Metformin May Slow Emphysema Progression, Systemic Consequences

Therapy for emphysema primarily involves inhaled medications of limited systemic effect. However, metformin has demonstrated potential for slowing emphysema progression and its systemic consequences according to study results published in the American Journal of Respiratory and Critical Care Medicine.

Cigarette smoke inhalation can trigger oxidative stress and inflammation, which may lead to accelerated lung aging, apoptosis, and emphysema, as well as systemic pathologies. Metformin has been linked to a reduced risk of cancer and cardiovascular disease, suggesting a beneficial role in other diseases associated with aging. Therefore, researchers posited that use of metformin may ameliorate cigarette smoke-induced pathologies of emphysematous chronic obstructive pulmonary disease (COPD). To test this hypothesis, the researchers chronically exposed mice to cigarette smoke and fed them metformin for the second half of their exposure.

Researchers studied lung, kidney, and muscle pathologies, lung proteostasis, endoplasmic reticulum stress, mitochondrial function, and mediators of metformin effects in vivo and/or in vitro. To explore the impact of metformin in human disease, the researchers also evaluated the association of metformin use with indices of emphysema progression over 5 years of follow-up among the COPDGene Study participants. The association of metformin use with percent emphysema and adjusted lung density was estimated with a linear mixed model.

Metformin protected against cigarette smoke-induced pulmonary inflammation, airspace enlargement, and small airway remodeling, glomerular shrinkage, oxidative stress, apoptosis, telomere damage, aging, dysmetabolism in vivo and in vitro, and endoplasmic reticulum stress. The AMP-activated protein kinase (AMPK) pathway was central to the protective action of metformin. Among the COPDGene participants, individuals who took metformin compared with those who did not had slower progression of emphysema (P =.02) and adjusted lung density decrease (P =.01).

“Our results provide a rationale for clinical trials testing the efficacy of metformin in limiting emphysema progression and its systemic consequences,” concluded the study authors.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Polverino F, Wu TD, Rojas-Quintero J, et al. Metformin: experimental and clinical evidence for a potential role in emphysema treatment. Am J Respir Crit Care Med. Published online May 24, 2021. doi:10.1164/rccm.202012-4510OC