Li and Laher included the
peroxisome proliferator-activated receptor d
modulator GW501516 among the potential
agents suggested as exercise mimetics.1 This
molecule was originally proposed as an exercise
mimetic drug in 2008,2 and immediately
after its discovery, questionable notices
publicized it as an “exercise in a pill” and
antiobesity agent. In combination with exercise,
GW501516 induced synergistically
fatigue-resistant type I fiber specification,
mitochondrial biogenesis, fatty acid oxidation,
and improved insulin sensitivity via
AMP-activated protein kinase (AMPK).3
Although the authors mentioned that
long-term animal studies with GW501516
increased neoplasia rates and reduced
lifespan, the pharmaceutical company
GlaxoSmithKline (GSK, Philadelphia, PA)
withdrew the clinical development of
GW501516 due to serious toxicities found
in routine, long-term animal and clinical
studies (ClinicalTrials.gov Identifier:
NCT00388180). Consequently, the
Investigational New Drug Application with
the US Food and Drug Administration was
then withdrawn in 2009 and no additional
investigations on this drug were conducted
by GSK. In fact, the World Anti-Doping
Agency has undertaken an unprecedented
decision to advise athletes about its toxicity
and thus ensure complete awareness of the
potential health risks, thus preventing
athletes from surrendering to temptation
of assuming GW501516 for performance
improvement. Accordingly, GW501516
should be clearly excluded as an exercise
mimetic due to its demonstrated
undesirable side-effects and ensuing health
risks.
