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

CONTEXT: Data quantifying the impact of metreleptin therapy on survival in non-human immunodeficiency virus (HIV)-related generalized lipodystrophy (GL) and partial lipodystrophy (PL) are unavailable. OBJECTIVE: This study aimed to estimate the treatment effect of metreleptin on survival in patients with GL and PL. DESIGN/SETTING/PATIENTS: Demographic and clinical characteristics were used to match metreleptin-treated and metreleptin-naïve patients with GL and PL. Differences in mortality risk were estimated between matched cohorts of metreleptin-treated and metreleptin-naïve patient cohorts using Cox proportional hazard models. Sensitivity analyses assessed the impact of study assumptions and the robustness of results. OUTCOME MEASURES: This study assessed time-to-mortality and risk of mortality. RESULTS: The analysis evaluated 103 metreleptin-naïve patients with characteristics matched to 103 metreleptin-treated patients at treatment initiation. Even after matching, some metabolic and organ abnormalities were more prevalent in the metreleptin-treated cohort due to bias toward treating more severely affected patients. A Cox proportional hazards model associated metreleptin therapy with an estimated 65% decrease in mortality risk (hazard ratio [HR] 0.348, 95% confidence interval (CI): 0.134–0.900; P = 0.029) even though the actual number of events were relatively small. Results were robust across a broad range of alternate methodological assumptions. Kaplan–Meier estimates of time-to-mortality for the metreleptin-treated and the matched metreleptin-naïve cohorts were comparable. CONCLUSIONS: 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. Confirmatory studies in additional real-world and clinical datasets are warranted.