Pleiotropic effects of hypoglycemic agents: implications in asthma and COPD

Diabetes mellitus (DM) is a complex multifactorial disease due to the interaction between environmental noxae and genetic predisposition. Furthermore, an increased association between DM, especially Type 2 diabetes mellitus (T2DM), and the onset of pulmonary function impairment with a bronchial hyperresponsiveness has been documented. DM is a risk factor for accelerated decline in FEV₁ and the development of asthma and COPD. The increased blood glucose concentrations along with higher levels of oxidative stress and inflammation can influence the pulmonary function and, since hypoglycemic drugs can act on these different defects we can hypothesize their direct effect on obstructive pulmonary diseases. Metformin, a biguanide, is the molecule having several evidences of its action on asthma and COPD in patients with T2DM. In this population, Metformin can ameliorate pulmonary outcomes reducing high glucose concentrations, inflammation through the activation of the AMP-activated protein kinase, leading to the decreased production of pro-inflammatory cytokines and blunting allergic eosinophilic airway inflammation. There are evidences of Pioglitazone role on asthma, since the activation of PPARγ Pioglitazone might inhibit the synthesis and release of pro-inflammatory cytokines. Indeed, Pioglitazone can improve symptoms associated with asthma reducing episodes of exacerbation and oral steroid prescription. Finally, randomized clinical trials using hypoglycemic agents on patients with asthma and COPD with and without DM should be proposed as well as the implementation of a new formulation of hypoglycemic agents to make it possible to administer it via aerosol.