Metreleptin

Adipocytes store lipids to meet the fuel requirements of non-adipose tissues during fasting. In patients with generalized lipodystrophy, the deficiency of adipose tissue leads to hypertriglyceridemia and ectopic deposition of fat in non-adipose tissues such as liver and muscle, contributing to metabolic abnormalities including insulin resistance.

• MYALEPT is a leptin analog indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy. ( 1 ) Limitations of Use The safety and effectiveness of MYALEPT for the treatment of complications of partial lipodystrophy have not been established.

• General obesity not associated with congenital leptin deficiency. ( 4.1 ) Hypersensitivity to metreleptin.contraindicated

Administer as a subcutaneous injection once daily after the lyophilized cake is reconstituted with Bacteriostatic Water for Injection (BWFI) or preservative-free sterile Water for Injection (WFI). ( 2.1 ) The recommended daily dosages are: Body weight 40 kg or less: starting dose 0.06 mg/kg/day, increase or decrease by 0.02 mg/kg to a maximum daily dose of 0.13 mg/kg. ( 2.1 ) Males greater than 40 kg body weight: starting dose 2.5 mg/day, increase or decrease by 1.25 mg to 2.5 mg/day to a maximum dose of 10 mg/day. ( 2.1 ) Females greater than 40 kg body weight: starting dose 5 mg/day, increase or decrease by 1.25 mg to 2.5 mg/day to a maximum dose of 10 mg/day. ( 2.1 ) 2.1 Recommended Dosing See Table 1 for the recommended daily dose and maximum recommended daily dose in adults and pediatric patients. Based on clinical response (e.g., inadequate metabolic control) or other considerations (e.g., tolerability issues, excessive weight loss [especially in pediatric patients]), MYALEPT dosage may be decreased or increased to the maximum dosage listed in Table 1.

Anti-metreleptin antibodies with neutralizing activity: Could inhibit endogenous leptin action and/or result in loss of MYALEPT efficacy. Test for neutralizing antibodies in patients with severe infections or loss of efficacy during MYALEPT treatment. ( 5.1 ) T-cell lymphoma: Carefully consider benefits and risks of treatment with MYALEPT in patients with significant hematologic abnormalities and/or acquired generalized lipodystrophy. ( 5.2 ) Hypoglycemia: A dose adjustment, including possible large reductions, of insulin or insulin secretagogue may be necessary. Closely monitor blood glucose in patients on concomitant insulin or insulin secretagogue therapy. ( 5.4 ) Autoimmunity: Autoimmune disorder progression has been observed in patients treated with MYALEPT. Carefully consider benefits and risks of MYALEPT treatment in patients with autoimmune disease. ( 5.5 ) Hypersensitivity: Hypersensitivity reactions (e.g., anaphylaxis, urticaria or generalized rash) have been reported. Patient should promptly seek medical advice regarding suspected reactions. ( 5.6 ) Benzyl Alcohol Toxicity: Preservative-free sterile WFI recommended for neonates and infants.

Most common in clinical trials (≥10%): headache, hypoglycemia, decreased weight, abdominal pain. ( 5.4 , 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Chiesi Farmaceutici S.p.A. at 1-888-661-9260 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Open-Label, Single-Arm Study The safety of MYALEPT was evaluated in 48 patients with generalized lipodystrophy in a single-arm, open-label study [see Clinical Studies (14.1) ]. The median duration of exposure in this trial was 2.7 years with a range of 3.6 months to 10.9 years. The most frequent adverse reactions are summarized in Table 3. Table 3: Adverse Reactions of 5% or Greater Incidence in Patients with Generalized Lipodystrophy Receiving MYALEPT in an Open-Label, Single-Arm Study All Subjects N=48 (%) 1. Hypoglycemic events were assessed as mild, moderate, severe, or life threatening based on the protocol specified definitions: Mild: Documentation of low plasma glucose values with no symptoms; Moderate: Presence of clinical symptoms requiring ingestion of glucose, self-alleviated; Severe: Presence of neuroglycopenic symptoms requiring assistance from others for alleviation; Life threatening: Loss of consciousness and/or requiring intervention by administration of intravenous glucose or intramuscular glucagon.

8.1 Pregnancy Pregnancy Exposure Registry There is a program that monitors outcomes in women exposed to MYALEPT during pregnancy. Women who become pregnant during MYALEPT treatment are encouraged to enroll. Patients or their physicians should call 1-855-669-2537 to enroll. Risk Summary Available pharmacovigilance reports with the use of MYALEPT in pregnant women are insufficient to evaluate for any drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. These reports describe similar adverse pregnancy outcomes as those documented in women with lipodystrophy (see Clinical Considerations ) . In an animal reproduction study, no adverse developmental effects were observed with subcutaneous administration of metreleptin to pregnant mice during organogenesis at doses 7- and 15-fold the maximum recommended clinical dose, based on body surface area of a 20- and 60-kg patient, respectively. In a pre- and postnatal development study in mice, subcutaneous administration of metreleptin caused prolonged gestation and dystocia resulting in maternal death during parturition and lower survival of offspring in the immediate postnatal period at doses starting approximately at the maximum recommended clinical dose (see Data ) . MYALEPT contains benzyl alcohol when reconstituted with BWFI. MYALEPT contains no preservative when reconstituted with WFI.

Metabolism

There are limited data on the pharmacokinetics of metreleptin in patients with generalized lipodystrophy, and therefore, no formal exposure-response analysis has been performed. It should be noted that the leptin assay measures both endogenous leptin as well as exogenously administered metreleptin.

In one post-marketing case, a dose miscalculation resulted in an infant being exposed to a 10-fold overdose of metreleptin for 8 months. In this case, prolonged overdose was associated with severe anorexia causing vitamin and zinc deficiencies, iron deficiency anemia, protein calorie malnutrition, and poor weight gain, which resolved following supportive treatment and dose adjustment. In the event of an overdose, patients should be monitored and appropriate supportive treatment be initiated as dictated by the patient's clinical status.

• Feb 24, 2014BLABLA125390Chiesi Farmaceutici Spa

1. 1Product Dose Omission Issue987.9%
2. 2Therapy Cessation927.5%
3. 3Weight Decreased927.5%
4. 4Blood Glucose Increased826.7%
5. 5Drug Ineffective776.2%
6. 6Therapy Interrupted665.4%
7. 7Off Label Use655.3%
8. 8Nausea594.8%
9. 9Blood Triglycerides Increased534.3%
10. 10Treatment Noncompliance524.2%
11. 11Weight Increased514.1%
12. 12Injection Site Pain483.9%
13. 13Maternal Exposure During Pregnancy473.8%
14. 14Decreased Appetite463.7%
15. 15Glycosylated Haemoglobin Increased413.3%

The 10 most recently updated of 40 ClinicalTrials.gov registrations naming Metreleptin as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Natural History of Pregnancy and Pregnancy Outcomes in Metreleptin-Treated vs Untreated Subjects With Lipodystrophy
  Recruiting · Observational · 90 enrolled · National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  NCT05419037updated 2026-05-12
• Compassionate Use of Metreleptin in Previously Treated People With Generalized Lipodystrophy
  Active not recruiting · Phase 3 · Interventional · 24 enrolled · National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  NCT02262832updated 2026-05-12
• Compassionate Use of Metreleptin in Previously Treated People With Partial Lipodystrophy
  Active not recruiting · Phase 2 · Interventional · 29 enrolled · National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  NCT02262806updated 2026-05-12
• A Study of the Safety of Mibavademab in Pediatric and Adult Participants Switching From Metreleptin to Mibavademab for the Treatment of Generalized Lipodystrophy (GLD)
  Active not recruiting · Phase 3 · Interventional · 9 enrolled · Regeneron Pharmaceuticals
  NCT06548100updated 2026-04-07
• Open-label Extension Study to Evaluate Metreleptin in Patients With Partial Lipodystrophy
  Recruiting · Phase 3 · Interventional · 24 enrolled · Amryt Pharma
  NCT06679270updated 2026-02-02
• Expanded Access Metreleptin Study
  Available · Expanded access · University of Michigan
  NCT02404896updated 2026-02-02
• MEASuRE: Metreleptin Effectiveness And Safety Registry
  Recruiting · Observational · 100 enrolled · Amryt Pharma
  NCT02325674updated 2026-01-20
• Open-label Study to Evaluate Metreleptin in Children Under 6 Years of Age With Generalised Lipodystrophy
  Recruiting · Phase 3 · Interventional · 15 enrolled · Amryt Pharma
  NCT06502990updated 2026-01-20
• Metreleptin in Anorexia Nervosa
  Recruiting · Phase 2 · Interventional · 50 enrolled · Gabriella Milos
  NCT06305182updated 2026-01-15
• Immunogenicity of Metreleptin in Patients With Generalized Lipodystrophy
  Completed · Phase 4 · Interventional · 11 enrolled · Aegerion Pharmaceuticals, Inc.
  NCT04026178updated 2025-11-26

Frequently asked questions

How does Metreleptin work?

Adipocytes store lipids to meet the fuel requirements of non-adipose tissues during fasting. In patients with generalized lipodystrophy, the deficiency of adipose tissue leads to hypertriglyceridemia and ectopic deposition of fat in non-adipose tissues such as liver and muscle, contributing to metabolic abnormalities including insulin resistance.

What is Metreleptin used for?

According to FDA labeling, Metreleptin carries indications including: MYALEPT is a leptin analog indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy. ( 1 ) Limitations of Use The safety and effectiveness of MYALEPT for the treatment of complications of partial lipodystrophy have not been established.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Metreleptin?

Metreleptin is classified as Amino acids and derivatives, Leptin Analog, Cytokine Receptor Superfamily Interactions.

What are the brand names for Metreleptin?

Metreleptin is marketed under brand names including Myalept.

What are the contraindications for Metreleptin?

Metreleptin labeling lists contraindications including: General obesity not associated with congenital leptin deficiency. ( 4.1 ) Hypersensitivity to metreleptin.. Always consult the full prescribing information and a clinician.