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Effects of Metformin on Microvascular Function and Exercise Tolerance in Women With Angina and Normal Coronary Arteries

A Randomized, Double-Blind, Placebo-Controlled Study

Sachin Jadhav, MD, William Ferrell, PhD, Ian A. Greer, MD, John R. Petrie, MD, PhD, Stuart M. Cobbe, MD and Naveed Sattar, MD, PhD^_*,_*

^_* BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow Royal Infirmary, Glasgow, Scotland
Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow, Scotland
Division of Developmental Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow, Scotland
Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, Scotland.

View larger version (15K): [in a new window]   Figure 1 The CONSORT (Consolidated Standards of Reporting Trial) diagram describing outcomes of all women within the study. 1Gastrointestinal side effects. 2There was 1 patient admitted with chest pain, 1 patient with gastrointestinal side effects, and 2 patients with nonspecific symptoms. ETT = exercise tolerance test.

View larger version (17K): [in a new window]   Figure 2 (A) Baseline and on-treatment (8 weeks) microvascular responses to acetylcholine (ACh) in the 16 women randomized to metformin (p = 0.0003, 2-way repeated measures analysis of variance [ANOVA]). (B) Baseline and on-treatment (8 weeks) microvascular responses to ACh in the 17 women randomized to placebo (p = 0.50, 2-way repeated measures ANOVA). (C) Baseline and on-treatment (8 weeks) microvascular responses to sodium nitroprusside (SNP) in the 16 women randomized to metformin (p = 0.46, 2-way repeated measures ANOVA). (D) Baseline and on-treatment (8 weeks) microvascular responses to SNP in the 17 women randomized to placebo (p = 0.95, 2-way repeated measures ANOVA).

View larger version (12K): [in a new window]   Figure 3 (A) Change over 8 weeks in microvascular responses to acetylcholine (ACh) in metformin and placebo groups (p < 0.0001, 2-way repeated measures analysis of variance [ANOVA]). (B) Change over 8 weeks in microvascular responses to sodium nitroprusside (SNP) in metformin and placebo groups (p = 0.55, 2-way repeated measures ANOVA).

View larger version (24K): [in a new window]   Figure 4 (A) Mean maximal ST-segment depression during exercise tolerance test (ETT) (mm) at baseline and on treatment (8 weeks) in the 33 women randomized to placebo (n = 17) or metformin (n = 16). (B) Median chest pain incidence before randomization and on treatment in the 33 women randomized to placebo (n = 17) or metformin (n = 16).