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Table 1 Characteristics of the included studies (n = 9)

From: Effect of metformin on left ventricular mass and functional parameters in non-diabetic patients: a meta-analysis of randomized clinical trials

Author Year Study Design Follow up Intervention (mg) Control Cumulative dose Patient population Outcomes Sample size Randomized [E/C] Male% [E/C] Mean age [E/C] Country Outcome assessment
Ali [32] 2016 DB-RCT 4 months 500 × 2 Placebo 1000 STEMI patients LVEF (4 months), LVM, LVMI, and diastolic function (E, e′, E/e, and LAVI) 118/119 80.5/74.8 57.9/58.2 Netherlands 2D Echocardiography (Vivid 7)
Gupta [33] 2020 OL-RCT 12 months 1000 × 2 SOC 2000 Documented CAD (angiographically documented or a previous history of myocardial infarction/angina), verified HF functional class III, FIRI ≥ 2.5 by receiving basic therapy for CAD and CHF (HFrEF, HFmrEF and HFpEF) LVEF, Incidence of MI, hospitalization for HF decompensating, all-cause death, and conversion from Prediabetic to diabetes. secondary outcomes: QoL, (MLHFQ), neurohormonal, lipid profile, renal function, Insulin, aldosterone, and Nt-proBNP, 6 MWT 39/37 72.9/43.6 62/62 India Transthoracic echocardiography (iE33 xMATRIX | Philips)
Ladeiras-Lopes [15] 2021 OL-RCT 3, 6, and 12 months 1000 × 2 SOC 2000 Non-diabetic adults aged 40–65 years with non-diabetic MetS and diastolic dysfunction e′ velocity, LVEF, LVMI (g/m2), Pro-BNP, QoL (SF-36), CPX (Peak Vo2), FIRI, CRP 27/27 46/64 51.2/52.4 Portugal 2D Echocardiography
Larsen [16] 2020 DB-RCT 3 months 1000 × 2 SOC 2000 Insulin-resistant chronic HF patients without diabetes LVMI (g/m2), LVEF, QoL (MLHFQ), HBA1c, HOMA-IR, Pro-BNP, E/e ratio, GLS, Myocardial efficiency (WMI, MEE), CPX (resting and max Vo2), 6 MWT 19/17 89/71 68/61 Denmark 2D Echocardiography (Vivid E9 and E95, GE Healthcare, Horten, Norway)
Mohan [14] 2019 DB-RCT 12 months 1000 × 2 Placebo 2000 CAD with IR and/or pre-diabetes LVMI (g/m1.7), LVEF, Wt, TBA derivatives, Pro-BNP, A1C, HOMA-IR, systolic BP 31/32 84/75 64.5/64.5 UK Cardiac MRI (CMR)
Sardu [34] 2021 DB-RCT 12 months 850 × 2 Placebo 1700 Obese patients with pre-diabetes. All 83 patients underwent abdominoplastic surgery and, after treatment, received a hypocaloric diet inflammatory/oxidative stress, miRs’ expression, and cardiovascular function (LVMI and LVEF) 28/27 28.6/33.3 42.5/41.8 Italy 2D Echocardiography
Stakos [35] 2005 DB-RCT 12, and 24 months 500 mg × 1 Placebo 500 Non-diabetic patients with IR Insulin sensitivity, glucose tolerance, lipid profile, LVMI (g/m2), aortic distensibility, aortic PWV 59/97 24/26 40.5/41 Greece 2D Echocardiography M-Mode Echocardiography
Velázquez [18] 2016 OL-RCT Six months 850 × 1 SOC 850 35–60 years, diastolic dysfunction, abdominal obesity, and MS diagnosed according to the ATP III criteria. At least three of the five diagnostic criteria of MS Echocardiographic parameters, Lipid profile, BP, and CRP 20/20 46/46 44.5/44 Mexico 2D Echocardiography (Phillips model IE33)
Wong [17] 2012 DB-RCT 4 months 1000 × 2 Placebo 2000 Non-diabetic IR HF patients (FIRI ≥ 2.7) CPX (Peak Vo2 was the primary outcome), FIRI, VE/VCO2 slope, BNP, LVEF, 6-min walk test, MLHFQ 39/23 89.7/95.6 64/68 UK 2D Echocardiography
  1. E experimental group, C control group, BP blood pressure, CAD coronary artery disease, MS metabolic syndrome, CRP C reactive protein, CPX cardiopulmonary exercise testing, FIRI fasting insulin resistance index, HFrEF heart failure with reduced ejection fraction, HFmrEF heart failure with mid-range ejection fraction, HFpEF heart failure with preserved ejection fraction, IR insulin resistance, PWV pulse wave velocity, QoL quality of life, OL-RCT open-label randomized clinical trial; DB-RCT: Double-blinded randomized clinical trial, LAVI left atrial ventricular index, LVEF left ventricular ejection fraction, LVMI left ventricular mass index, SOC standard of care, TBA thiobarbituric acid derivatives