HRI activators to treat type 2 diabetes mellitus

Manuel Vázquez Carrera

Fundació Bosch i Gimpera, Universitat de Barcelona, Spain

The drugs currently available for the treatment of type 2 diabetes (DM2) have limited efficacy and tolerance, so that only a small percentage of patients achieve adequate control of the disease. For this reason, new drug therapies are needed to treat DM2.

FGF21 (Fibroblast growth factor 21) is a protein secreted by the liver with anti-diabetic effects. Several companies have developed FGF21 analogues that mimic the beneficial effects of this hormone. However, these analogues show some limitations (subcutaneous administration or excessive potency causing adverse effects). The use of drugs with oral bioavailability that increase the native production of FGF21 could avoid these problems.

Dr. Vazquez Carrera’s group has shown that the oral administration of a new class of compounds, HRI activators (Heme-Regulated eIF2α kinase) improve glucose intolerance, fatty liver and hypertriglyceridaemia in mice fed a high-fat diet. The development of this new class of HRI activator drugs could overcome the limitations of FGF21 analogues and provide a new therapeutic strategy to improve the morbimortality and quality of life of patients with DM2.