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 nonHIVrelated 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-naive patients with GL and PL. Differences in mortality risk were estimated between matched cohorts of metreleptin-treated and metreleptin-naive patient cohorts using Cox proportional hazard models. Sensitivity analyses assessed the impact of study assumptions and robustness of results. Outcome measures This study assessed time to mortality and risk of mortality. Results The analysis evaluated 103 metreleptin-naive 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 (HR 0.348, 95% 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-naive 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.