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Weekly Subcutaneous Pegylated Recombinant Native Human Leptin (PEG-OB) Administration in Obese Men

Nutrition and Toxicology Research Center, NUTRIM, University of Maastricht (C.J.H., W.H.M.S., M.S.W.-P.), 6200 MD Maastricht, The Netherlands; Hoffmann-La Roche, Inc. (A.R.F.), Nutley, New Jersey 07110; and Department of Food Science and Human Nutrition, Colorado State University (F.J.S., L.A.C.), Fort Collins, Colorado 80523

Address correspondence and requests for reprints to: Wim H. M. Saris, Nutrition and Toxicology Research Center "NUTRIM," Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. E-mail: w.saris{at}hb.unimaas.nl

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.

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