Effect of the tyrosine kinase inhibitors (sunitinib, sorafenib, dasatinib, and imatinib) on blood glucose levels in diabetic and nondiabetic patients in general clinical practice

Abstract

Tyrosine kinase is a key enzyme activity utilized in many intracellular messaging pathways. Understanding the role of particular tyrosine kinases in malignancies has allowed for the design of tyrosine kinase inhibitors (TKIs), which can target these enzymes and interfere with downstream signaling. TKIs have proven to be successful in the treatment of chronic myeloid leukemia, renal cell carcinoma and gastrointestinal stromal tumor, and other malignancies. Scattered reports have suggested that these agents appear to affect blood glucose (BG). We retrospectively studied the BG concentrations in diabetic (17) and nondiabetic (61) patients treated with dasatinib (8), imatinib (39), sorafenib (23), and sunitinib (30) in our clinical practice. Mean declines of BG were dasatinib (53 mg/dL), imatinib (9 mg/dL), sorafenib (12 mg/dL), and sunitinib (14 mg/dL). All these declines in BG were statistically significant. Of note, 47% (8/17) of the patients with diabetes were able to discontinue their medications, including insulin in some patients. Only one diabetic patient developed symptomatic hypoglycemia while on sunitinib. The mechanism for the hypoglycemic effect of these drugs is unclear, but of the four agents tested, c-kit and PDGFRβ are the common target kinases. Clinicians should keep the potential hypoglycemic effects of these agents in mind; modification of hypoglycemic agents may be required in diabetic patients. These results also suggest that inhibition of a tyrosine kinase, be it c-kit, PDGFRβ or some other undefined target, may improve diabetes mellitus BG control and it deserves further study as a potential novel therapeutic option.

Tyrosine Kinase Inhibitor Sunitinib Allows Insulin Independence in Long-standing Type 1 Diabetes

“…Sunitinib, a tyrosine kinase inhibitor (TKI), along with other TKIs, is reported to lower blood glucose in type 2 diabetes and in recent-onset type 1 diabetes (T1D) (1,2). We report a case of sunitinib apparently inducing remission in longstanding T1D.…”

Efficacy of everolimus in patients with metastatic insulinoma and refractory hypoglycemia

“…Finally, beneficial effects with peptide receptor radionuclide therapy have been demonstrated in some patients with malignant insulinomas (37) as well as surgery including liver transplantation in anecdotal cases (5,31,37,38). Although sunitinib has recently been approved in progressive advanced pNET, the decline in blood glucose reported with this agent makes its use in malignant insulinoma questionable (37,39).…”

Diagnosis and Treatment of Insulinomas in the Adults

“…However hypoglycaemia appears to be rare with such medications, unless employed in combination with other medications or in patients with underlying diseases. Recently tyrosine kinase inhibitors were found to decrease plasma glucose concentrations (Agostino et al 2010). Patients with huge non functional endocrine tumours and multiple liver metastases may be at risk of developing hypoglycaemia when treated by long-acting somatostatin analogues, as a result of reduced glucagon and GH secretion, impairment of hepatic glucose output and delay in intestinal absorption of carbohydrates (Unek et al 2009).…”