title: Safety of Metformin in Patients with Chronic Obstructive Pulmonary Disease and Type 2 Diabetes Mellitus.
abstract: Type 2 diabetes mellitus (T2DM) is commonly associated with chronic obstructive pulmonary disease (COPD). Metformin is a valuable treatment for T2DM, and may offer additional benefits in COPD. However, due to its rare association with lactic acidosis, its safety in COPD is uncertain. We retrospectively identified patients with T2DM who had been admitted to hospital for COPD exacerbations. We compared those who were taking metformin with those who were not, with respect to their lactate concentration (primary endpoint) and survival (secondary endpoint). The study cohort (n = 130) had a mean (±standard deviation) age of 73.0 ± 9.8 years and 47 (36%) were female. Arterial blood gases were recorded in 120 cases: 88 (73%) were hypoxemic, 45 (38%) were in respiratory failure and 33 (28%) had respiratory acidosis. The 51 patients (39%) in the metformin group had a median (interquartile range) lactate concentration of 1.45 mmol/L (1.10-2.05) versus 1.10 mmol/L (0.80-1.50) in the non-metformin group (p = 0.012). Median survival was 5.2 years (95% CI 4.5-5.8) versus 1.9 years (1.1-2.6), respectively (hazard ratio 0.57; 95% CI 0.35-0.94). This remained significant in a multivariate model adjusted for measurable confounders. In conclusion, among patients with COPD at high risk for lactate accumulation, metformin therapy was associated with a minor elevation of lactate concentration of doubtful clinical significance. Metformin was associated with a survival benefit, but this must be interpreted cautiously due to possible effects from unmeasured confounders. Viewed collectively, the results suggest that COPD should not present a barrier to the investigational or clinical use of metformin.
authors.affiliation: a 1 Clinical Pharmacology, Institute of Infection and Immunity, St George's, University of London , London , UK.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Hitchings
authors.affiliation: a 1 Clinical Pharmacology, Institute of Infection and Immunity, St George's, University of London , London , UK.|b 2 Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust , London , UK.
authors.forename: John R H
authors.initials: JRH
authors.lastname: Archer
authors.affiliation: a 1 Clinical Pharmacology, Institute of Infection and Immunity, St George's, University of London , London , UK.|c 3 Charing Cross Hospital, Imperial College Healthcare NHS Trust , London , UK.
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Srivastava
authors.affiliation: a 1 Clinical Pharmacology, Institute of Infection and Immunity, St George's, University of London , London , UK.
authors.forename: Emma H
authors.initials: EH
authors.lastname: Baker
keywords: Type 2 Diabetes Mellitus; adverse drug reaction; lactic acid; metformin; obstructive pulmonary diseases; survival