Effects of Metformin on Microvascular Function and Exercise Tolerance in Women With Angina and Normal Coronary Arteries
Open accessAbstract
Objectives This study sought to determine whether metformin improves vascular function or myocardial ischemia in nondiabetic subjects.Background Metformin prevents diabetes and may reduce coronary events in patients with diabetes, but effects on microvascular function and angina are not clear.Methods We conducted an 8-week double-blind, randomized, placebo-controlled study of metformin 500 mg twice a day in 33 nondiabetic women with a prior history of normal coronary angiography but two consecutive positive (ST-segment depression > or =1 mm) exercise tolerance tests. All parameters were measured at baseline and at 8 weeks, together with an in vivo assessment of forearm (skin) microvascular function using laser Doppler imaging combined with iontophoresis.Results In comparison with placebo (n = 17), metformin recipients (n = 16) showed significant reductions in weight and in homeostatic model assessment for insulin resistance (p < 0.05, intention to treat). Endothelium-dependent microvascular responses improved significantly with metformin (2-way repeated analysis of variance, p = 0.0003), but responses with placebo were unchanged (p = 0.50). A comparison of change in acetylcholine responses between metformin and placebo recipients was significant, whether analyzed by a 2-way analysis of variance (p < 0.0001) or change in area under curves (mean change +392 perfusion units, 95% confidence interval [CI] 20 to 764). Endothelium-independent responses were not altered. Maximal ST-segment depression (-0.84 mm, 95% CI -1.49 to -0.20, p = 0.013), Duke score (6.1 U, 95% CI 1.8 to 10.5, p = 0.008), and chest pain incidence (-0.11 episodes/day, 95% CI -0.22 to 0.00, p = 0.056) improved in metformin relative to placebo recipients.Conclusions Metformin may improve vascular function and decrease myocardial ischemia in nondiabetic women with chest pain and angiographically normal coronary arteries. Larger controlled trials of longer duration are warranted.
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In non-diabetic subjects with normal coronary arteriography but two consecutive positive exercise tolerance tests, an 8-week period on metformin improved maximal ST-segment depression, Duke score, and chest pain incidence compared with placebo.
“In non-diabetic subjects with normal coronary arteriography but also with two consecutive positive (ST depression > 1 mm) exercise tolerance test, an 8-week period on metformin improved maximal ST-segment depression, Duke score, and chest pain incidence compared with placebo [76].”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [76]
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- Authors
- Jadhav, S., Ferrell, W., Greer, I. A., Petrie, J. R., Cobbe, S. M., & Sattar, N.
- Affiliations
- Glasgow Royal Infirmary (GB)
- Ninewells Hospital (GB)
- Corresponding author
- Sattar, Naveed
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2006-09
- Volume
- 48
- Issue
- 5
- Pages
- 956-963
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W1538751400
- Cited by
- 157
- References
- 38
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 6 · 2023: 15 · 2022: 13 · 2021: 8 · 2020: 13 · 2019: 8 · 2018: 8 · 2017: 7 · 2016: 10 · 2015: 8 · 2014: 4 · 2013: 8 · 2012: 5
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart rate and cardiovascular health
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- metformin, angina pectoris, microvascular function, endothelial function, exercise tolerance, myocardial ischemia, non-diabetic women, normal coronary arteries, ST-segment depression, chest pain, insulin resistance, acetylcholine response
- MeSH terms
- Adult, Angina Pectoris, Double-Blind Method, Electrocardiography, Female, Humans, Hypoglycemic Agents, Insulin Resistance, Metformin, Middle Aged, Weight Loss, Exercise Tolerance, Myocardial Ischemia
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