Metreleptin
Replacement leptin for people born without, or who lose, nearly all their body fat
Metreleptin is human leptin made in bacteria, with one extra amino acid at the front. People with generalized lipodystrophy have almost no fat tissue, so they make almost no leptin, and they develop severe diabetes, very high triglycerides and fatty liver. A daily injection of metreleptin replaces the missing hormone. It is a restricted drug in the US, with a boxed warning about neutralising antibodies and lymphoma.
Manufacturer's recommended dosing (FDA label): 0.06 mg/kg (up to 0.13 mg/kg), Once daily, Subcutaneous Details ↓
Recommended Dosing
Manufacturer's recommended dosing (FDA label)
From the prescribing information. Other doses studied, if any, are in the full dosing data below.
Work out syringe units → · New to syringes? · All dosing data ↓
What is it?
Leptin is the hormone fat cells release to tell the brain how much energy the body has stored. When fat tissue is missing, as in the rare genetic and acquired forms of generalized lipodystrophy, leptin levels fall to almost nothing. Without that signal, fat collects in the liver, insulin stops working well and triglycerides climb, so most patients have diabetes and fatty liver. Metreleptin, recombinant methionyl human leptin, was developed to put the hormone back.
The first proof came from the US National Institutes of Health. In 2002, nine women with lipodystrophy and very low leptin who were given recombinant leptin for four months saw triglycerides fall by about 60%, liver volume shrink by 28% and HbA1c drop by almost two points. The NIH study kept enrolling patients from 2000 onward, and FDA approved Myalept in February 2014 for congenital or acquired generalized lipodystrophy.
Those long-term results are large for a metabolic drug. In 66 people with generalized lipodystrophy, HbA1c fell 2.2 points and triglycerides by about a third after a year, liver volume shrank by a third, and many patients stopped insulin or lipid drugs. Children responded in the same way, and liver biopsies improved over several years. Real-world series from France, Japan and the Middle East have reported similar changes, and a matched NIH cohort analysis linked treatment with lower mortality.
Partial lipodystrophy is less clear-cut. People with partial forms keep some fat and some leptin, and their average responses are smaller; patients with the worst triglycerides and the lowest leptin gain the most. The US label says safety and effectiveness in partial lipodystrophy have not been established, and it is not approved for liver disease alone, for HIV-related lipodystrophy or for ordinary obesity.
Obesity is the obvious question, and the answer so far is no. People with common obesity already have high leptin, and the label lists general obesity as a contraindication. In trials in people with obesity, almost everyone formed antibodies against metreleptin, and a few developed antibodies that neutralised it as their weight rose. Pairing it with the amylin analogue pramlintide produced more weight loss than either drug alone in one 24-week trial, but that combination was never approved.
The safety profile explains why it is tightly controlled. The boxed warning covers antibodies that can neutralise both the drug and any leptin the body still makes, sometimes with severe infection or worse metabolic control, and T-cell lymphoma, which has been seen in acquired generalized lipodystrophy with and without treatment. In the US it is available only through the Myalept REMS programme. It is a lifelong hormone replacement for a rare disease, not a weight-loss peptide.
Mechanism of Action
Metreleptin binds and activates the leptin receptor, standing in for the leptin that missing fat tissue cannot make. The label describes it as a leptin analog that replaces the hormone.
Appetite and energy signalling
Restoring a leptin signal reduced food intake and resting metabolic rate in the first NIH patients (PMID 11856796, References).
Insulin sensitivity and lipids
With less fat stored in liver and muscle, HbA1c and triglycerides fall and many patients reduce insulin (PMID 29644599).
Immune response to the drug
Most patients form antibodies; a few neutralise metreleptin and any remaining native leptin (PMID 26589105; label boxed warning).
Published Research
The studies behind metreleptin, read from their PubMed abstracts. Most are open-label: lipodystrophy is too rare, and its untreated course too harsh, for long placebo-controlled trials.
Generalized lipodystrophy: long-term results
In 66 patients given a mean 0.10 mg/kg a day, HbA1c fell by 2.2 points, fasting glucose by 3.0 mmol/L and triglycerides by about 32% after 12 months, liver volume shrank by about a third, and 41% of insulin users stopped insulin; side effects were mostly mild or moderate.
Partial lipodystrophy: smaller, selective gains
In partial lipodystrophy, a mean 0.124 mg/kg a day lowered HbA1c by 0.6 points and triglycerides by about 21% at 12 months; in the subgroup with HbA1c of 6.5% or more or very high triglycerides the falls were larger and lasted to 36 months.
Generalized against partial, side by side
Comparing 55 generalized and 31 partial lipodystrophy patients at the NIH, a year of metreleptin lowered HbA1c and triglycerides in both, with bigger changes in the generalized group; partial patients with milder disease or leptin above 4 ng/mL gained little.
Children and teenagers
In 53 patients aged 6 months to 18 years, HbA1c fell from 8.3% to 6.5% and median triglycerides from 374 to 189 mg/dL in a year, liver enzymes roughly halved, liver biopsies improved over about three years, and growth and puberty were not affected.
Antibodies are almost universal
Anti-metreleptin antibodies developed in 96–100% of 579 people with obesity and 86–92% of 134 with lipodystrophy; neutralising activity appeared in three obese patients alongside weight gain and in four with generalized lipodystrophy alongside worse metabolic control, two of whom had sepsis.
Ten years of use in France
In 47 French patients, HbA1c fell from 8.4% to 6.8% and triglycerides by about 40% after a year in generalized lipodystrophy, while average HbA1c did not change in partial lipodystrophy, though about 60% of partial patients were classed as responders.
Protein in the urine
Patients with generalized lipodystrophy started with more albumin and protein in their urine than those with partial forms; up to 24 months of metreleptin reduced both in the generalized group but not in the partial group, and kidney filtration did not change.
Japan's post-marketing surveillance
Following all 48 Japanese patients treated from launch in 2013 to 2021, 15 had adverse drug reactions, most often reduced appetite and neutralising antibodies, without an overall safety concern; HbA1c and triglycerides fell within months and stayed lower for up to 7 years.
Congenital disease in the Middle East
In 38 patients with congenital generalized lipodystrophy, mostly children, HbA1c fell a median 1.4 points and triglycerides by 1.5 mmol/L at about six months, with liver enzymes also lower; most changes held at two years, with no new safety signals.
A rare insulin-receptor disease
In Rabson-Mendenhall syndrome, caused by faulty insulin receptors, patients on at least 0.15 mg/kg a day kept HbA1c about 1.8 points lower than untreated patients over 90 months, which the authors tied to lower appetite and body mass rather than better growth.
Type 1 diabetes pilot
In eight adults with poorly controlled type 1 diabetes given metreleptin twice daily for 20 weeks, HbA1c did not fall significantly, though weight dropped by 4.7 kg and insulin dose by 15%.
Obesity, with and without pramlintide
In a 20-week trial in overweight and obese adults after a pramlintide lead-in, metreleptin 5 mg twice daily alone gave 8.2% weight loss, pramlintide alone 8.4% and the two together 12.7%; injection-site events and nausea were the commonest side effects. The combination arm involved a second drug.
Where it fits and why it stalled
This review covers leptin physiology, the evidence for metreleptin in generalized lipodystrophy and its possible uses in partial lipodystrophy, fatty liver and obesity, and names immunogenicity and safety as the main barriers to wider approval.
Dosing Data
These are the Myalept label's daily doses, set by weight and sex and adjusted to metabolic response. It is prescribed only through the Myalept REMS programme for generalized lipodystrophy.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Metreleptin is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
The approved product Myalept (metreleptin injection) is a powder that is mixed before use, with the liquid and volume its label names. Follow the label, not a general example. Its label says: “MYALEPT can be reconstituted aseptically with 2.2 mL of sterile Bacteriostatic Water for Injection (BWFI), USP (0.9% benzyl alcohol), or with 2.2 mL of sterile Water for Injection (WFI).”
Source: Myalept (metreleptin injection) label, sections 2 and 3 (DailyMed version 18, effective March 25, 2024).
Storage before and after mixing
Before mixing or first use: the label sentences we read do not say.
After mixing or first use: “When reconstituted in BWFI, MYALEPT solution can be used within 3 days when stored in the refrigerator between 36°F and 46°F (2°C and 8°C) and protected from light.” “Discard unused reconstituted solution after 3 days.” “Unused reconstituted solution cannot be saved for later use and should be discarded.”
Source: Myalept (metreleptin injection) label, sections 16 and 2 (DailyMed version 18, effective March 25, 2024).
How it is taken
As the approved label gives it: Subcutaneous (Once daily; Label: body weight 40 kg or less).
Source: Manufacturer's recommended dosing (FDA label): the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: a half-life of 3.8 to 4.7 hours. After about five half-lives almost none is left.
How long the doses were given: Label: body weight 40 kg or less: Long term; change by 0.02 mg/kg steps; Label: males over 40 kg: Long term; change by 1.25–2.5 mg steps; Label: females over 40 kg: Long term; change by 1.25–2.5 mg steps.
When effects appear: unknown; no source on this page gives a time to effect for Metreleptin. Results reported in the studies are under Published Research.
Source: half-life: Myalept (metreleptin) for injection US prescribing information (Chiesi; DailyMed set d3b50bbd, version 18, effective March 25, 2024; read October 28, 2026), section 12.3; Manufacturer's recommended dosing (FDA label), the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Anti-drug antibodies in most patients; neutralising antibodies in a few, with worse control or infection; Abdominal pain, nausea and hypoglycaemia (partial lipodystrophy study); Reduced appetite and weight loss, sometimes excessive in children; Injection-site reactions. Full list and cautions ↓
Boxed warning on the label: Risk of anti-metreleptin antibodies with neutralizing activity and risk of lymphoma.
When the label says to stop or get help:
- Hypersensitivity: Hypersensitivity reactions (e.g., anaphylaxis, urticaria or generalized rash) have been reported. Patient should promptly seek medical advice regarding suspected reactions.
Source: Myalept (metreleptin injection) label, boxed warning and section 5 (DailyMed version 18, effective March 25, 2024); the Side Effects section below (“From the studies above”).
Interactions
- drugs metabolised by CYP450 with a narrow therapeutic index (for example warfarin, cyclosporine, theophylline) and oral contraceptives: no formal interaction studies; leptin is a cytokine that may alter CYP450 formation, so the label advises monitoring effect or drug levels and adjusting those drugs when metreleptin is started or stopped
Every peptide's record, with its source: the interaction matrix.
Source: MYALEPT (metreleptin), US prescribing information, section 7. DailyMed version 18, effective March 25, 2024, read October 28, 2026.
Checking what you bought
Unknown: no published independent test of Metreleptin products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: FDA Approved (FDA-approved February 24, 2014 as Myalept (BLA 125390). Sport: Not on the 2026 List.
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the studies above.
Contraindications & Cautions
Boxed warning, contraindications and warnings from the Myalept label (DailyMed set d3b50bbd, version 18, effective March 25, 2024).
Legal Status
Metreleptin is an FDA-approved prescription biologic with a restricted distribution programme.
Frequently Asked Questions
?Can metreleptin be used for weight loss?
No. The label lists general obesity as a contraindication, people with obesity already have high leptin, and obesity trials found antibodies in nearly every patient, with neutralising antibodies in a few.
?Who is it for?
People with congenital or acquired generalized lipodystrophy, who have very little fat tissue and very low leptin, and the metabolic damage that follows.
?Does it help partial lipodystrophy?
Some patients improve, mostly those with very high triglycerides and low leptin, but the US label says benefit in partial lipodystrophy has not been established.
?What is the REMS?
A restricted programme in which prescribers and pharmacies must be certified, required because of the neutralising-antibody and lymphoma risks in the boxed warning.
?Is it the same as natural leptin?
Almost: it has the same 146-amino-acid chain plus one extra methionine at the start, and it is not glycosylated (label).
References
- [clinical-trial] Brown RJ, et al. "Long-term effectiveness and safety of metreleptin in the treatment of patients with generalized lipodystrophy." Endocrine, 2018;60(3):479-489. PMID: 29644599.
- [clinical-trial] Oral EA, et al. "Long-term effectiveness and safety of metreleptin in the treatment of patients with partial lipodystrophy." Endocrine, 2019;64(3):500-511. PMID: 30805888.
- [clinical-trial] Diker-Cohen T, et al. "Partial and generalized lipodystrophy: comparison of baseline characteristics and response to metreleptin." J Clin Endocrinol Metab, 2015;100(5):1802-10. PMID: 25734254.
- [clinical-trial] Brown RJ, et al. "Effects of Metreleptin in Pediatric Patients With Lipodystrophy." J Clin Endocrinol Metab, 2017;102(5):1511-1519. PMID: 28324110.
- [clinical-trial] Chan JL, et al. "Immunogenicity associated with metreleptin treatment in patients with obesity or lipodystrophy." Clin Endocrinol (Oxf), 2016;85(1):137-49. PMID: 26589105.
- [pubmed] Mosbah H, et al. "Therapeutic indications and metabolic effects of metreleptin in patients with lipodystrophy syndromes: Real-life experience from a national reference network." Diabetes Obes Metab, 2022;24(8):1565-1577. PMID: 35445532.
- [pubmed] Lee HL, et al. "Effects of Metreleptin on Proteinuria in Patients With Lipodystrophy." J Clin Endocrinol Metab, 2019;104(9):4169-4177. PMID: 30990519.
- [pubmed] Ebihara K, et al. "Postmarketing Surveillance of the Safety and Effectiveness of Metreleptin in Patients with Lipodystrophy in Japan." J Endocr Soc, 2026;10(2):bvaf216. PMID: 41608200.
- [pubmed] Alfadhel M, et al. "Effect of metreleptin treatment in congenital generalized lipodystrophy: a retrospective analysis from the MENA region." J Endocrinol Invest, 2026;49(10):2951-2962. PMID: 42507316.
- [clinical-trial] Okawa MC, et al. "Long-Term Effects of Metreleptin in Rabson-Mendenhall Syndrome on Glycemia, Growth, and Kidney Function." J Clin Endocrinol Metab, 2022;107(3):e1032-e1046. PMID: 34718628.
- [clinical-trial] Vasandani C, et al. "Efficacy and Safety of Metreleptin Therapy in Patients With Type 1 Diabetes: A Pilot Study." Diabetes Care, 2017;40(5):694-697. PMID: 28223297.
- [clinical-trial] Ravussin E, et al. "Enhanced weight loss with pramlintide/metreleptin: an integrated neurohormonal approach to obesity pharmacotherapy." Obesity (Silver Spring), 2009;17(9):1736-43. PMID: 19521351.
- [review] Tchang BG, et al. "Metreleptin and generalized lipodystrophy and evolving therapeutic perspectives." Expert Opin Biol Ther, 2015;15(7):1061-75. PMID: 26063386.
- [clinical-trial] Oral EA, et al. "Leptin-replacement therapy for lipodystrophy." N Engl J Med, 2002;346(8):570-8. PMID: 11856796.
- [pubmed] Cook K, et al. "Effect of Leptin Therapy on Survival in Generalized and Partial Lipodystrophy: A Matched Cohort Analysis." J Clin Endocrinol Metab, 2021;106(8):e2953-e2967. PMID: 33822100.
- [clinical-trial] Chou SH, et al. "Leptin is an effective treatment for hypothalamic amenorrhea." Proc Natl Acad Sci U S A, 2011;108(16):6585-90. PMID: 21464293.
- [clinical-trial] Sienkiewicz E, et al. "Long-term metreleptin treatment increases bone mineral density and content at the lumbar spine of lean hypoleptinemic women." Metabolism, 2011;60(9):1211-21. PMID: 21741057.
- [fda] Drugs@FDA (openFDA): BLA125390, MYALEPT (metreleptin), Chiesi Farmaceutici; original approval February 24, 2014; marketing status Prescription. Read October 28, 2026.
- [fda-pi] Myalept (metreleptin) for injection, US prescribing information, Chiesi USA. DailyMed set d3b50bbd, version 18, effective March 25, 2024; read October 28, 2026.
Sources & Citations
Studies were read from their PubMed abstracts; doses, half-life and warnings from the Myalept label on DailyMed (set d3b50bbd, version 18, effective March 25, 2024), read October 28, 2026; approval from Drugs@FDA.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.