Targeting Accelerated Aging in COPD: The AMICO (A Trial of Metformin In COpd) Trial Design.

Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a disease of accelerated biological aging characterized by progressive lung function decline, emphysema progression and multiple age-related comorbidities. Current therapies improve symptoms and reduce exacerbations but have limited effects on disease progression. Metformin has demonstrated anti-aging properties through modulation of pathways involved in oxidative stress, inflammation, mitochondrial dysfunction and cellular senescence, making it a potential disease-modifying treatment in COPD.

AMICO (A Trial of Metformin In COPD) is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled phase III trial conducted in anonymous. A total of 212 patients with clinically stable COPD, centrilobular emphysema on computed tomography, post-bronchodilator FEV1 40%-70% predicted and accelerated FEV1 decline (>40 mL·year-1) will be randomized (1:1) to receive metformin (850 mg twice daily) or matching placebo for 36 months in addition to standard COPD treatment. Assessments include pulmonary function, chest computed tomography, exercise capacity, health status, muscle strength, body composition, age associated comorbidities development and aging-related biomarkers.The primary endpoint is the annual rate of FEV1 decline over 36 months. Secondary endpoints include emphysema progression, changes in diffusing capacity, COPD Assessment Test score, 6-minute walk distance, BODE index, handgrip strength, exacerbations, major cardiovascular events, cancer incidence and renal dysfunction.

AMICO is the first randomized trial specifically designed to evaluate metformin as a gerotherapeutic and disease-modifying intervention in COPD. The study may provide novel evidence supporting geroscience-based approaches to slow disease progression and improve long-term outcomes in patients with COPD.