Dextromethorphan, an over-the-counter cough suppressant, and its metabolites may improve diabetic complications in mice and humans, according to research published this week in Nature Medicine. These results suggest a potential adjunct treatment for Type 2 diabetes.
Type 2 diabetes is marked by insufficient insulin secretion and elevated glucose levels in the blood. Commonly prescribed antidiabetic drugs cannot slow the progression of the disease and can lead to extremely low blood sugar levels, which can be life-threatening. Dextromethorphan is an active ingredient, with few adverse side effects, found in many over-the-counter cough medications and it acts by inhibiting N-Methyl-D-Aspartate (NMDA) receptors. These receptors are expressed in tiny clusters of insulin-producing beta cells in the pancreas, but their physiological role has not been clear.
Eckhard Lammert and colleagues found that genetic deletion of a key part of this class of receptors, or their pharmacological inhibition by drugs such as dextromethorphan, results in more potent glucose-stimulated insulin secretion in a sample of normal mouse and human pancreatic tissue.
These results, as well as improved glucose control, were also observed in a mouse model of Type 2 diabetes on administration of dextromethorphan. In a small, phase 2a, clinical trial involving 20 men with Type 2 diabetes, the authors also found that dextromethorphan increased serum insulin concentrations and lowered blood glucose.