ESPE Abstracts

Generalized lipodystrophy (GLD) is characterized by near total loss of subcutaneous fat, leading to low concentrations of leptin. Complications of GLD are heterogenous, including severe insulin resistance, diabetes, hypertriglyceridemia, pancreatitis, liver, kidney, and heart disease, and reproductive dysfunction. Leptin replacement therapy using metreleptin improves many of these metabolic abnormalities. A lipodystrophy severity score (LDS) has been developed to quantify disease severity in patients with diverse manifestations of lipodystrophy. This score has not yet been assessed using real-world patient data. We hypothesized that LDS would improve after metreleptin treatment in patients with GLD. We conducted a single-center retrospective analysis of subjects with congenital and acquired generalized lipodystrophy who were treated with metreleptin for 6-12 months. LDS total score (maximum 336 [female] or 328 [male]) and subscores for domains of diabetes/insulin resistance, microvascular complications of diabetes, lipids, cardiovascular, liver, kidney, reproductive, and “other” (e.g. immunodeficiency) were calculated based on laboratory, imaging, and medical history data. 63 subjects were included: 79% female, 76% congenital, 24% acquired, age 16±12 years. At baseline, LDS median(interquartile range) was 46(29-59) (range 6 to 98), which decreased to 32(25-43) and 26(18-37) after 6 and 12 months of metreleptin (P <0.0001), respectively. The percent reduction in LDS relative to baseline was 25(12-44) and 29(6-53) after 6 and 12 months. 48% and 54% of patients had at least 25% improvement in LDS after 6 and 12 months. After 6 and 12 months of metreleptin, diabetes subscore decreased from 13(3-15) to 6(0-11) and 3(0-9) (P <0.0001), lipid subscore decreased from 6(4-12) to 4(2-7) and 4(1-7) (P <0.0001), liver subscore decreased from 19(12-23) to 15(10-21) and 12(7-19) (P <0.0001), kidney subscore decreased from 6(4-8) to 3(1-4) and 3(1-4) (P = 0.0002), and reproductive subscore decreased from 0(0-3) to 0(0-0) and 0(0-0) (P = 0.0002). Microvascular, cardiovascular, and “other” subscores were 0(0-0), 0(0-3), and 0(0-0) at baseline and did not change after metreleptin. In conclusion, patients with GLD treated with metreleptin demonstrated significant improvement in overall LDS, with 54% having at least 25% reduction at month 12, representing a clinically important difference. Improved diabetes subscore was the largest contributor to improved LDS, although improvements were observed in most organ systems. This study demonstrates the utility of LDS to measure global improvements in patients with lipodystrophy across multiple organ systems.