Effect of weight change and metformin on fibrinolysis and the von Willebrand factor in obese nondiabetic subjects: the BIGPRO1 Study. Biguanides and the Prevention of the Risk of Obesity.
Abstract
OBJECTIVE: Insulin resistance is associated with hypofibrinolysis. Metformin has been shown to improve insulin sensitivity and fibrinolysis. Its action on fibrinolysis and the von Willebrand factor was evaluated in the Biguanides and the Prevention of the Risk of Obesity (BIGPRO)1 trial in nondiabetic men (n = 151) and women (n = 306) aged between 34 and 65 years with a central fat distribution and a mean BMI of 32.5 kg/m2. RESEARCH DESIGN AND METHODS: The subjects were randomly allocated to a 1-year treatment with metformin (850 mg b.i.d.) or placebo, in addition to diet and exercise recommendations. RESULTS: Plasminogen activator inhibitor 1 (PAI-1) activity and antigen decreased significantly but similarly by 30 and 40%, respectively, in both the placebo and the metformin groups. This decrease occurred mainly in subjects who lost weight. Metformin did not have any significant additional effect on PAI-1. In contrast to the results for PAI-1, there was a significantly greater decrease in tissue-type plasminogen activator (tPA) antigen in the metformin than in the placebo group (mean+/-SD: -1.1+/-3.1 vs. 0.2+/-3.2 ng/ml, P < 0.02). The von Willebrand factor (vWF) also decreased significantly more in the metformin group (-0.17+/-0.42 vs. -0.05+/-0.38 U/I, P < 0.02). CONCLUSIONS: Weight loss was the main factor associated with the decrease in PAI-1, in accordance with the recent demonstration of production of PAI-1 by adipocytes. Metformin had a significant effect on two factors, tPA antigen and vWF, mainly secreted by the endothelial cells, which suggests an effect of the drug on the production or the metabolism of these two hemostatic proteins.
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Many different mechanisms beyond glycemic control have been implicated in vascular protection induced by metformin, including improvements in the inflammatory pathway, coagulation, oxidative stress and glycation, endothelial dysfunction, haemostasis, insulin resistance, lipid profiles, and fat redistribution.
“Many different mechanisms, beyond glycemic control, have been implicated in vascular protection induced by metformin such as improvements in the inflammatory pathway [86], coagulation [87], oxidative stress and glycation [88-92], endothelial dysfunction [88-90], haemostasis [88,91-93], insulin resistance improvement [94], lipid profiles [95,96], and fat redistribution [97,98].”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [93]
Plasma levels of plasminogen activator inhibitor and von Willebrand factor decrease with metformin therapy in non-diabetic subjects.
“Furthermore, plasma levels of PAI-1 and vWF, which are secreted mainly by the impaired endothelium, have been shown to decrease with metformin therapy in non-diabetic subjects [93].”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [93]
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BackgroundRole of clotting factors and fibrin structure in predisposition to atherothrombotic disease
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Díez, R., Garcia, J. J., Diez, M. J., Sierra, M., Sahagún, A. M., & Fernández, N. (2017) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-017-1809-x · Cited by 11 · see citing works
“Besides these important antidiabetic effects, which have been manifest utility in patients with type 2 diabetes [3] and in preventing it in patients with obesity and insulin resistance [4], metformin has actions on body weight [5], serum lipids level [6], blood pressure [7], vascular effect [8], nitroxidative and oxid…”
BackgroundThe Pharmacologic Basis for the Treatment of Endocrinopathic Laminitis
Durham, A. E. (2010) · Veterinary Clinics of North America Equine Practice · doi:10.1016/j.cveq.2010.04.006 · Cited by 9 · see citing works
The Cumulative Incidence and Risk Factors of Recurrent Venous Thromboembolism in the Elderly
Aleidan, F. A. S. (2020) · Vascular Health and Risk Management · doi:10.2147/vhrm.s264814 · Cited by 9 · see citing works
McCarty, M. F. (2004) · Medical Hypotheses · doi:10.1016/j.mehy.2004.03.038 · Cited by 9 · see citing works
Antidiabetes drug metformin is a donor of nitric oxide: EPR measurement of efficiency
Сереженков, В. А., Кузнецов, И. С., Romantsova, T. I., Кузнецова, М., & Vanin, A. F. (2011) · BIOPHYSICS · doi:10.1134/s0006350911060169 · Cited by 9 · see citing works
Metabolic complications of glucocorticoids – Prevention by metformin
Sanpawithayakul, K., & Korbonits, M. (2023) · Annales d Endocrinologie · doi:10.1016/j.ando.2023.05.002 · Cited by 8 · see citing works
Evaluation of the Association Metformin:Plantago ovataHusk in Diabetic Rabbits
Díez, R., Garcia, J. J., Diez, M. J., Sierra, M., Sahagún, A. M., Calle, Á. P., & Fernández, N. (2015) · Journal of Diabetes Research · doi:10.1155/2015/167526 · Cited by 6 · see citing works
Metformin plus oral contraceptive may decrease plasma sCD40 ligand in women with PCOS patients
Kebapçılar, L., Kebapçılar, A. G., Bilgir, O., Taner, C. E., Bozkaya, G., Yıldız, Y., & Sarı, İ. (2010) · Gynecological Endocrinology · doi:10.3109/09513590.2010.491164 · Cited by 6 · see citing works
“Plasma levels of PAI-1 and vWF, which are secreted mainly by impaired endothelium, have been shown to decrease with metformin therapy in non-diabetic subjects [21,22].”
BackgroundDiagnosis and Management of Horses with Equine Metabolic Syndrome (EMS)
Chameroy, K. A. (2010) · Cited by 3 · see citing works
- Authors
- Charles, M. A., Morange, P., Eschwège, E., André, P., Vague, P., & Juhan-Vague, I.
- Affiliations
- Inserm (FR)
- INSERM (National Institute of Health and Medical Research) Unit 21, Villejuif, France. charles@vjf.inserm.fr
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 1998-11-01
- Volume
- 21
- Issue
- 11
- Pages
- 1967-1972
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2054703675
- Cited by
- 120
- References
- 0
- Citations by year
- 2024: 3 · 2023: 2 · 2021: 1 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 4 · 2016: 1 · 2015: 3 · 2014: 4 · 2013: 5
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Blood properties and coagulation
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- metformin, weight loss, fibrinolysis, von Willebrand factor, plasminogen activator inhibitor-1, tissue plasminogen activator, obesity, insulin resistance, abdominal obesity, adipocytes, endothelial cells, hemostatic proteins
- MeSH terms
- Adult, Aged, Female, Fibrinolysis, Hemostasis, Humans, Hypoglycemic Agents, Insulin, Male, Metformin, Middle Aged, Obesity, Triglycerides, von Willebrand Factor, Weight Loss, Plasminogen Activator Inhibitor 1, Tissue Polypeptide Antigen
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