Metformin May Lower Risk of Hospitalization, Mortality in Concurrent COPD, Diabetes

An antidiabetic medication may lower the risk of hospitalizations and death among patients with diabetes and chronic obstructive pulmonary disease (COPD), according to new study results published in Endocrine Connections.

Analyzing data from 8 studies, researchers found that metformin was associated with a 28% decreased risk of COPD-related hospitalizations (risk ratio [RR], 0.72, 95% CI, 0.53-0.98; I² = 89%) based on data from 4 studies and a 40% decrease in all-cause mortality (RR, 0.60, 95% CI, 0.36;1.01; I² = 69%) based on data from 3 studies.

The researchers noted that these improvements were seen without an increase in the risk of hyperlactatemia (RR, 1.14; 95% CI, 0.92-1.41; I² = 8%) based on data from 4 studies.

“Our study first provides significant statistical evidence to assess the effect and safety of metformin on the patients with concurrent diabetes and COPD, which guides the medical treatments in patients with concurrent diabetes and COPD,” explained the researchers. “Our meta-analysis demonstrates for the first time that the use of metformin in patients with concurrent diabetes and COPD is associated with lower COPD-related hospitalizations and the risk of all-cause mortality without increasing the risk of hyperlactatemia. These findings affirmed metformin’s active role in treatment for COPD.”

The researchers outlined several possibilities underlying metformin’s protective effect against COPD exacerbation in these patients, including the medication’s anti-inflammatory effect against a group of diseases characterized by increased inflammation and oxidative stress. A previous prospective study found that metformin increased inspiratory muscle strength by 11% in patients with moderate to severe COPD after 6 months of treatment, suggesting the medication can improve respiratory muscle function. The researchers also noted that insulin resistance, improved by metformin, is correlated with skeletal muscle dysfunction and inflammation in COPD.

The researchers noted the small number of studies included in their analysis and their retrospective observational nature, as well as heterogeneity among the studies, as limitations on their findings’ generalizability.

“We hypothesized that heterogeneity may be associated with severity of COPD and the duration of metformin administration. Unfortunately, most original studies did not describe the severity of COPD in the patients and we were unable to perform a subgroup analysis of it,” they wrote. “Regarding COPD-related hospitalizations, sensitivity analysis suggested that when the study by Fu-Shun Yen (2020) was excluded, heterogeneity decreased from 89% to 57% and RR changed from 0.72 to 0.57, with the results still being statistically significant. We suspect that because the study by Fu-Shun Yen (2020) had a longer follow-up (5.01 years) than the other 3 studies, the COPD-related hospitalizations were higher regardless of whether the patients were taking metformin or not, which might be one reason for the significant heterogeneity.”

The researchers also cited a possibility of publication bias due to an inability for assessment and subgroup analysis.

Reference

Liang Z, Yang M, Xu C, Zeng R, Dong L. Effects and safety of metformin in patients with concurrent diabetes mellitus and chronic obstructive pulmonary disease: a systematic review and meta-analysis. Endocr Connect. Published online August 22, 2022. doi:10.1530/EC-22-0289