title: Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial.
abstract: BACKGROUND
  The protein hormone leptin is important to the homeostatic regulation of body weight. Treatment with exogenous leptin may affect weight loss.
  
  
  OBJECTIVE
  To determine the relationship between increasing doses of exogenous leptin administration and weight loss in both lean and obese adults.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled, multicenter, escalating dose cohort trial conducted from April 1997 to October 1998.
  
  
  METHODS
  Four university nutrition and obesity clinics and 2 contract clinical research clinics.
  
  
  METHODS
  Fifty-four lean (body mass index, 20.0-27.5 kg/m2; mean [SD] body weight, 72.0 [9.7] kg) and 73 obese (body mass index, 27.6-36.0 kg/m2; mean [SD] body weight, 89.8 [11.4] kg) predominantly white (80%) men (n = 67) and women (n = 60) with mean (SD) age of 39 (10.3) years.
  
  
  METHODS
  Recombinant methionyl human leptin self-administered by daily morning subcutaneous injection (0 [placebo], 0.01, 0.03, 0.10, or 0.30 mg/kg). In part A, lean and obese subjects were treated for 4 weeks; in part B, obese subjects were treated for an additional 20 weeks. Lean subjects consumed a eucaloric diet to maintain body weight at the current value, and obese subjects were prescribed a diet that reduced their daily energy intake by 2100 kJ/d (500-kcal/d) from the amount needed to maintain a stable weight.
  
  
  METHODS
  Body weight, body fat, and incidence of adverse events.
  
  
  RESULTS
  Weight loss from baseline increased with increasing dose of leptin among all subjects at 4 weeks (P = .02) and among obese subjects at 24 weeks (P = .01) of treatment. Mean (SD) weight changes at 4 weeks ranged from -0.4 (2.0) kg for placebo (n = 36) to -1.9 kg (1.6) kg for the 0.1 mg/kg dose (n = 29). Mean (SD) weight changes at 24 weeks ranged from -0.7 (5.4) kg for the 0.01 mg/kg dose (n = 6) to -7.1 (8.5) kg for the 0.30 mg/kg dose (n = 8). Fat mass declined from baseline as dose increased among all subjects at 4 weeks (P = .002) and among obese subjects at 24 weeks of treatment (P = .004); more than 95% of weight loss was fat loss in the 2 highest dose cohorts at 24 weeks. Baseline serum leptin concentrations were not related to weight loss at week 4 (P = .88) or at week 24 (P = .76). No clinically significant adverse effects were observed on major organ systems. Mild-to-moderate reactions at the injection site were the most commonly reported adverse effects.
  
  
  CONCLUSIONS
  A dose-response relationship with weight and fat loss was observed with subcutaneous recombinant leptin injections in both lean and obese subjects. Based on this study, administration of exogenous leptin appears to induce weight loss in some obese subjects with elevated endogenous serum leptin concentrations. Additional research into the potential role for leptin and related hormones in the treatment of human obesity is warranted.
authors.affiliation: Weight Control Unit, St Luke's-Roosevelt Hospital, New York, NY 10025, USA. SBH2@Columbia.edu
authors.forename: S B
authors.initials: SB
authors.lastname: Heymsfield
authors.forename: A S
authors.initials: AS
authors.lastname: Greenberg
authors.forename: K
authors.initials: K
authors.lastname: Fujioka
authors.forename: R M
authors.initials: RM
authors.lastname: Dixon
authors.forename: R
authors.initials: R
authors.lastname: Kushner
authors.forename: T
authors.initials: T
authors.lastname: Hunt
authors.forename: J A
authors.initials: JA
authors.lastname: Lubina
authors.forename: J
authors.initials: J
authors.lastname: Patane
authors.forename: B
authors.initials: B
authors.lastname: Self
authors.forename: P
authors.initials: P
authors.lastname: Hunt
authors.forename: M
authors.initials: M
authors.lastname: McCamish
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood; D001823:Body Composition; D015992:Body Mass Index; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D002149:Energy Intake; D005260:Female; D006801:Humans; D020738:Leptin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use; D016014:Linear Models; D008297:Male; D009765:Obesity / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D015431:Weight Loss
chemical_list: D000906:Antibodies; D020738:Leptin; D011994:Recombinant Proteins; C122136:recombinant methionyl human leptin