Antidiabetic Effects of the Senolytic Agent Dasatinib

Mayo Clin Proc. 2021 Dec;96(12):3021-3029. doi: 10.1016/j.mayocp.2021.06.025. Epub 2021 Nov 9.

Abstract

Objective: To evaluate the antidiabetic effects of the senolytic agent dasatinib in older patients with type 2 diabetes mellitus.

Methods: This retrospective cohort study included enterprise-wide Mayo Clinic patients using Informatics for Integrating Biology at the Bedside from January 1994 through December 2019. 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).

Results: Relative to imatinib, patients treated with dasatinib had a mean reduction of 43.7 mg/dL (P=.005) in serum glucose concentration (to convert glucose values to mmol/L, multiply by 0.0555) and required 28.8 fewer total daily insulin units (P=.08) in the setting of a 4.8-kg relative weight loss (5.3% of total body weight; P=.045). 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 (P=.05) reduction in hemoglobin A1c and required 18.2 fewer total daily insulin units (P=.16) in the setting of a 5.9-kg relative weight loss (6.3% of total body weight; P=.06).

Conclusion: Dasatinib may have antidiabetic effects comparable to contemporary diabetic treatments and may be considered for use as a novel diabetic therapy. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose / analysis
  • Blood Glucose / drug effects
  • Dasatinib / therapeutic use*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Glycated Hemoglobin A / analysis
  • Glycated Hemoglobin A / drug effects
  • Glycemic Control
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Imatinib Mesylate / therapeutic use
  • Linear Models
  • Male
  • Middle Aged
  • Retrospective Studies
  • Senotherapeutics / therapeutic use*

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Senotherapeutics
  • hemoglobin A1c protein, human
  • Imatinib Mesylate
  • Dasatinib