Trial Registration: ClinicalTrials.gov Identifier: [HOME] NCT00375388
Long-term effects of metformin on endothelial function in type 2 diabetes: a randomized controlled trial
Article first published online: 16 SEP 2013
© 2013 The Association for the Publication of the Journal of Internal Medicine
Journal of Internal Medicine
Volume 275, Issue 1, pages 59–70, January 2014
How to Cite
Bethesda Diabetes Research Center, Hoogeveen; Academic Medical Center, Amsterdam; Bethesda Hospital, Hoogeveen; Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht; Clinical Laboratory, Bethesda Hospital, Hoogeveen, The Netherlands; FUCAM, Louvain Academy, Belgium; Clinical Research and Development, E. Merck, Amsterdam; Free University Medical Center, Amsterdam, The Netherlands. Long-term effects of metformin on endothelial function in type 2 diabetes: a randomized controlled trial. J Intern Med 2014; 275: 59–70., , , , , , , ,
- Issue published online: 12 DEC 2013
- Article first published online: 16 SEP 2013
- Accepted manuscript online: 26 AUG 2013 02:35AM EST
- Merck Serono
- Merck Sharp & Dohme
- Novo Nordisk
- cardiovascular disease outcome;
- endothelial function;
- HOME trial;
- type 2 diabetes
We investigated whether metformin can improve endothelial function and decrease inflammatory activity, and thereby decrease the risk of atherothrombotic disease.
Subjects and design
A randomized, placebo-controlled trial with a follow-up period of 4.3 years set in the outpatient clinics of three nonacademic hospitals (Hoogeveen, Meppel and Coevorden Hospitals, the Netherlands). A total of 390 patients with type 2 diabetes treated with insulin were included. Either metformin 850 mg or placebo (one to three times daily) was added to insulin therapy. Urinary albumin excretion and plasma levels of von Willebrand factor (vWf), soluble vascular adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), C-reactive protein (CRP) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured at baseline and after 4, 17, 30, 43 and 52 months.
Metformin significantly reduced levels of vWF, sVCAM-1, t-PA, PAI-1, CRP and sICAM-1, which, except for CRP, remained significant after adjustment for baseline differences in age, sex, smoking and severity of previous cardiovascular (CV) disease. No effects on urinary albumin excretion or sE-selectin were observed. The improvements in vWf and sVCAM-1 statistically explained about 34% of the reduction in the risk of CV morbidity and mortality associated with metformin treatment in this study.
Metformin is associated with improvement in some (vWF and sVCAM-1) but not all markers of endothelial function, which may explain why it is associated with a decreased risk of CV disease in type 2 diabetes.