Selective Insulin Receptor Modulators (SIRM): A New Class of Antidiabetes Drugs?
- Endocrine Unit, Department of Clinical and Molecular Biomedicine, University of Catania, Garibaldi-Nesima Hospital, Catania, and IBB-CNR Catania section, Catania, Italy
- Corresponding author: Riccardo Vigneri, .
Diabetes is a complex disease that causes life-threatening complications and often requires life-long treatment. In the last few decades, drugs with different antidiabetes mechanisms have become available. These drugs include insulin-sensitizers (metformin and glitazones), secretagogues (sulphonylureas and incretins), and insulin-mimetics (both short- and long-acting analogs). These therapeutic tools have facilitated more tailored and efficacious therapy. When pancreatic insulin secretion is insufficient or absent, the injection of exogenous insulin or an insulin analog is the only available treatment to activate insulin receptors and restore the biological effects of insulin on target cells. This treatment, however, is associated with hypoglycemia, weight gain, and excess mitogenic activity that may promote the progression of pre-existing subclinical cancers. In these patients, an ideal treatment would activate the insulin receptor and replicate the beneficial metabolic actions of insulin, without causing adverse effects.
In an innovative approach to treatment of insulin-dependent diabetes, a study by Bhaskar et al. (1) in this issue of Diabetes introduces this type of drug. Using phage display technology, the authors identified a human monoclonal antibody (XMetA) that binds with high-affinity (ED50 0.10 nmol/L) to the insulin receptor (IR) and has full glucoregulatory activity as well as a reduced risk of hypoglycemia and weight gain. XMetA is a partial IR …