Key result
Metformin reduces LVMI by ~9 g/m2 vs control in non-diabetic patients.
Why the study?
Left ventricular hypertrophy is associated with mortality in cardiovascular disease and metformin reduces left ventricular mass index in animal models, but its effects on LVMI and LVEF in non-diabetic patients required evidence synthesis.
Does metformin reduce left ventricular mass index and improve ejection fraction in non-diabetic patients with or without cardiovascular disease?
Meta-Analysis (n=754)
Does metformin reduce left ventricular mass index and improve ejection fraction in non-diabetic patients with or without cardiovascular disease?
Effect estimate: SMCC -0.5 (95% CI -0.84 to -0.16)
p-value: p=<0.01
Metformin therapy significantly regresses left ventricular mass index and modestly improves ejection fraction in non-diabetic patients, particularly at higher doses and in those with pre-existing heart failure.
Supports metformin for LV mass regression in non-diabetics; extends diabetic RCT data to broader CV populations.
Background Left ventricular hypertrophy is a common finding in patients with ischemic heart disease and is associated with mortality in patients with cardiovascular disease (CVD). Metformin, an antidiabetic drug, has been shown to reduce oxidative stress and left ventricular mass index (LVMI) in animal hypertrophy models. We summarized evidence regarding the effect of metformin on LVMI and LVEF. Methods Electronic databases were searched for randomized clinical trials (RCTs) that used metformin in non-diabetic patients with or without pre-existing CVD. The standardized mean change using change score standardization (SMCC) was calculated for each study. The random-effects model was used to pool the SMCC across studies. Meta-regression analysis was used to assess the association of heart failure (HF), metformin dose, and duration with the SMCC. Results Data synthesis from nine RCTs (754 patients) showed that metformin use resulted in higher reduction in LVMI after 12 months (SMCC = −0.63, 95% CI − 1.23; − 0.04, p = 0.04) and an overall higher reduction in LVMI (SMCC = −0.5, 95% CI − 0.84; − 0.16, p < 0.01). These values equate to absolute values of 11.3 (95% CI 22.1–0.72) and 8.97 (95% CI 15.06–2.87) g/m 2 , respectively. The overall improvement in LVEF was also higher in metformin users after excluding one outlier (SMCC = 0.26, 95% CI 0.03–0.49, P = 0.03) which translates to a higher absolute improvement of 2.99% (95% CI 0.34; 5.63). Subgroup analysis revealed a favorable effect for metformin on LVEF in patients who received > 1000 mg/day (SMCC = 0.28, 95% CI 0.04; 0.52, P = 0.04), and patients with HF (SMCC = 0.23; 95% CI 0.1; 0.36; P = 0.004). These values translate to a higher increase of 2.64% and 3.21%, respectively. Conclusion Results suggest a favorable effect for metformin on LVMI and LVEF in patients with or without pre-existing CVD. Additional trials are needed to address the long-term effect of metformin. Registration The study was registered on the PROSPERO database with the registration number CRD42021239368 ( https://www.crd.york.ac.uk/prospero ).
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Kamel et al. (2022) conducted a meta-analysis in Non-diabetic patients with or without pre-existing cardiovascular disease (n=754). Metformin vs. Standard of care or placebo was evaluated on Change in left ventricular mass index (LVMI) (SMCC -0.5, 95% CI -0.84 to -0.16, p=<0.01). Metformin therapy significantly reduced left ventricular mass index by an absolute value of 8.97 g/m2 (SMCC -0.5) compared to control in non-diabetic patients.
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