Metformin in severe exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial

Abstract

BackgroundSevere exacerbations of COPD are commonly associated with hyperglycaemia, which predicts adverse outcomes. Metformin is a well-established anti-hyperglycaemic agent in diabetes mellitus, possibly augmented with anti-inflammatory effects, but its effects in COPD are unknown. We investigated accelerated metformin therapy in severe COPD exacerbations, primarily to confirm or refute an anti-hyperglycaemic effect, and secondarily to explore its effects on inflammation and clinical outcome.MethodsThis was a multicentre, randomised, double-blind, placebo-controlled trial testing accelerated metformin therapy in non-diabetic patients, aged ≥35 years, hospitalised for COPD exacerbations. Participants were assigned in a 2:1 ratio to 1 month of metformin therapy, escalated rapidly to 2 g/day, or matched placebo. The primary end point was mean in-hospital blood glucose concentration. Secondary end points included the concentrations of fructosamine and C reactive protein (CRP), and scores on the COPD Assessment Test and Exacerbations of Chronic Pulmonary Disease Tool.Results52 participants (mean (±SD) age 67±9 years) were randomised (34 to metformin, 18 to placebo). All were included in the primary end point analysis. The mean blood glucose concentrations in the metformin and placebo groups were 7.1±0.9 and 8.0±3.3 mmol/L, respectively (difference −0.9 mmol/L, 95% CI −2.1 to +0.3; p=0.273). No significant between-group differences were observed on any of the secondary end points. Adverse reactions, particularly gastrointestinal effects, were more common in metformin-treated participants.ConclusionMetformin did not ameliorate elevations in blood glucose concentration among non-diabetic patients admitted to hospital for COPD exacerbations, and had no detectable effect on CRP or clinical outcomes.Trial registration numberISRCTN66148745 and NCT01247870.

Reduced mortality from lower respiratory tract disease in adult diabetic patients treated with metformin

“…More recently, Tseng reported that the use of metformin was associated with approximately 40% lower risk of COPD . Yet, not all results are consistent: a recent multicentre, randomized, double‐blind, placebo‐controlled trial found no effect of metformin administration on glucose elevations during COPD exacerbations, inflammation or COPD assessment test . The trial was however small, including 52 participants randomized to receive either metformin (34 participants) or placebo (18 participants).…”

“…Previous studies have examined the association of metformin use with the development of asthma and/or COPD as well as the morbidity related to these conditions in diabetic patients . However, it is not known whether metformin use reduces CLRD mortality among in patients with T2D.…”

Transfer factor for carbon monoxide in patients with COPD and diabetes: results from the German COSYCONET cohort

“…In non-diabetic patients metformin did not ameliorate acute exacerbations [33], but exerted positive effects on symptoms, health status, inspiratory muscle function, lung hyperinflation and gas trapping in a prospective open-label study of moderate to severe COPD patients with diabetes and BMI > 25 kg/m 2 [34]. Possibly the beneficial effects of anti-diabetic drugs on the lung occur only in the presence of definite inflammatory lung disease such as COPD.…”

Drug repurposing to treat asthma and allergic disorders: Progress and prospects

“…Of 1332 patients with both diseases, one‐third were on metformin and those patients had a lower risk of asthma exacerbation and asthma‐related hospitalization, suggesting that this might be an effective treatment for this patient population . This result contrasted with data evaluating metformin in a randomized controlled trial to treat patients with chronic obstructive pulmonary disease (COPD), which found that metformin had no effect on the severity of COPD exacerbations, indicating that the positive effects may not extend to other lung diseases.…”