, Volume 60, Issue 3, pp 479–489 | Cite as

Long-term effectiveness and safety of metreleptin in the treatment of patients with generalized lipodystrophy

  • Rebecca J. Brown
  • Elif A. Oral
  • Elaine Cochran
  • David Araújo-Vilar
  • David B. Savage
  • Alison Long
  • Gregory Fine
  • Taylor Salinardi
  • Phillip Gorden
Original Article



The purpose of this study is to summarize the effectiveness and safety of metreleptin in patients with congenital or acquired generalized lipodystrophy.


Patients (n = 66) aged ≥6 months had lipodystrophy, low circulating leptin, and ≥1 metabolic abnormality (diabetes mellitus, insulin resistance, or hypertriglyceridemia). Metreleptin dose (once or twice daily) was titrated to a mean dose of 0.10 mg/kg/day with a maximum of 0.24 mg/kg/day. Means and changes from baseline to month 12 were assessed for glycated hemoglobin (HbA1c), fasting triglycerides (TGs), and fasting plasma glucose (FPG). Additional assessments included the proportions of patients achieving target decreases in HbA1c or fasting TGs at months 4, 12, and 36, medication changes, and estimates of liver size. Treatment-emergent adverse events (TEAEs) were recorded.


Significant mean reductions from baseline were seen at month 12 for HbA1c (–2.2%, n = 59) and FPG (–3.0 mmol/L, n = 59) and mean percent change in fasting TGs (–32.1%, n = 57) (all p ≤ 0.001). Reductions from baseline over time in these parameters were also significant at month 36 (all p < 0.001, n = 14). At month 4, 34.8% of patients had a ≥1% reduction in HbA1c and 62.5% had a ≥30% reduction in fasting TGs; at month 12, 80% of patients had a ≥1% decrease in HbA1c or ≥30% decrease in TGs, and 66% had a decrease of ≥2% in HbA1c or ≥40% decrease in TGs. Of those on medications, 41%, 22%, and 24% discontinued insulin, oral antidiabetic medications, or lipid-lowering medications, respectively. Mean decrease in liver volume at month 12 was 33.8% (p < 0.001, n = 12). Most TEAEs were of mild/moderate severity.


In patients with generalized lipodystrophy, long-term treatment with metreleptin was well tolerated and resulted in sustained improvements in hypertriglyceridemia, glycemic control, and liver volume.


Diabetes Insulin resistance Leptin Lipodystrophy Metreleptin 



All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript and take responsibility for the integrity of the work as a whole. Aegerion Pharmaceuticals provided funding for medical writing and/or editing support in the development of this manuscript; Jennifer L. Giel, Ph.D., of inScience Communications, Springer Healthcare (Philadelphia, PA, USA), based on input from authors, wrote the first draft and revised subsequent drafts of the manuscript, and Adrienne M. Schreiber of inScience Communications, Springer Healthcare (Philadelphia, PA, USA) copyedited and styled the manuscript per journal requirements. Aegerion Pharmaceuticals reviewed and provided feedback to the authors. The authors had full editorial control of the manuscript and provided their final approval of all content. Jean-Karl Sirois provided statistical analyses on behalf of Veristat LLC, Montreal, Canada, which was funded by Aegerion Pharmaceuticals, Inc. The authors acknowledge the services of the Clinical Core Laboratory of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health for measurement of leptin levels.


This work was supported by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases. E.A.O. is supported by NIH grant RO-1 DK-088114 as well as UM Lipodystrophy Fund donated by the Sopha Family and White Point Foundation of Turkey.

Compliance with ethical standards

Conflict of interest

E.A.O. has served as a consultant to Aegerion, Akcea, AstraZeneca, and Regeneron, received grants from Aegerion, Akcea, AstraZeneca, Gemphire, GIDynamics, and received non-material support from Aegerion and Boehringer Ingelheim. D.A.V. and D.B.S. have served as consultants to Aegerion Pharmaceuticals. A.L. and G.F. are employees of Aegerion Pharmaceuticals. T.S. is a former employee of Aegerion Pharmaceuticals. R.J.B., E.C., and P.G. declares that they have no conflict of interest.

Supplementary material

12020_2018_1589_MOESM1_ESM.pdf (17 kb)
Supplementary Information


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Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2018

Authors and Affiliations

  • Rebecca J. Brown
    • 1
  • Elif A. Oral
    • 2
  • Elaine Cochran
    • 1
  • David Araújo-Vilar
    • 3
  • David B. Savage
    • 4
  • Alison Long
    • 5
  • Gregory Fine
    • 5
  • Taylor Salinardi
    • 5
  • Phillip Gorden
    • 1
  1. 1.National Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthBethesdaUSA
  2. 2.Department of Internal MedicineUniversity of Michigan Medical School and Health SystemsAnn ArborUSA
  3. 3.Department of MedicineUniversity of Santiago de CompostelaSantiago de CompostelaSpain
  4. 4.The University of Cambridge Metabolic Research LaboratoriesWellcome Trust-MRC Institute of Metabolic ScienceCambridgeUK
  5. 5.Aegerion PharmaceuticalsCambridgeUSA

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