The effect of leptin, caffeine/ephedrine, and their combination upon visceral fat mass and weight loss


  • Author contribution: AGL analyzed the data, interpreted the data, searched the literature, generated the figures and wrote the manuscript. SRS and FLG designed the study and were awarded an investigator-initiated grant to support the study, collected the data, analyzed the data, interpreted the data, reviewed the literature, and edited the manuscript. KF collected the data, interpreted the data, reviewed the literature and edited the manuscript.

  • Funding agencies: This study was funded through an investigator-initiated grant from Amgen Pharmaceuticals to SRS and FLG.

  • Disclosure: AGL, FLG, and KF have no conflicts of interest to declare. SRS is a consultant to Amylin Pharmaceuticals, Arena Pharmaceuticals, Inc., AstraZeneca, BristolMeyersSquibb, Elcelyx, Five Prime Therapeutics, Inc., Eli Lilly and Company, NGM Pharma, Novo Nordisk A/S, Orexigen Therapeutics, Inc., Piramal Life Sciences, Takeda Pharaceuticals, and Zafgen. Amgen pharmaceuticals provided the leptin and an unrestricted grant to conduct the study.

  • CLINICAL TRIAL REGISTRY: This trial is registered at NCT01710722



To evaluate the effects of combination caffeine/ephedrine and leptin A-200 on visceral fat mass and weight loss over 24 weeks.

Design and Methods

In this randomized, double-blind, parallel-arm trial, 90 obese subjects received one of the three treatments for 24 weeks: 200 mg caffeine/20 mg ephedrine t.i.d. (CE), leptin A-200 (recombinant methionyl human Fc-leptin, 20 mg q.d.) (L), or combination leptin A-200 and caffeine/ephedrine (LCE). Outcomes included change in weight, visceral fat mass by computed tomography, lean mass and fat mass by dual energy X-ray absorptiometry.


Groups treated with CE and LCE lost significant amounts of weight (−5.9 ± 1.2% and −6.5 ± 1.1%, P < 0.05) and whole body fat mass (−9.6 ± 2.4% and −12.4 ± 2.3%, P < 0.05) compared to leptin only group. Only treatment with LCE significantly reduced visceral fat mass (−11.0 ± 3.3%, P < 0.05). There were no differences in lean mass between treatment groups.


Our study provides evidence that CE is a modestly effective weight loss agent and produces significant reductions in fat mass. Leptin A-200 was not effective in producing weight loss and did not have any significant additive or synergistic actions when combined with CE.