Enemies or weapons in hands: investigational anti-diabetic drug glibenclamide and cancer risk.
Gao R., Yang T., Xu W.
Epidemiological evidence suggests that diabetes is associated with elevated cancer risk through the actions of hyperglycemia, hyperinsulinemia and chronic inflammation. Metformin, a first-line medication for type 2 diabetes mellitus, arouses growing concerns on its anti-cancer effect. However, data regarding the effect of glibenclamide on tumor growth and cancer risk are less consistent, which may be a potential anti-cancer drug. Areas covered: In this review, we clarified probable underlying mechanisms in preclinical studies and reviewed epidemiological evidence on glibenclamide's cancer risk in clinical studies. Glibenclamide inhibited carcinogenesis through ATP-binding cassette protein super-family and ATP-sensitive potassium channels, while majority of clinical researches reported an increased or non-significant elevated cancer risk of glibenclamide users compared with metformin users. Other sulfonylureas and diarylsulfonylureas were also briefly introduced. Expert opinion: The inconsistency between the results of studies was probably ascribed to undiscovered mechanisms, confounding factors, inconsistent comparators and publication bias. Existing clinical trials were prone to be afflicted by time-related bias including immortal time bias, time-window bias, and time-lag bias. Glibenclimiade could be a promising and well-tolerated anti-neoplastic drug targeting ATP-binding cassette protein super-family and KATP channels, but its efficacy still needs to be proven in well-designed long-term randomized controlled clinical trials.