Comparison of efficacy and safety of leptin replacement therapy in moderately and severely hypoleptinemic patients with familial partial lipodystrophy of the Dunnigan variety.

Context: Leptin replacement therapy improves metabolic complications in patients with lipodystrophy and severe hypoleptinemia (SH), but whether the response is related to the degree of hypoleptinemia remains unclear. Objective: The aim of the study was to compare efficacy of leptin therapy in familial partial lipodystrophy, Dunnigan variety (FPLD) patients with SH (serum leptin <7th percentile of normal) vs. those with moderate hypoleptinemia (MH; serum leptin in 7th to 20th percentiles). Design, Setting, and Patients: We conducted an open-label, parallel group, observational study in 14 SH (mean ± sd, serum leptin, 1.9 ± 1.1 ng/ml) and 10 MH (serum leptin, 5.3 ± 1.0 ng/ml) women with FPLD. Intervention: Patients received 0.08 mg/kg · d of metreleptin by twice daily sc injections for 6 months. Main Outcome Measures: The primary outcome variable was change in fasting serum triglycerides. Other secondary variables were fasting plasma glucose and insulin, insulin sensitivity, hemoglobin A1c, and hepatic trig...