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/
m(2)) 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 p
arameters were measured before and after treatment. PEG-OB was generally we
ll tolerated based on adverse event reports, lab values, and vital signs. W
eekly sc PEG-OB led to sustained serum concentrations of PEG-OB and leptin
throughout treatment. No significant differences in the delta or percent we
ight loss, percent body fat, sleeping metabolic rate, or respiratory quotie
nt mere observed between the PEG-OB and placebo groups. Percent change in s
erum triglycerides from baseline was significantly correlated with body wei
ght 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 compar
ed with the placebo group, these differences were not statistically signifi
cant. 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 triglyceride
s suggest that a weekly 20-mg sc treatment with PEG-OB may have biological
effects in obese men.