Weekly subcutaneous pegylated recombinant native human leptin (PEG-OB) administration in obese men

• Published in: The journal of clinical endocrinology and metabolism 2000-11, Vol.85 (11), p.4003-4009
• Main Authors: HUKSHORN, Chris J, SARIS, Wim H. M, WESTERTERP-PLANTENGA, Margriet S, FARID, Adrienne R, SMITH, Francoise J, CAMPFIELD, L. Arthur
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biological and medical sciences; Body Composition - drug effects; Double-Blind Method; Energy Metabolism - drug effects; General and cellular metabolism. Vitamins; Humans; Leptin - adverse effects; Leptin - blood; Leptin - therapeutic use; Male; Medical sciences; Middle Aged; Obesity - blood; Obesity - drug therapy; Obesity - physiopathology; Pharmacology. Drug treatments; Placebos; Recombinant Proteins - administration & dosage; Recombinant Proteins - adverse effects; Recombinant Proteins - therapeutic use; Safety; Time Factors; Triglycerides - blood
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.85.11.4003

To assess the biological activity and tolerability of pegylated recombinant native human leptin (PEG-OB), 30 obese men (mean body mass index, 33.9 kg/m2) were randomized to a double-blind treatment with weekly sc injections of 20 mg PEG-OB or placebo for 12 weeks, in addition to a hypocaloric diet (deficit, 2 MJ/day). Body composition, energy expenditure, and metabolic parameters were measured before and after treatment. PEG-OB was generally well tolerated based on adverse event reports, lab values, and vital signs. Weekly sc PEG-OB led to sustained serum concentrations of PEG-OB and leptin throughout treatment. No significant differences in the delta or percent weight loss, percent body fat, sleeping metabolic rate, or respiratory quotient were observed between the PEG-OB and placebo groups. Percent change in serum triglycerides from baseline was significantly correlated with body weight loss in the PEG-OB group, but not in the placebo group. Although larger reductions in serum triglycerides were observed in the PEG-OB group compared with the placebo group, these differences were not statistically significant. We concluded that weekly injection of PEG-OB leads to sustained serum concentration of PEG-OB and leptin throughout the 12-week treatment period and is generally well tolerated. The trends observed in serum triglycerides suggest that a weekly 20-mg sc treatment with PEG-OB may have biological effects in obese men.