Dasatinib a novel diabetic therapy for control of blood sugar and weight: Study
USA: Treatment of type 2 diabetes (T2D) patients with dasatinib for a year led to a greater reduction in body weight and blood sugar versus those treated with imatinib. Also, dasatinib treated patients required less total daily insulin. The findings, published in the Mayo Clinic Proceedings, indicate that dasatinib may have antidiabetic effects comparable to contemporary diabetic treatments and hence therefore may be considered for use as a novel diabetic therapy.
Type 2 diabetes is a chronic condition that affects an estimated 425 million people worldwide and leads to significant morbidity and mortality. Tyrosine kinase inhibitors (TKIs) are used for treating select malignant neoplasms. Imatinib was the first TKI approved for Philadelphia chromosome–positive chronic myelogenous leukemia in 2001. This was soon followed by other TKIs, such as dasatinib in 2006. Some case reports have suggested TKIs, primarily imatinib, may improve glycemic control or even lead to complete remission of T2D.
A subsequent retrospective cohort study of patients with (n=17) and without (n=61) T2DM reported that treatment with various TKIs (sunitinib, sorafenib, dasatinib, and imatinib) was associated with lower serum glucose levels.
Against the above background, Robert J. Pignolo, Department of Medicine and Kogod Center on Aging, Mayo Clinic, Rochester, MN, and colleagues aimed to evaluate the antidiabetic effects of the senolytic agent dasatinib in older patients with type 2 diabetes mellitus in a retrospective cohort study.
The study included enterprise-wide Mayo Clinic patients using. The antidiabetic outcomes (change in hemoglobin A1c value, serum glucose concentration, and diabetic medications) after 1 year of a strongly senolytic tyrosine kinase inhibitor, dasatinib (n=16), was compared with a weakly senolytic tyrosine kinase inhibitor, imatinib (n=32).
Based on the study, the researchers found the following:
· Relative to imatinib, patients treated with dasatinib had a mean reduction of 43.7 mg/dL in serum glucose concentration (to convert glucose values to mmol/L, multiply by 0.0555) and required 28.8 fewer total daily insulin units in the setting of a 4.8-kg relative weight loss (5.3% of total body weight).
· Linear regression analysis suggests that the relative difference in weight accounts for 8.4 mg/dL of the 43.7 mg/dL blood glucose value decrease, or 19.2%.
· Relative to imatinib, patients treated with dasatinib had a mean 0.80 absolute point reduction in hemoglobin A1c and required 18.2 fewer total daily insulin units in the setting of a 5.9-kg relative weight loss (6.3% of total body weight).
"Future studies are needed to determine whether these results are translatable to patients with type 2 diabetes mellitus without underlying malignant diseases and to determine whether the antidiabetic effects of dasatinib are due to its senolytic properties," the researchers wrote.
Reference:
The study titled, "Antidiabetic Effects of the Senolytic Agent Dasatinib," is published in the journal Mayo Clinic Proceedings.
DOI: https://www.mayoclinicproceedings.org/article/S0025-6196(21)00554-1/fulltext
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