Reduced decline of lung diffusing capacity in COPD patients with diabetes and metformin treatment

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.

Figure 1

Annual changes in lung function measures. Unadjusted annual changes in lung function measures (mean and 95%-confidence intervals) for the two groups receiving either no metformin (light bars) or metformin as continuous therapy (dark bars). Units are %predicted relative to baseline (GLI). For adjusted values see Table 2.

Figure 2

Association of metformin with annual changes in lung function (mean and 95%-confidence intervals). The four panels refer to KCO, TLCO, FEV₁ and FVC, and the changes on the vertical axes are expressed as percent predicted at baseline. Positive values mean that the fall of the lung function measure (negative change) is reduced by the respective amount compared to the non-metformin group. Each panel shows three estimated effects, first from the regression analyses, then from the propensity score analyses using either full or genetic matching. As can be seen, the results were similar within each lung function measure and the pattern of statistically significant vs non-significant effects was the same. In addition, indicators for collinearity are given. Results for any metformin therapy as well as for TLCO were similar (see “Results” section and Tables S1, S2, S3).