A Randomized Controlled Trial of Metformin on Left Ventricular Hypertrophy in Patients with Coronary Artery Disease without Diabetes: The MET-REMODEL Trial

Mohapradeep Mohan, Shaween Al-Talabany, Angela McKinnie, Ify Mordi, Jagdeep Singh, Stephen Gandy, Fatima Baig, Muhammad S . Hussain, U. Bhalraam, Faisel Khan, Anna Choy, Shona Matthew, Graeme Houston, Allan Struthers, J. George, Chim C. Lang (Lead / Corresponding author)

Research output: Contribution to journalArticle

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Abstract

AIM: We tested the hypothesis that metformin may regress left ventricular hypertrophy (LVH) in patients who have coronary artery disease (CAD), with insulin resistance (IR) and/or pre-diabetes.

METHODS AND RESULTS: We randomly assigned 68 patients (mean age 65 ± 8 years) without diabetes who have CAD with IR and/or pre-diabetes to receive either metformin XL (2000 mg daily dose) or placebo for 12 months. Primary endpoint was change in left ventricular mass indexed to height1.7 (LVMI), assessed by magnetic resonance imaging. In the modified intention-to-treat analysis (n = 63), metformin treatment significantly reduced LVMI compared with placebo group (absolute mean difference -1.37 (95% confidence interval: -2.63 to -0.12, P = 0.033). Metformin also significantly reduced other secondary study endpoints such as: LVM (P = 0.032), body weight (P = 0.001), subcutaneous adipose tissue (P = 0.024), office systolic blood pressure (BP, P = 0.022) and concentration of thiobarbituric acid reactive substances, a biomarker for oxidative stress (P = 0.04). The glycated haemoglobin A1C concentration and fasting IR index did not differ between study groups at the end of the study.

CONCLUSION: Metformin treatment significantly reduced LVMI, LVM, office systolic BP, body weight, and oxidative stress. Although LVH is a good surrogate marker of cardiovascular (CV) outcome, conclusive evidence for the cardio-protective role of metformin is required from large CV outcomes trials.

Original languageEnglish
Pages (from-to)3409-3417
Number of pages9
JournalEuropean Heart Journal
Volume40
Issue number41
Early online date17 Apr 2019
DOIs
Publication statusPublished - 1 Nov 2019

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Metformin
Left Ventricular Hypertrophy
Coronary Artery Disease
Randomized Controlled Trials
Insulin Resistance
Oxidative Stress
Biomarkers
Placebos
Body Weight
Blood Pressure
Intention to Treat Analysis
Thiobarbituric Acid Reactive Substances
Subcutaneous Fat
Glycosylated Hemoglobin A
Fasting
Magnetic Resonance Imaging
Confidence Intervals
Therapeutics

Keywords

  • Coronary artery disease
  • Insulin resistance
  • Left ventricular mass
  • Metformin
  • Oxidative stress
  • Pre-diabetes

Cite this

Mohan, Mohapradeep ; Al-Talabany, Shaween ; McKinnie, Angela ; Mordi, Ify ; Singh, Jagdeep ; Gandy, Stephen ; Baig, Fatima ; Hussain, Muhammad S . ; Bhalraam, U. ; Khan, Faisel ; Choy, Anna ; Matthew, Shona ; Houston, Graeme ; Struthers, Allan ; George, J. ; Lang, Chim C. / A Randomized Controlled Trial of Metformin on Left Ventricular Hypertrophy in Patients with Coronary Artery Disease without Diabetes : The MET-REMODEL Trial. In: European Heart Journal. 2019 ; Vol. 40, No. 41. pp. 3409-3417.
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abstract = "AIM: We tested the hypothesis that metformin may regress left ventricular hypertrophy (LVH) in patients who have coronary artery disease (CAD), with insulin resistance (IR) and/or pre-diabetes.METHODS AND RESULTS: We randomly assigned 68 patients (mean age 65 ± 8 years) without diabetes who have CAD with IR and/or pre-diabetes to receive either metformin XL (2000 mg daily dose) or placebo for 12 months. Primary endpoint was change in left ventricular mass indexed to height1.7 (LVMI), assessed by magnetic resonance imaging. In the modified intention-to-treat analysis (n = 63), metformin treatment significantly reduced LVMI compared with placebo group (absolute mean difference -1.37 (95{\%} confidence interval: -2.63 to -0.12, P = 0.033). Metformin also significantly reduced other secondary study endpoints such as: LVM (P = 0.032), body weight (P = 0.001), subcutaneous adipose tissue (P = 0.024), office systolic blood pressure (BP, P = 0.022) and concentration of thiobarbituric acid reactive substances, a biomarker for oxidative stress (P = 0.04). The glycated haemoglobin A1C concentration and fasting IR index did not differ between study groups at the end of the study.CONCLUSION: Metformin treatment significantly reduced LVMI, LVM, office systolic BP, body weight, and oxidative stress. Although LVH is a good surrogate marker of cardiovascular (CV) outcome, conclusive evidence for the cardio-protective role of metformin is required from large CV outcomes trials.",
keywords = "Coronary artery disease, Insulin resistance, Left ventricular mass, Metformin, Oxidative stress, Pre-diabetes",
author = "Mohapradeep Mohan and Shaween Al-Talabany and Angela McKinnie and Ify Mordi and Jagdeep Singh and Stephen Gandy and Fatima Baig and Hussain, {Muhammad S .} and U. Bhalraam and Faisel Khan and Anna Choy and Shona Matthew and Graeme Houston and Allan Struthers and J. George and Lang, {Chim C.}",
note = "The British Heart Foundation (grant number PG/14/4/30539). I.R.M is supported by a NHS Education for Scotland/Chief Scientist Office Post-Doctoral Clinical Lectureship (PCL 17/07). J.S.S.S is funded by European Foundation for the Study of Diabetes (EFSD) Research Fellowship grant.",
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A Randomized Controlled Trial of Metformin on Left Ventricular Hypertrophy in Patients with Coronary Artery Disease without Diabetes : The MET-REMODEL Trial. / Mohan, Mohapradeep; Al-Talabany, Shaween; McKinnie, Angela; Mordi, Ify; Singh, Jagdeep; Gandy, Stephen; Baig, Fatima; Hussain, Muhammad S .; Bhalraam, U.; Khan, Faisel; Choy, Anna; Matthew, Shona; Houston, Graeme; Struthers, Allan; George, J.; Lang, Chim C. (Lead / Corresponding author).

In: European Heart Journal, Vol. 40, No. 41, 01.11.2019, p. 3409-3417.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A Randomized Controlled Trial of Metformin on Left Ventricular Hypertrophy in Patients with Coronary Artery Disease without Diabetes

T2 - The MET-REMODEL Trial

AU - Mohan, Mohapradeep

AU - Al-Talabany, Shaween

AU - McKinnie, Angela

AU - Mordi, Ify

AU - Singh, Jagdeep

AU - Gandy, Stephen

AU - Baig, Fatima

AU - Hussain, Muhammad S .

AU - Bhalraam, U.

AU - Khan, Faisel

AU - Choy, Anna

AU - Matthew, Shona

AU - Houston, Graeme

AU - Struthers, Allan

AU - George, J.

AU - Lang, Chim C.

N1 - The British Heart Foundation (grant number PG/14/4/30539). I.R.M is supported by a NHS Education for Scotland/Chief Scientist Office Post-Doctoral Clinical Lectureship (PCL 17/07). J.S.S.S is funded by European Foundation for the Study of Diabetes (EFSD) Research Fellowship grant.

PY - 2019/11/1

Y1 - 2019/11/1

N2 - AIM: We tested the hypothesis that metformin may regress left ventricular hypertrophy (LVH) in patients who have coronary artery disease (CAD), with insulin resistance (IR) and/or pre-diabetes.METHODS AND RESULTS: We randomly assigned 68 patients (mean age 65 ± 8 years) without diabetes who have CAD with IR and/or pre-diabetes to receive either metformin XL (2000 mg daily dose) or placebo for 12 months. Primary endpoint was change in left ventricular mass indexed to height1.7 (LVMI), assessed by magnetic resonance imaging. In the modified intention-to-treat analysis (n = 63), metformin treatment significantly reduced LVMI compared with placebo group (absolute mean difference -1.37 (95% confidence interval: -2.63 to -0.12, P = 0.033). Metformin also significantly reduced other secondary study endpoints such as: LVM (P = 0.032), body weight (P = 0.001), subcutaneous adipose tissue (P = 0.024), office systolic blood pressure (BP, P = 0.022) and concentration of thiobarbituric acid reactive substances, a biomarker for oxidative stress (P = 0.04). The glycated haemoglobin A1C concentration and fasting IR index did not differ between study groups at the end of the study.CONCLUSION: Metformin treatment significantly reduced LVMI, LVM, office systolic BP, body weight, and oxidative stress. Although LVH is a good surrogate marker of cardiovascular (CV) outcome, conclusive evidence for the cardio-protective role of metformin is required from large CV outcomes trials.

AB - AIM: We tested the hypothesis that metformin may regress left ventricular hypertrophy (LVH) in patients who have coronary artery disease (CAD), with insulin resistance (IR) and/or pre-diabetes.METHODS AND RESULTS: We randomly assigned 68 patients (mean age 65 ± 8 years) without diabetes who have CAD with IR and/or pre-diabetes to receive either metformin XL (2000 mg daily dose) or placebo for 12 months. Primary endpoint was change in left ventricular mass indexed to height1.7 (LVMI), assessed by magnetic resonance imaging. In the modified intention-to-treat analysis (n = 63), metformin treatment significantly reduced LVMI compared with placebo group (absolute mean difference -1.37 (95% confidence interval: -2.63 to -0.12, P = 0.033). Metformin also significantly reduced other secondary study endpoints such as: LVM (P = 0.032), body weight (P = 0.001), subcutaneous adipose tissue (P = 0.024), office systolic blood pressure (BP, P = 0.022) and concentration of thiobarbituric acid reactive substances, a biomarker for oxidative stress (P = 0.04). The glycated haemoglobin A1C concentration and fasting IR index did not differ between study groups at the end of the study.CONCLUSION: Metformin treatment significantly reduced LVMI, LVM, office systolic BP, body weight, and oxidative stress. Although LVH is a good surrogate marker of cardiovascular (CV) outcome, conclusive evidence for the cardio-protective role of metformin is required from large CV outcomes trials.

KW - Coronary artery disease

KW - Insulin resistance

KW - Left ventricular mass

KW - Metformin

KW - Oxidative stress

KW - Pre-diabetes

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DO - 10.1093/eurheartj/ehz203

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