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Title: The role of metformin as a novel treatment for exacerbations of chronic obstructive pulmonary disease
Author: Hitchings, Andrew William
ISNI:       0000 0004 5918 8124
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2015
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Background: Hyperglycaemia predicts adverse outcomes in patients admitted to hospital for exacerbations of chronic obstructive pulmonary disease (COPD). Metformin promotes euglycaemia but not hypoglycaemia, making it suitable for use in a pre-emptive anti-hyperglycaemic strategy. Aims: To investigate the effects of met form in in COPD exacerbations, in particular to confirm or refute a glucose-lowering effect. Ultimately, to determine whether a larger study powered for patient-centred outcomes is justified. Methods: First, a retrospective analysis of the association between metformin, lactate concentration and mortality in diabetic patients with COPD exacerbations. Second, a randomised, double-blind, placebo-controlled trial testing metformin in patients hospitalised for COPD exacerbations. Participants were assigned in a 2:1 ratio to 1 month of treatment with metformin, escalated rapidly to 2 g/day, or placebo. The primary endpoint was mean in-hospital blood glucose concentration, in respect of which 48 participants would provide 90% power to detect a 1.5- mmol/L difference. Secondary end points included other markers of glycaemia, inflammation, recovery, and safety and tolerability. Results: Among the 130 patients in the retrospective study, 51 (39%) were taking metformin. Metformin was associated with a slightly higher lactate concentration (median difference 0.40 mmol/L, 95% confidence interval [Cl] 0.10-0.60), but lower all-cause mortality (hazard ratio 0.57; Cl 0.35-0.94). In the clinical trial, 52 participants were randomised to metformin or placebo (allocation ratio 1.9:1). The mean (SO) blood glucose concentration was 7.1 (0.9) mmoljL in the metformin group and 8.0 (3.3) mmol/L in the placebo group (difference -0.9 mmoljL, Cl -2.1 to +0.3; P=0.273). There were no differences in the secondary endpoints. Adverse reactions, particularly gastrointestinal effects, were more common in metformin-treated participants. Conclusion: In patients hospitalised for COPO exacerbations, pre-emptive metformin therapy does not significantly lower blood glucose concentration. On this basis, a larger trial testing the effects of metformin on patient-centred outcomes in this setting is unwarranted.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available