Weight loss, insulin resistance, and study design confound results in a meta-analysis of animal models of fatty liver

The classical drug development pipeline necessitates studies using animal
models of human disease to gauge future efficacy in humans, however there
is a low conversion rate from success in animals to humans. Non-alcoholic
fatty liver disease (NAFLD) is a complex chronic disease without any
established therapies and a major field of animal research. We performed a
meta-analysis with meta-regression of 603 interventional rodent studies
(10,364 animals) in NAFLD to assess which variables influenced treatment
response. Weight loss and alleviation of insulin resistance were
consistently associated with improvement in NAFLD. Multiple drug classes
that do not affect weight in humans caused weight loss in animals. Other
study design variables, such as age of animals and dietary composition,
influenced the magnitude of treatment effect. Publication bias may have
increased effect estimates by 37-79%. These findings help to explain the
challenge of reproducibility and translation within the field of
metabolism.