OR17-1 Metreleptin Treatment for Metabolic Abnormalities Associated with Lipodystrophy: Achieving A1C and Triglyceride Targets

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR17-Diabetes: New Diagnostic & Treatment Modalities
Sunday, June 16, 2013: 11:15 AM-12:45 PM
Presentation Start Time: 11:15 AM
Room 307 (Moscone Center)
Rebecca J Brown*1, Karen Lutz2, Elaine Cochran3, Jim Pratt2, Stephan Miller2, Erich Blase2, Matthew Wintle2, Jean Lin Chan2 and Phillip Gorden1
1National Institutes of Health, Bethesda, MD, 2Amylin Pharmaceuticals, LLC, San Diego, CA, 3NIDDK, National Institutes of Health, Bethesda, MD
Lipodystrophies are rare inherited or acquired syndromes of adipose tissue loss in which leptin deficiency is the etiologic basis for metabolic abnormalities including insulin resistance, diabetes, and/or hypertriglyceridemia. In this study, we examined the effect of metreleptin (ML, a recombinant analog of human leptin) on achieving commonly accepted therapeutic targets for A1C and triglyceride (TG) reduction at a 12-month treatment time point.

Patients were enrolled in an ongoing, open-label study of metreleptin at the NIH (NCT00025883). Inclusion criteria were low leptin levels (<8 ng/mL in men, <12 in women) and one or more of: diabetes mellitus, fasting TG >200 mg/dL, or fasting insulin >30 mU/mL. As of a July 2011 data cut, treatment duration was 2 mo to 11 y including 64 patients treated for approximately 12 mo or more. This population (N=64; 83% female, 64% Caucasian) included pediatric (53% <18 y) and adult (47% ≥18 y) patients with various lipodystrophy (LD) subtypes (44% congenital generalized, 28% familial partial, 22% acquired generalized, 6% acquired partial). Mean (±SD) baseline (BL) A1C was 8.3±2.2% (range 4.5-13.7%), TG 1088±2202 mg/dL (range 49-12697 mg/dL), and serum leptin 2.6±2.7 ng/mL (range 0.3-12 ng/mL).

Of 38 patients with BL A1C >7%, 74% had a decrease in A1C ≥1%, 47% had a decrease in A1C ≥2%, and 40% reached a target A1C of ≤7%. Of 41 patients with BL TG >200 mg/dL, 54% had a decrease in TG ≥50% and 34% reached a TG target of ≤200 mg/dL. Of 12 patients with BL TG >1000 mg/dL, placing them at risk for pancreatitis, 92% had a decrease in TG ≥50% and 75% reached a TG level ≤1000 mg/dL.

Concomitant medications were generally kept stable, except to minimize risk of hypoglycemia or to simplify the regimen. Among 53 patients treated with antidiabetes medications at BL, 43% decreased or discontinued one or more of these medications by 12 mo. For the 26 patients using insulin, median dose decreased from 300 U/d at BL to 75 U/d, including 8 patients who discontinued insulin (from a BL median dose of 525 U/d). The most frequent adverse events assessed as related to treatment were fatigue (10.9%), hypoglycemia (9.4%), decreased weight (7.8%), and alopecia (6.3%).

Despite often severe metabolic derangements at baseline, a substantial proportion of LD patients were able to reach therapeutic targets or achieve clinically meaningful improvement in diabetes and/or hypertriglyceridemia with ML treatment, often while reducing antidiabetes medications.

Disclosure: KL: Employee, Amylin Pharmaceuticals. JP: Employee, Amylin Pharmaceuticals. SM: Employee, Amylin Pharmaceuticals. EB: Employee, Amylin Pharmaceuticals. MW: Employee, Amylin Pharmaceuticals. JLC: Employee, Amylin Pharmaceuticals. PG: Employee, Amylin Pharmaceuticals. Nothing to Disclose: RJB, EC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

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