According to new research published in Mayo Clinic Proceedings, dasatinib, a drug commonly used to treat certain types of leukemia, may have antidiabetic effects comparable to medications used to treat diabetes, and with more research, may become a novel therapy for diabetic patients.
Dasatinib is also used in the treatment of a specific type of chronic CML in children. Dasatinib is also used to treat a specific type of acute lymphoblastic leukemia in people who have outlived or are unable to take other leukemia medications due to side effects. Dasatinib belongs to a class of drugs known as kinase inhibitors. It works by preventing an abnormal protein from signaling cancer cells to multiply. This aids in the prevention of cancer cell spread.
Dasatinib is a tyrosine kinase inhibitor that is used to treat tumors, malignant tissue, and chronic myelogenous leukemia. Researchers from the Mayo Clinic and the University of the Connecticut School of Medicine wanted to know if dasatinib had any anti-diabetic properties in older patients with type 2 diabetes mellitus. Using a Mayo Clinic database containing over 9 million case histories spanning 25 years, they determined that it may have an anti-diabetic effect comparable to, if not greater than, current medications used to treat type 2 diabetes.
Our findings suggest that dasatinib or related senolytic drugs could become diabetic therapies. More research is needed to determine whether these findings are also seen in patients with type 2 diabetes mellitus who do not have an underlying malignancy.
Robert Pignolo
Diabetes is prevalent throughout the world, and there is concern that the diabetes mortality rate will rise. Various anti-diabetic drugs have been used in the past to improve the pathological condition of diabetes patients. Some diabetes medications have been shown to not only improve blood glucose levels but also to extend life. Acarbose, metformin, and sodium-glucose cotransporter 2 (SGLT2) inhibitors are examples of anti-diabetic drugs that can cause direct glucose excretion from the body.
The mechanism underlying the effect of these drugs is expected to involve a calorie restriction-mimicking effect via direct glucose excretion, rather than simply an effect that improves the disease state. According to the most recent findings, these anti-diabetic drugs have many health benefits that are not limited to the treatment of diabetes, i.e., these drugs may extend the life of people who do not have diabetes as well as those who do.
Dasatinib is a senolytic drug, a type of agent discovered at the Mayo Clinic that targets senescent cells in animal studies. These cells accumulate in many tissues with aging and at pathological sites in chronic diseases, and senolytic drugs appear to delay, prevent, or alleviate age-related changes, chronic diseases, and geriatric syndromes in animal studies.
“Our findings suggest that dasatinib or related senolytic drugs could become diabetic therapies,” says the study’s senior author, Robert Pignolo, M.D., Ph.D. “More research is needed to determine whether these findings are also seen in patients with type 2 diabetes mellitus who do not have an underlying malignancy.”
The Mayo Clinic’s Informatics for Integrating Biology at the Bedside framework was used by the researchers, which organizes and transforms patient records into a deidentified research database. The retrospective study began with a total of 9.3 million people being screened for the use of dasatinib or imatinib, another tyrosine kinase inhibitor approved for the treatment of a type of leukemia in 2001 but with limited senolytic activity. The records covered Mayo Clinic patients from 1994 to 2019. 279 of those patients were given imatinib and 118 were given dasatinib, and a total of 48 patients were included in the study after the further screening.
Dasatinib lowers serum glucose in patients with pre-existing type 2 diabetes more than imatinib and is comparable to first-line diabetic medications such as metformin and sulfonylureas, according to the findings.
More research is needed to determine whether dasatinib’s anti-diabetic effect is primarily due to its senolytic properties, according to Dr. Pignolo, director of the Translation and Pharmacology Program at Mayo Clinic’s Robert and Arlene Kogod Center on Aging. If this is the case, combining dasatinib with another senolytic drug, such as quercetin, may be more effective than dasatinib alone.
“This was really the first proof-of-concept that a senolytic drug could have significant long-term beneficial effects in humans,” says Dr. Pignolo. “According to animal model research, it is not necessary to give senolytic drugs continuously, so patients may only need to take a drug like dasatinib every few weeks, reducing potential side effects.”
