA-approved 24 February 2014 (BLA 125390, Chiesi) as an adjunct to diet for complications of leptin deficiency in congenital or acquired generalised lipodystrophy; Drugs@FDA marketing status Prescription on 11 September 2026. Boxed warning for neutralising anti-metreleptin antibodies and T-cell lymphoma; REMS restricted. Not indicated for obesity. Native leptin is not a product..
Reviewed Sep 2026. This page sets two published records side by side. It is educational, it is not medical advice, and it contains no dosing protocols or recommendations for personal use.