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

• Published in: Endocrine Vol. 64; no. 3; pp. 500 - 511
• Main Authors: Oral, Elif A., Gorden, Phillip, Cochran, Elaine, Araújo-Vilar, David, Savage, David B., Long, Alison, Fine, Gregory, Salinardi, Taylor, Brown, Rebecca J.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2019; Springer Nature B.V
• Subjects: Adolescent; Adult; Blood Glucose; Child; Diabetes; Diabetes mellitus; Endocrinology; Fasting; Female; Glucose; Glycated Hemoglobin A; Hemoglobin; Humanities and Social Sciences; Humans; Hypertriglyceridemia; Hypertriglyceridemia - blood; Hypertriglyceridemia - drug therapy; Hypoglycemia; Insulin; Insulin Resistance - physiology; Internal Medicine; Leptin; Leptin - adverse effects; Leptin - analogs & derivatives; Leptin - blood; Leptin - therapeutic use; Lipodystrophy; Lipodystrophy, Familial Partial - blood; Lipodystrophy, Familial Partial - drug therapy; Liver; Male; Medicine; Medicine & Public Health; Middle Aged; multidisciplinary; Nausea; Original Article; Pain; Prospective Studies; Science; Treatment Outcome; Triglycerides; Young Adult; Metreleptin; Lipodystrophy; Partial lipodystrophy; Diabetes mellitus; Leptin
• ISSN: 1355-008X; 1559-0100
• DOI: 10.1007/s12020-019-01862-8

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.