Table 1.
Clinical studies of metformin in diabetic patients with cardiovascular risk.
| Subjects | Grouping | Results | Conclusion |
|---|---|---|---|
| T1DM who are at higher risk of CVD. | Metformin (1 g twice a day) + insulin (n=219) Placebo + insulin (n=219) |
↓the maximum cIMT ↓body weight and LDL cholesterol ↑eGFR |
Metformin may exhibit a greater effect in CVD risk management in patients with T1DM who are at higher risk of CVD (24). |
| Children with T1DM. | Metformin (1 g twice a day) + insulin (n=45) Placebo + insulin (n=45) |
↑GTN ↓insulin dose ↓HbA1c |
Metformin can improve HbA1c, the function of vascular smooth muscle and reduce insulin doses in children with T1DM (25). |
| T2DM | Metformin users (n = 7457) Non-users (n = 12 234) |
↓mortality rates (HR=0.76, 0.65-0.89; P<0.001) ↓mortality rates of patients with a history of congestive heart failure (HR=0.69, 0.54-0.90; P=0.006). |
Metformin treatment, as a means of secondary prevention, can reduce the mortality of diabetic patients (26). |
| Patients with T2DM and renal insufficiency. | Metformin users (n = 67749), Sulfonylureas (n = 28976) Weighted cohort metformin (n=24679), sulfonylureas (n=24799) |
↓MACE rates (adjusted HR=0.80, 95% CI, 0.75-0.86) | In diabetic patients with decreased renal function treated with monotherapy, metformin treatment reduced the risk of MACE compared with sulfonylureas (27). |
| T2DM | Metformin group (n=20) (500 mg twice a day) Gliclazide group (n=20) Pioglitazone group (n=20) |
↓LDL(3) mass and the LDL(3)-to-LDL ratio ↑HDL(2)-to -HDL(3) ratio |
Compared with gliclazide, the content of HDL and LDL subgroups in the pioglitazone or metformin group changed favorably.Such changes may be related to reducing the risk of AS (28). |
| Patients with IGT | 1645 pairs of matched samples (534 LSM, 558 metformin(850 mg twice daily) and 553 placebo). | LSM: ↑large HDL, ↓small HDL, small and dense LDL as well as large and buoyant VLDL Metformin: modestly ↑small and large HDL, ↓small and dense LDL |
LSM or metformin treatment has a good effect on lipoprotein subcomponents, which may delay the development of diabetes and AS (29). |
| Pre-DM | Placebo (n=1082) Metformin (850 mg twice daily) (n=1073) Lifestyle (n=1079) |
↓CAC severity and presence of men (CAC presence, 75% vs. 84%, CAC severity, 39.5 vs. 66.9 agatston units) | Metformin can prevent CAD in men with prediabetes and early diabetes (30). |
| HIV patients with MetS | No LSM (n=11), LSM (n=11), No LSM + metformin (n=13), LSM +metformin (n=15) (850 mg twice a day) |
↓CAC improved HOMA-IR LSM had no obvious effect on CAC progression |
These results show that metformin can prevent plaque progression in HIV-infected MetS patients (31). |
| First-degree relatives of T2DM patients with MetS | Placebo (n = 15) metformin (n = 16) (850 mg twice a day) | ↓body weight, BMI, FPG and systolic blood pressure Improved blood lipids and endothelium-dependent FBF. |
Metformin can improve the vascular endothelial function of first-degree relatives with MetS in patients with T2DM, regardless of the known hypoglycemic effect (32). |
| Patients with stable angina pectoris and NOCS diabetes. | 86 normal blood glucose (NG) subjects, 86 pre-DM subjects and 86 metformin-treated pre-diabetes (pre-DM +metformin) subjects (850 mg twice a day) |
↓percentage of endothelial LAD dysfunction ↓MACE (predicted by a multivariable logistic regression model) |
Metformin treatment can decrease the high risk of MACE in pre-DM patients via improving coronary endothelial dysfunction (33). |
| Patients with CAD, IR and/or pre-DM. | Placebo (n=34) Metformin (n=34) (2 g once a day) |
↓LVMI ↓LVM, office systolic blood pressure, subcutaneous adipose tissue, body weight, and thiobarbituric acid reactive substance concentrations (oxidative stress biomarkers) |
Metformin treatment obviously decreased LVMI, LVM, local systolic blood pressure, and body weight. Large trials of cardiovascular results require definitive evidence to prove the cardioprotective effects of metformin (34). |
In this table, we describe the role of metformin in clinical research on atherosclerotic diseases, including subjects, grouping, results and conclusions. ↑Represents increase or activation. ↓Represents to reducion or inhibition. The corresponding abbreviations are as follows: AS, atherosclerosis; BMI, body mass index; CAC, coronary artery calcification; cIMT, carotid intima-media thickness; CVD, cardiovascular disease; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; FBF, forearm blood flow; FPG, fasting blood glucose; GTN, glyceryl trinitrate-mediated dilatation; HIV, The human immunodeficiency virus; HDL, high-density lipoprotein; HOMA-IR, homeostatic model of assessment-insulin resistance; IGT, impaired glucose tolerance; IR, insulin resistance; LAD, left anterior descending coronary artery; LDL, low-density lipoprotein; LSM, lifestyle modification; LVH, left ventricular hypertrophy; LVM, left ventricular mass; LVMI, left ventricular mass indexed to height; MACE, major adverse cardiac events; MetS, metabolic syndrome; NG, normal blood glucose; NOCS, non-obstructive coronary artery stenosis; pre-DM, pre-diabetes; T1DM, type 1 diabetes;T2DM, type 2 diabetes.