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 presurgical 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.

Conclusion: Contrary to our hypothesis, we did not observe a significant effect of leptin treatment on body weight in women with relative hypoleptinemia after RYGB.

Figure 1

Plasma leptin levels during the course of study. A) Group P-L, received placebo followed by leptin; and B) Group L-P, received leptin followed by placebo. Actual leptin values are indicated in the table as mean ± SEM. *P < 0.01; **P < 0.001 compared with Wk 0 within group.

Figure 2

Change in body weight during 16 weeks of either placebo or leptin administration.