Effect of the Tyrosine Kinase Inhibitors (sunitinib, sorafenib, dasatinib, and imatinib) On Blood Glucose Levels in Diabetic and Non-Diabetic Patients

• Published in: Blood Vol. 114; no. 22; p. 4265
• Main Authors: Agostino, Nicole M., Chinchilli, Vernon M, Koszyk-Szewczyk, Anita, Gingrich, Rebecca, Sivik, Jeff, Drabick, Joseph
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 20.11.2009
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V114.22.4265.4265

Abstract 4265 Tyrosine kinase is a key enzyme utilized in many intracellular messaging pathways. Understanding of the role of particular tyrosine kinases in various malignancies has allowed for the design of compounds, the tyrosine kinase inhibitors (TKIs), which can specifically target these enzymes and hence, interfere with downstream signaling. TKIs have proven to be very successful in the treatment of a wide variety of malignant diseases including chronic myeloid leukemia, Philadelphia chromosome positive acute lymphoblastic leukemia, renal cell carcinoma and gastrointenstinal stromal tumors. Given the widespread nature of tyrosine kinase as a target and the promiscuous nature of the various inhibitors, it would not be surprising that these drugs would have effects beyond the expected result of targeting merely the tyrosine kinase of interest. Scattered reports have suggested that these agents appear to affect blood glucose levels. We studied the blood glucose levels retrospectively in diabetic (19) and non-diabetic (82) patients treated with dasatinib (8), imatinib (39), sorafenib (23) and sunitinib (30). All 4 drugs resulted in statistically significant decreased blood glucose levels in both diabetic and non-diabetic patients that resolved with cessation of treatment. Mean decreases blood glucose values for both non-diabetic and diabetic patients for dasatinib were – 53 mg/dl, imatinib – 9 mg/dl, sorafenib – 12 mg/dl and sunitinib -14 mg/dl. While diabetic and non-diabetic patients had the same decreases in blood glucose, on average, blood glucose values overall were 40 mg/dl lower in non-diabetic patients than in diabetic patients on dasatanib and imatinib. Non-diabetics had an overall mean blood glucose value of 24 mg/dl lower than diabetic patients on sorafenib, and 15 mg/dl lower than diabetic patients on sunitinib. Diabetic patients required some modifications of their medications including cessation of insulin or other hypoglycemic agents. One diabetic patient developed symptomatic hypoglycemia on sunitinib. The mechanism for the hypoglycemic effect of these drugs is unclear, but of the 4 agents tested, c-kit is a common target. C-kit has been shown to play a role in pancreatic β-cell survival in mouse models, so it is unclear why an inhibitor of the c-kit tyrosine kinase would improve blood glucose levels. It is important for clinicians to keep the potentially hypoglycemic effects of these agents in mind in their patients since symptomatic hypoglycemia can occur and modification of hypoglycemic agents may be required. These results also suggest that inhibition of a tyrosine kinase, be it c-kit or some other undefined target, may improve diabetes mellitus and deserves further study as a potentially therapeutic option. No relevant conflicts of interest to declare.