Session: OR17-Diabetes: New Diagnostic & Treatment Modalities
Room 307 (Moscone Center)
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
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