OBJECTIVES : Metreleptin is the first approved medicine for the treatment of the complications of lipodystrophy. In the absence of head-to-head studies comparing metreleptin with best supportive care (BSC), the objective of this analysis was to estimate the treatment effect of metreleptin compared to BSC on the metabolic complications of lipodystrophy in generalised lipodystrophy (GL) or partial lipodystrophy (PL) patients.

METHODS : Patient-level data from two single arm studies were utilised to carry out an indirect treatment comparison: the GL/PL Natural History study, an observational study of patients receiving BSC, and the National Institute of Health (NIH) follow-up study, an extended follow-up to patients enrolled in the metreleptin NIH studies 991265/200110769. Analysis methodology was aligned to NICE Decision Support Unit guidelines. Two relevant adjustment methods were identified: multivariate regression and inverse probability weighting (IPW). Three covariates were included in the adjustment models – age, gender, and lipodystrophy type (generalised or partial). Outcomes evaluated included change in haemoglobin A1c (HbA1c), triglycerides, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) from baseline to 1 year, as well as the incidence of pancreatitis.

RESULTS : The results supported statistical rationale for using the IPW methodology as the primary analysis. A statistically significant adjusted treatment effect (ATE) was estimated for change in HbA1c (-1.52%; p<0.001), triglycerides (-915 mg/dl, p<0.001), ALT (-44 U/L, p<0.001), AST (-28 U/L, p<0.001) and episodes of pancreatitis (odds ratio (OR): 0.94, p=0.01) for metreleptin versus BSC. Results were consistent across multivariate regression analyses.

CONCLUSIONS : Metreleptin produced significant and clinical meaningful reductions in HbA1c, triglycerides, ALT, AST, and episodes of pancreatitis compared to BSC, and can be considered standard of care therapy to treat the metabolic complications in patients with lipodystrophy.