Long-term effectiveness and safety of metreleptin in the treatment of patients with partial lipodystrophy

Endocrine. 2019 Jun;64(3):500-511. doi: 10.1007/s12020-019-01862-8. Epub 2019 Feb 25.


Purpose: To evaluate the effects of metreleptin in patients with partial lipodystrophy (PL).

Methods: Patients aged ≥ 6 months with PL, circulating leptin < 12.0 ng/mL, and diabetes mellitus, insulin resistance, or hypertriglyceridemia received metreleptin doses (once or twice daily) titrated to a mean of 0.124 mg/kg/day. Changes from baseline to month 12 in glycated hemoglobin (HbA1c) and fasting serum triglycerides (TGs; co-primary endpoints), fasting plasma glucose (FPG), and liver volume were evaluated. Additional assessments included the proportions of patients achieving target decreases in HbA1c or fasting TGs at month 12, long-term treatment effects, and treatment-emergent adverse events (TEAEs).

Results: Significant (p < 0.05) reductions in HbA1c (-0.6%), fasting TGs (-20.8%), FPG (-1.2 mmol/L), and liver volume (-13.4%) were observed in the overall PL population at month 12. In a subgroup of patients with baseline HbA1c ≥ 6.5% or TGs ≥ 5.65 mmol/L, significant (p < 0.05) reductions were seen in HbA1c (-0.9%), fasting TGs (-37.4%), FPG (-1.9 mmol/L), and liver volume (-12.4%). In this subgroup, 67.9% of patients had a ≥ 1% decrease in HbA1c or ≥ 30% decrease in fasting TGs, and 42.9% had a ≥ 2% decrease in HbA1c or ≥ 40% decrease in fasting TGs. Long-term treatment in this subgroup led to significant (p < 0.05) reductions at months 12, 24, and 36 in HbA1c, fasting TGs, and FPG. Metreleptin was well tolerated with no unexpected safety signals. The most common TEAEs were abdominal pain, hypoglycemia, and nausea.

Conclusions: In patients with PL, treatment with metreleptin was well tolerated and resulted in improvements in glycemic control, hypertriglyceridemia, and liver volume.

Keywords: Diabetes mellitus; Leptin; Lipodystrophy; Metreleptin; Partial lipodystrophy.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Blood Glucose
  • Child
  • Female
  • Glycated Hemoglobin
  • Humans
  • Hypertriglyceridemia / blood
  • Hypertriglyceridemia / drug therapy*
  • Insulin Resistance / physiology
  • Leptin / adverse effects
  • Leptin / analogs & derivatives*
  • Leptin / blood
  • Leptin / therapeutic use
  • Lipodystrophy, Familial Partial / blood
  • Lipodystrophy, Familial Partial / drug therapy*
  • Male
  • Middle Aged
  • Prospective Studies
  • Treatment Outcome
  • Young Adult


  • Blood Glucose
  • Glycated Hemoglobin A
  • Leptin
  • metreleptin