Effect of Leptin Therapy on Survival in Generalized and Partial Lipodystrophy: A Matched Cohort Analysis

J Clin Endocrinol Metab 2021 Jul 13;106(8):e2953-e2967. doi: 10.1210/clinem/dgab216.

PMID: 33822100

Keziah Cook, Omer Ali, Baris Akinci

Highlights: Metreleptin therapy was associated with a reduction in mortality risk in patients with lipodystrophy syndromes despite greater disease severity in treated patients, supporting the view that metreleptin can have a positive disease-modifying impact.

Abstract

Context: In the context of non-HIV-related generalized lipodystrophy (GL) and partial lipodystrophy (PL), there are no data on the influence of metreleptin treatment on survival.

Objective: The goal of this study was to determine the effect of metreleptin therapy on survival in patients with GL and PL.

Design/setting/patients: Metreleptin-treated and metreleptin-naive patients with GL and PL were matched based on demographic and clinical characteristics. Cox proportional hazard models were used to evaluate differences in mortality risk between matched cohorts of metreleptin-treated and metreleptin-naive patient populations. The influence of study assumptions and the robustness of results were examined using sensitivity analyses.

Outcome measures: Time-to-mortality and mortality risk were both measured in this study.

Results: The study looked at 103 metreleptin-naive individuals who had similar characteristics to 103 metreleptin-treated patients at the start of treatment. Due to a bias toward treating more seriously affected patients, several metabolic and organ abnormalities were more common in the metreleptin-treated cohort even after matching. Despite the limited number of events, a Cox proportional hazards model linked metreleptin treatment with a 65% reduction in mortality risk (hazard ratio [HR] 0.348, 95% confidence interval (CI): 0.134-0.900; P = 0.029). Results were robust across a broad range of alternate methodological assumptions. The metreleptin-treated and matched metreleptin-naive groups had similar Kaplan-Meier estimates of time-to-mortality.

Conclusions: Despite increased disease severity in treated individuals, metreleptin therapy was linked with a decrease in mortality risk in patients with lipodystrophy syndromes, supporting the notion that metreleptin can have a beneficial disease-modifying effect. Confirmatory research in more real-world and clinical datasets is required.

Keywords: CGL, FPLD, hepatic steatosis, leptin, lipodystrophy, metreleptin