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Improved diastolic function in non-diabetic patients with metabolic syndrome treated with metformin: 1 year results from MET-DIME randomized clinical trial
Sub-topic : Echocardiography: Systolic and Diastolic Function
Session type : Poster Session
Authors : R Ladeiras-Lopes (Vila Nova de Gaia,PT), F Sampaio (Vila Nova de Gaia,PT), S Leite (Porto,PT), N Bettencourt (Porto,PT), A Leite-Moreira (Porto,PT), V Gama (Vila Nova de Gaia,PT), P Braga (Vila Nova de Gaia,PT), R Fontes-Carvalho (Vila Nova de Gaia,PT)
1Gaia Hospital Centre, Department of Cardiology - Vila Nova de Gaia - Portugal
2Faculty of Medicine, University of Porto - Porto - Portugal
Background: Metabolic syndrome (MetS) is highly prevalent and has a complex pathophysiology with insulin resistance as a key player. Furthermore, MetS is associated with preclinical diastolic dysfunction that impairs functional capacity and quality of life (QoL).
Purpose: This randomized trial was designed to evaluate if the addition of metformin to the standard treatment of non-diabetic patients with MetS improves diastolic dysfunction, functional capacity and QoL.
Methods: In this randomized, open-label, blinded-endpoint trial, 54 non-diabetic adults (40 to 65 years old) with MetS and diastolic dysfunction (mean e’<10.2 cm/s if 40-59 years old; mean e’<7.2 cm/s if 60-65 years old), were recruited. Patients were randomized to lifestyle counseling or lifestyle counseling plus metformin (target dose 1000 mg bid). Primary endpoint was improvement in mean e’ velocity (assessed at baseline, 6 and 12 months). Secondary endpoints were improvements in insulin resistance (HOMA-IR), functional capacity (peak oxygen uptake during cardiopulmonary exercise test), quality of life (using the SF-36 questionnaire). Linear mixed effects modelling was used for longitudinal data analysis.
Results: Fifty patients were included in this analysis (mean age=51.8±6.3; 54% males). Evaluating MetS criteria at baseline, all patients had elevated waist circumference (mean=105.1±9.6 cm), 92% were hypertensive, 58% had low HDL-cholesterol, 56% showed abnormal glucose homeostasis (median HOMA-IR=3.7, IQR 2.6-5.1) and 50% had elevated triglycerides. Metformin treatment was associated with a significant decrease in HOMA-IR at 1 year. Between-group change in the mean e’ velocity during the first year of follow-up was not significantly different in the intention-to-treat analysis (-0.34 cm/s in the control group vs +0.26 cm/s in the metformin group; p=0.132) but the difference was significant in the as-treated analysis (-0.52 cm/s in the control group vs +0.46 cm/s in the metformin group; p=0.009), adjusting for age, gender, baseline grade of diastolic dysfunction, treatment with modifiers of the renin-angiotensin-aldosterone axis and presence of symptoms of heart failure. During the 1-year follow-up there was no significant change in peak oxygen uptake (+0.1 mL/kg/min in the control group vs +0.8 mL/kg/min in the metformin group; p=0.401). In addition, there was a non-significant increase in mental component score of SF-36 (+4.83 points in the control group vs +2.17 points in the metformin group; p=0.173) and a significant increase in the physical component score of SF-36 (+3.75 points in the control group vs +4.75 points in the metformin group; p=0.023) that was not affected by treatment group.
Conclusion: In this pragmatic randomized trial, metformin treatment was associated with improved diastolic function in non-diabetic patients with MetS and diastolic dysfunction.
ESC 365 is supported by Bayer, Boehringer Ingelheim and Lilly Alliance, Bristol-Myers Squibb and Pfizer Alliance, Novartis Pharma AG and Vifor Pharma in the form of educational grants. The sponsors were not involved in the development of this platform and had no influence on its content.
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