Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Metreleptin improves metabolic and hepatic endpoints in the treatment of non-HAART associated lipodystrophy syndromes: a meta-analysis into the effects of leptin replacement therapy. (#204)

Alexander J Rodriguez 1 , Teresa Neeman 2 , Aaron G Giles 1 , Claudio A Mastronardi 1 , Gilberto Paz-Filho 1
  1. Translational Medicine Group, Australian National University, Canberra, ACT, Australia
  2. Statistical Consulting Unit, Australian National University, Canberra, ACT, Australia

Introduction: Lipodystrophy syndromes (LS) are characterized by generalized/partial absence of subcutaneous adipose tissue, in which clinical manifestations consist of hypoleptinemia, hyperglycemia, elevated insulin resistance, dyslipidemia and hepatic steatosis. Leptin replacement therapy (LRT) is effective at improving glycemic control and liver injury, as well as restoring a normal lipid profile. Currently, no data exists that comprehensively and succinctly compiles the evidence from the literature, and demonstrates the effect of LRT on metabolic and hepatic parameters in LS patients.

Methods: A systematic review of the MEDLINE and Cochrane Library databases was conducted to identify studies assessing the effect of LRT on metabolic and hepatic endpoints. Standardized mean differences (SMD) and 95% confidence intervals of pooled results were calculated for overall changes in glucose homeostasis (fasting glycemia, insulin, HbA1c), plasma lipid profile (triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol), and hepatic morphology/function (liver volume/fat, albumin, ALT and AST), using an inverse-variance random-effects model.

Results: After screening, 14 studies were included for review, out of 270 studies eligible for inclusion. Meta-analysis of results from clinical studies in 243 patients showed that LRT decreased fasting glucose [0.76 SMD units (range 0.40-1.12), p<0.0001], HbA1c [0.55 (0.23-0.86), p=0.0006], triglycerides [1.12 (0.81-1.43), p<0.00001], total cholesterol [0.62 (0.21-1.02), p=0.003), liver volume [0.98 (0.52-1.43), p<0.0001], liver fat [0.67 (0.44-0.89), p<0.0001], ALT [0.44 (0.07-0.80), p=0.02] and AST [0.45 (0.17-0.73) p=0.002].

Conclusion: In patients with LS, LRT using metreleptin improves the outcome of several metabolic and hepatic parameters. Studies were limited by small populations and therefore large prospective trials are needed to validate these findings.