Through joint research with Daiichi Sankyo Co., Ltd., the research group of Yoji Minamishima, a specially appointed associate professor of the Institute of Biodefense Medicine, Kyushu University, and the Department of Medical Chemistry and Anesthesia, Keio University School of Medicine, is lethal of the diabetes drug metformin. It was clarified that a drug that activates a biological response to a hypoxic state (hypoxic response) is effective as a therapeutic agent for lactic acidosis, which is a side effect.
Metformin is the most commonly prescribed type 2 diabetes treatment in the world.In addition to lowering blood sugar, it is being reported that it has various effects such as suppressing the growth of cancer cells, lowering the carcinogenic rate, and prolonging the life span.Since it is old and the drug price is low, it is expected that the number of oral medications will continue to increase.However, there is a problem that "metformin-related lactic acidosis (MALA)", which has an extremely high case fatality rate of about 50% when taken orally by a person with impaired renal function, develops as a side effect.
This time, the research group focused on a drug (PHD inhibitor) that suppresses the enzymatic activity of proline hydroxylase PHD, which is an oxygen concentration sensor molecule.It was confirmed that this increased the expression of genes involved in glucose synthesis (gluconeogenesis) from lactic acid, and enhanced the uptake of blood lactic acid into the liver and kidneys.They found that this could dramatically improve the survival rate of mice with lactic acidosis.
This indicates that PHD inhibitors may be a silver bullet for lactic acidosis, which had only been treated as symptomatic treatment.
Paper information:[Molecular and Cellular Biology] Targeting oxygen sensing prolyl hydroxylase (PHD) for metformin-associated lactic acidosis treatment
