What is the treatment for patients with confirmed leptin deficiency using Metreleptin (metreleptin)?

Metreleptin Treatment for Confirmed Leptin Deficiency

Metreleptin is FDA-approved as adjunct to diet for replacement therapy to treat complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy. 1

Indication and Patient Selection

Metreleptin is specifically indicated for generalized lipodystrophy with confirmed leptin deficiency and metabolic complications—it is NOT approved for partial lipodystrophy, HIV-related lipodystrophy, obesity, or metabolic disease without concurrent generalized lipodystrophy. 1

Required Criteria for Treatment:

• Confirmed congenital or acquired generalized lipodystrophy 1
• Low circulating leptin levels 2
• At least one metabolic abnormality: diabetes mellitus, insulin resistance, or hypertriglyceridemia 2

Dosing Algorithm

For Patients ≤40 kg (Pediatric and Small Adults):

• Starting dose: 0.06 mg/kg/day subcutaneously 1
• Dose adjustments: Increase or decrease by 0.02 mg/kg increments 1
• Maximum dose: 0.13 mg/kg/day 1

For Males >40 kg:

• Starting dose: 2.5 mg/day subcutaneously 1
• Dose adjustments: 1.25-2.5 mg increments 1
• Maximum dose: 10 mg/day 1

For Females >40 kg:

• Starting dose: 5 mg/day subcutaneously 1
• Dose adjustments: 1.25-2.5 mg increments 1
• Maximum dose: 10 mg/day 1

Administer once daily at the same time each day, regardless of meal timing. 1

Expected Clinical Outcomes

Metabolic Improvements (Based on Long-term Data):

At 12 months of treatment, expect substantial reductions in HbA1c (-2.2%), fasting glucose (-3.0 mmol/L), and triglycerides (-32% mean reduction). 2

• 80% of patients achieve either ≥1% decrease in HbA1c OR ≥30% decrease in triglycerides by month 12 2
• 66% achieve ≥2% decrease in HbA1c OR ≥40% decrease in triglycerides by month 12 2
• Liver volume decreases by mean 33.8% at 12 months 2
• These improvements are sustained through 36 months of treatment 2, 3

Medication Reduction:

• 41% of patients discontinue insulin 2
• 22% discontinue oral antidiabetic medications 2
• 24% discontinue lipid-lowering medications 2

Clinical Response Timeline:

Metabolic benefits are evident within weeks of starting therapy and are durable over years. 4

Critical Safety Warnings and Monitoring

BOXED WARNING - Anti-Metreleptin Antibodies:

Anti-metreleptin antibodies with neutralizing activity can develop, potentially inhibiting endogenous leptin action and causing loss of efficacy. 1

• Monitor for severe infections or signs of loss of metabolic control 1
• Test for neutralizing antibodies if severe infections develop or efficacy is lost 1
• Contact manufacturer at 1-866-216-1526 for neutralizing antibody testing 1

BOXED WARNING - Lymphoma Risk:

T-cell lymphoma has been reported in patients with acquired generalized lipodystrophy, both treated and untreated with metreleptin. 1

• Carefully assess benefits versus risks in patients with significant hematologic abnormalities 1
• Particularly cautious consideration required for acquired generalized lipodystrophy patients 1

Hypoglycemia Management:

Large reductions in insulin or insulin secretagogue doses may be necessary—closely monitor blood glucose in patients on concomitant therapy. 1

Autoimmunity:

Autoimmune disorder progression has been observed; carefully weigh benefits versus risks in patients with existing autoimmune disease. 1

Additional Monitoring:

• Hypersensitivity reactions including anaphylaxis have been reported 1
• Use preservative-free sterile water for injection in neonates and infants to avoid benzyl alcohol toxicity 1

REMS Program Requirement

Metreleptin is available ONLY through a restricted REMS program due to the risks of neutralizing antibodies and lymphoma. 1

Common Adverse Events

The most common adverse reactions (≥10%) include headache, hypoglycemia, decreased weight, and abdominal pain. 1 Most treatment-emergent adverse events are mild to moderate in severity. 2

Important Clinical Context

In congenital leptin deficiency, leptin administration rescues quantitative and qualitative defects in circulating CD4 T cells and reverses immune dysfunction. 5 This immune restoration is a critical component of the therapeutic benefit beyond metabolic improvements alone. 5