Head to head
Mibavademab against Metreleptin
Both act on leptin signalling and both identified a population rather than a general use: mibavademab reduced weight only in people whose leptin was already below 8 ng per mL and did nothing in those with higher levels.
Column A
MibavademabMibavademab (REGN4461), leptin receptor agonist antibody
It reduced weight only in people whose leptin was already low, below 8 ng/mL, and did nothing in those with higher leptin. A rare case of a drug that identified who it is for.
Column B
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.
Side by side, on the facts we can check
| Attribute | Mibavademab | Metreleptin |
|---|---|---|
| Category | Metabolic | Hormone |
| FDA status | Investigational. Not approved. One phase 2 record carries status TERMINATED. | 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. |
| Half-life | Not asserted. Pharmacokinetics were characterised in a first-in-human study; no half-life figure was resolved in the sources loaded. Monoclonal antibodies of this class generally clear over weeks. | Roughly three to four hours after subcutaneous injection, which is why it is dosed daily. |
| Molecular weight | Fully human monoclonal antibody, roughly 150 kDa. Not a peptide. | 16.2 kDa. A 147-amino-acid recombinant protein. |
| Mechanism | A fully human monoclonal antibody that activates the human leptin receptor, LEPR, in the absence or presence of leptin. That distinguishes it from metreleptin, which is recombinant leptin and therefore useless where the receptor is unresponsive or where neutralising antibodies to leptin have developed. In leptin knockout mice it normalised body weight, food intake, blood glucose and insulin sensitivity, and in a generalised lipodystrophy model it relieved hyperphagia, hyperglycaemia, insulin resistance, dyslipidaemia and hepatic steatosis. | 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. |
| Human studies cited | 4 | 1 |
| Legal status, US | Investigational, not approved | FDA-approved, prescription only |
Frequently asked questions
What is the difference between Mibavademab and Metreleptin?
Mibavademab: It reduced weight only in people whose leptin was already low, below 8 ng/mL, and did nothing in those with higher leptin. A rare case of a drug that identified who it is for. 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.
Which has stronger research evidence, Mibavademab or Metreleptin?
This database does not grade compounds. It counts what was run in people: 4 of the 4 studies cited on the Mibavademab profile were human work, against 1 of 1 for Metreleptin. Those counts are of our own citation lists and understate any larger literature, and neither is a recommendation.
Are Mibavademab and Metreleptin FDA-approved?
Mibavademab: Investigational. Not approved. One phase 2 record carries status TERMINATED.. 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..
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.