Tyrosine kinase inhibitors under investigation for the treatment of type II diabetes

ABSTRACT

Introduction: Type 2 diabetes is characterized by hyperglycemia that is the result of β-cell failure in the setting of peripheral insulin resistance. It is estimated that greater than 300 million individuals worldwide have diabetes. Tyrosine kinase inhibitors (TKIs), which are used to treat a variety of cancers, appear to have antihyperglycemic effects.

Areas Covered: This review summarizes studies that have investigated the use of TKIs in animal models of diabetes. Additionally, the authors review case series describing the effects of TKIs on glucose levels in adults taking these drugs for FDA approved indications.

Expert opinion: Given the scope and size of the worldwide diabetes epidemic, reports of amelioration or possible cure of the disease warrant special attention. TKIs appear to lower glucose levels in some, but not all individuals. Multi-center prospective studies are needed in which patient with diabetes treated with TKI undergo phenotyping to identify responders versus non responders to allow for precision medicine.

KEYWORDS:

• tyrosine kinase inhibitors
• type 2 diabetes
• adults
• imatinib
• sunitinib
• dasatanib
• nilotinib

Financial and Competing Interests Disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Article highlights

• Tyrosine kinase inhibitors (TKI) have revolutionized the treatment of cancers with targeted therapy. Multiple case reports have shown amelioration or resolution of diabetes in patients with malignancies treated with TKIs.

• Animal models have alternatively shown antihyperglycemic effects are mediated through a reduction in insulin resistance, reduction in inflammation, or improved insulin secretion and insulin signaling.

• In mouse models, treatment with imatinib appears to reduce diabetic atherosclerosis.

• Large case series with humans have shown mixed results—attenuation, resolution, or worsening of hyperglycemia have been seen.

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