Abstract
We studied whether in patients with COPD the use of metformin for diabetes treatment was linked to a pattern of lung function decline consistent with the hypothesis of anti-aging effects of metformin. Patients of GOLD grades 1–4 of the COSYCONET cohort with follow-up data of up to 4.5 y were included. The annual decline in lung function (FEV1, FVC) and CO diffusing capacity (KCO, TLCO) in %predicted at baseline was evaluated for associations with age, sex, BMI, pack-years, smoking status, baseline lung function, exacerbation risk, respiratory symptoms, cardiac disease, as well as metformin-containing therapy compared to patients without diabetes and metformin. Among 2741 patients, 1541 (mean age 64.4 y, 601 female) fulfilled the inclusion criteria. In the group with metformin treatment vs. non-diabetes the mean annual decline in KCO and TLCO was significantly lower (0.2 vs 2.3, 0.8 vs. 2.8%predicted, respectively; p < 0.05 each), but not the decline of FEV1 and FVC. These results were confirmed using multiple regression and propensity score analyses. Our findings demonstrate an association between the annual decline of lung diffusing capacity and the intake of metformin in patients with COPD consistent with the hypothesis of anti-aging effects of metformin as reflected in a surrogate marker of emphysema.
Highlights
We studied whether in patients with chronic obstructive pulmonary disease (COPD) the use of metformin for diabetes treatment was linked to a pattern of lung function decline consistent with the hypothesis of anti-aging effects of metformin
We studied whether the intake of metformin in patients with type 2 diabetes and COPD was associated with the time course of lung function
When requiring complete data regarding GOLD grades 1–4, GOLD groups A–D, smoking status, pack-years, FEV1, forced vital capacity (FVC), TLCO and KCO, as well as including only patients with continuous metformin therapy over all visits, this resulted in a study population of n = 1541 patients, of whom n = 186, 392, 248 and 715 patients had data at their last visits V2–V5, respectively (Fig. S1, Table 1)
Summary
We studied whether in patients with COPD the use of metformin for diabetes treatment was linked to a pattern of lung function decline consistent with the hypothesis of anti-aging effects of metformin. A rationale for the present analysis was the previous finding in a cross-sectional analysis that COPD patients with diabetes mellitus had no worse carbon monoxide (CO) diffusing capacity than patients without diabetes[12], one should have expected lower values due to additional vascular damage from diabetes; surprisingly, there was even a tendency towards better values This might indicate an association between COPD phenotype (emphysema vs airway-dominated) and the risk for d iabetes[13], or potential protective effects of anti-diabetic medication against e mphysema[12]. We hypothesized that the beneficial effect of metformin might be manifest in a reduced decline of emphysema-related functional markers over time, especially CO diffusing capacity, in contrast to functional markers less closely linked to emphysema Based on these considerations, we studied whether the intake of metformin in patients with type 2 diabetes and COPD was associated with the time course of lung function. Data were obtained from COSYCONET (COPD and Systemic Consequences—Comorbidities Network), a large, multi-center cohort study of COPD patients, and the statistical tools comprised multiple regression analysis and propensity score matching
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