Title:Pioglitazone, Bladder Cancer, and the Presumption of Innocence
Volume: 17
Issue: 4
Author(s): Georgios S. Papaetis
Affiliation:
Keywords:
Pioglitazone, thiazolidinediones, bladder cancer, diabetes mellitus, insulin resistance, pharmacoepi demiology.
Abstract:
Background: Thiazolidinediones are potent exogenous agonists of PPAR-γ that
augment the effects of insulin to its cellular targets, mainly at the level of adipose tissue.
Pioglitazone, the main thiazolidinedione in clinical practice, has shown cardiovascular and renal
benefits in patients with type 2 diabetes, durable reduction of glycated hemoglobulin levels,
important improvements of several components of the metabolic syndrome, and beneficial effects
of non-alcoholic fatty liver disease.
Objective: Despite all of its established advantages, the controversy for an increased risk of
developing bladder cancer, combined with the advent of newer drug classes that achieved major
cardiorenal effects, have significantly limited its use spreading a persistent shadow of doubt for its
future role.
Methods: Pubmed, Google, and Scope databases have been thoroughly searched, and relevant
studies were selected.
Results: This paper thoroughly explores both in vitro and in vivo (animal models and humans)
studies that investigated the possible association of pioglitazone with bladder cancer.
Conclusion: Currently, the association of pioglitazone with bladder cancer cannot be based on
solid evidence. This evidence cannot justify its low clinical administration, especially in the
present era of individualised treatment strategies. Definite clarification of this issue is imperative
and urgently anticipated from future high quality and rigorous pharmacoepidemiologic research,
keeping in mind its unique mechanism of action and its significant pleiotropic effects.
