Randomized double‐blind placebo‐controlled study of leptin administration after gastric bypass

Abstract

Objective Obese individuals have high levels of circulating leptin and are resistant to the weight-reducing effect of leptin administration at physiological doses. Although Roux-en-Y gastric bypass (RYGB) is an effective weight loss procedure, there is a plateau in weight loss and most individuals remain obese. This plateau may be partly due to the decline in leptin resulting in a state of relative leptin insufficiency. The main objective of this study was to determine whether leptin administration to post-RYGB patients would promote further weight reduction. Design and Methods This was a randomized, double-blind, placebo-controlled cross-over study of 27 women who were at least 18 months post-RYGB and lost on average 30.8% of their pre-surgical body weight. Subjects received either leptin or placebo via subcutaneous injection twice daily for 16 weeks, then crossed over to receive the alternate treatment for 16 weeks. Results Weight change after 16 weeks of placebo was not significantly different from that after 16 weeks of leptin. No changes were observed in percent fat mass, resting energy expenditure, thyroid hormones, or cortisol levels. Conclusions Contrary to our hypothesis, we did not observe a significant effect of leptin treatment on body weight in women with relative hypoleptinemia after RYGB.

20 YEARS OF LEPTIN: Leptin in common obesity and associated disorders of metabolism

“…No difference in the weight change was observed between the groups at the end of 8 weeks of treatment. Furthermore, no changes were noted in either thyroid hormone or cortisol levels (Korner et al 2013).…”

Recombinant Human Leptin Does Not Alter Gut Hormone Levels after Gastric Bypass but May Attenuate Sweet Cravings

“…We previously reported that, contrary to our expectation, leptin administration did not lead to further weight loss in women who had undergone weight loss after RYGB and whose leptin levels were lower than that predicted for a nonreduced individual with the same BMI [32]. This paper examines our secondary objective, which was to establish whether leptin administration in this weight-reduced state would be associated with changes in hormones involved in nutrient metabolism as well as in satiation.…”

Metreleptin and generalized lipodystrophy and evolving therapeutic perspectives

“…In the first randomized placebo-controlled double-blind dose-escalation trial of 54 lean and 73 obese participants, significant weight loss was observed in obese participants on metreleptin versus placebo, with the greatest difference being 1.7 kg on placebo and 7.1 kg on 0.30 mg/ kg/d dosing [50]. Other trials, however, resulted in no significant effect of metreleptin on weight loss, though studies varied by population (weight, co-morbidities) [56], serum leptin concentration [66--68], and mode of weight loss [69]. On the other hand, the pramlintide/metreleptin study showed a synergistic effect on weight loss with~13% weight loss with dual therapy versus~5% weight loss with each drug alone [59].…”