Leptin, an adipokine, regulates appetite, glucose and fat metabolism, and neuroendocrine function. A post-hoc pooled analysis of 4 studies (N=1064) in adults with BMI 27.0-40.0 kg/m2 showed that metreleptin (MTL), a leptin analogue, reduced weight in subgroups of adults with low baseline (BL) leptin levels (Fig. 1). A subsequent study (N=267) in adults with low BL leptin (females, ≤16 ng/mL; males, ≤5 ng/mL) and BMI 27.5-38.0 kg/m2 was conducted. Subjects (64% female; mean [SD] BL leptin, 14.2 [13.3] ng/mL) received QD subcutaneous MTL 10 mg, MTL 20 mg, or placebo. Both MTL doses decreased weight over time among subjects with low BL leptin (Fig. 2). MTL 20 mg showed statistically significant decreases by week 8. MTL was well tolerated. Thus, MTL 20 mg QD holds promise for weight loss among overweight and obese adults with low leptin levels.

A. DePaoli: Research Support; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp. A. Long: Employee; Self; Aegerion Pharmaceuticals. G.M. Fine: Employee; Self; Aegerion Pharmaceuticals. M. Stewart: Employee; Self; Novelion. Stock/Shareholder; Self; Novelion. S. O'rahilly: Advisory Panel; Self; Aegerion Pharmaceuticals, Pfizer Inc., AstraZeneca, MedImmune, Novo Nordisk Inc., ERX Pharmaceuticals, Inc..

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