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Abstract
Metformin is an antihyperglycemic used to treat type 2 diabetes mellitus (T2DM). Patients with T2DM are at increased risk of cardiovascular disease. We explored the association between metformin use and cardiovascular magnetic resonance (CMR) derived stress myocardial blood flow (MBF), myocardial perfusion reserve (MPR) and major adverse cardiovascular events (MACE; all cause death, MI, stroke, heart failure hospitalisation and coronary revascularisation) in patients with T2DM. Multi-centre study of patients with T2DM, and healthy controls, underwent quantitative myocardial perfusion CMR using an artificial intelligence supported process. Multivariable regression analysis, and cox proportional hazard models of propensity score weighted patients quantified associations between metformin use, MBF, MPR, all cause death and MACE. Analysis included 572 patients with T2DM (68% prescribed metformin) with median follow-up 851 days (IQR 935 − 765). Metformin use was associated with an increase of MPR of 0.12 [0.08–0.40], p = 0.004. There were 82 MACE events (14.3%) including 25 (4.4%) deaths of which 16 were in those not prescribed metformin (8.7%), compared to 9 in patients prescribed metformin (2.3%): adjusted hazard ratio 0.24 (95% CI 0.08–0.70, p = 0.009). MACE events were similar between groups. This multicentre, inverse probability weighting propensity score analysis study showed that in patients with T2DM, metformin use is associated with higher MPR and improved all cause survival.
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1 University of Leeds, Department of Biomedical Imaging Science, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, UK (GRID:grid.9909.9) (ISNI:0000 0004 1936 8403)
2 St Bartholomew’s Hospital, Barts Heart Centre, London, UK (GRID:grid.416353.6) (ISNI:0000 0000 9244 0345); University College London, Institute of Cardiovascular Science, London, UK (GRID:grid.83440.3b) (ISNI:0000 0001 2190 1201)
3 University of Leicester and the NIHR Leicester, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Department of Cardiovascular Sciences, Cardiovascular Biomedical Research Centre, Leicester, UK (GRID:grid.412925.9) (ISNI:0000 0004 0400 6581)
4 University College London, Institute of Cardiovascular Science, London, UK (GRID:grid.83440.3b) (ISNI:0000 0001 2190 1201); University College London, Division of Medicine, National Amyloidosis Centre, London, UK (GRID:grid.83440.3b) (ISNI:0000 0001 2190 1201)
5 University College London, Division of Medicine, National Amyloidosis Centre, London, UK (GRID:grid.83440.3b) (ISNI:0000 0001 2190 1201); Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), University of Trieste, Centre for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Trieste, Italy (GRID:grid.5133.4) (ISNI:0000 0001 1941 4308)
6 St Bartholomew’s Hospital, Barts Heart Centre, London, UK (GRID:grid.416353.6) (ISNI:0000 0000 9244 0345); University College London, Institute of Cardiovascular Science, London, UK (GRID:grid.83440.3b) (ISNI:0000 0001 2190 1201); Carol Davila University of Medicine and Pharmacy, Bucharest, Romania (GRID:grid.8194.4) (ISNI:0000 0000 9828 7548)
7 National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, USA (GRID:grid.279885.9) (ISNI:0000 0001 2293 4638)
8 University of Leeds, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, UK (GRID:grid.9909.9) (ISNI:0000 0004 1936 8403); University of Leeds, Leeds Institute for Data Analytics, Leeds, UK (GRID:grid.9909.9) (ISNI:0000 0004 1936 8403)
9 University of Leeds, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, UK (GRID:grid.9909.9) (ISNI:0000 0004 1936 8403); University of Leeds, Leeds Institute for Data Analytics, Leeds, UK (GRID:grid.9909.9) (ISNI:0000 0004 1936 8403); Leeds Teaching Hosptislas NHS Trust, Department of Cardiology, Leeds, UK (GRID:grid.415967.8) (ISNI:0000 0000 9965 1030)