Table 1 This table summarizes the potential mechanisms through which GLP-1RA-associated miRNAs control cardiovascular diseases, hyperglycemia, and obesity in individuals with T2DM

Exenatide (BYDUREON™) + Metformin

Reduced anthropometric parameters, FBS, HbA1c, TC, LDL-C, CIMT; increased HDL-C, FMD

Upregulation of miR-27b

Correlated with adipokines (adiponectin, leptin, L-selectin)

[40]

Liraglutide + Metformin

Reduced FBS, HbA1c, TC, triglycerides, and LDL-C; no significant change in anthropometric parameters and HDL-C

Upregulation of miR-27b, miR-130a, and miR-210a

Anti-adipogenic effect of miR-27b via regulating glycerol-3-phosphate acyltransferase-1 and angiopoietin-like-3 genes; Targeting the ephrin-A3 (Efna3) and protein tyrosine phosphatase-1B (Ptp1b)

[42, 96, 97]

Liraglutide or Dulaglutide

Improved blood glucose control after one year

Upregulation of miR-378-3p and miR-126-3p linked to greater reductions in both HbA1c and fasting plasma glucose over treatment;

Upregulation of miR-21-5p, miR-24-3p, miR-223-3p, and miR-375-5p in patients meeting glycemic goals;

miR-375-5p as a predictor of HbA1c levels;

-

[28]

Liraglutide or Dulaglutide

Higher miR-15a levels associated with BMI, fasting glucose, HbA1c, insulinemia, HOMA-IR

Baseline levels of miR-15a-5p predict weight loss response in T2DM patients

-

[28]

Exendin-4

A Potential Biomarker

Downregulating miR-375 in diabetic animal models

-

[43]

Semaglutide

Reduction in body weight

Upregulating miR-5120;

Downregulating ABHD6

[47]

Liraglutide

Reduction in β-cell apoptosis

Downregulating miR-139-5p

To reduce β-cell apoptosis; affecting caspase-3 and Bcl-2; and linking GLP-1 signaling with IRS1 inhibition

[44]

Exendin-4

Maintains β-cell function; A biomarker for evaluating the β-cell cytoprotective efficacy of various antidiabetic treatments

Upregulating miR-375

To protect β-cells; the export of miR-375-3p to HDL is inversely regulated by insulin secretion

[43, 65]

Exendin-4

Enhances GLP-1R expression in islets

Downregulation of miR-204

MiR-204 is a regulator for thioredoxin-interacting protein (TXNIP)

[45]

Liraglutide in T2DM postmenopausal animal models

Improved bone quality

Upregulating specific exosomiRNAs related to bone-protective pathways;

affecting insulin secretion and Wnt signaling pathways

[50]

BYDUREON™ or liraglutide + metformin

Improved angiogenesis; Predictors of acute myocardial infarction and early atherosclerosis

Upregulating pro-angiogenic miRNAs, such as miRNA-27b, miRNA-130a, and miRNA-210a

Epigenetically regulated T2DM

[40, 42, 73,74,75,76]

Exenatide (long-acting)

Reduces diabetic cardiomyopathy

Upregulates miR-29b-3p in the myocardium,

Regulating Sarcolemma Associated Protein (SLMAP);

Reversal of miR-29b/SLMAP axis with GLP-1R inhibition

[48]

Liraglutide

Reduces endothelial cell apoptosis and promotes vascular protection; Reduces diabetic retinopathy

Downregulating miR-93-5p

To upregulate SIRT1 for protecting endothelial cells and reducing hyperglycemia

[46, 83]

Liraglutide

Reduces endothelial cell apoptosis

Under high-glucose conditions, it downregulates miR-34a-5p

To enhance the anti-apoptotic Bcl-2 protein

[46, 87]

Liraglutide

Reduces endothelial cell apoptosis in the aorta

Downregulating miR-181a-5p

To regulate the miR-181a-5p/CREB/BCL-2 pathway

[46, 91]

Exendin-4

Reduces micro-cardiovascular events induced by T2DM, such as diabetic kidney diseases and diabetic retinopathy

Inhibits the transmission of EV-miR-192 between healthy tubular epithelial cells under high-glucose stress;

To alleviate inflammation and angiogenesis in retinal cells subjected to high glucose levels by targeting ITGA1

[93,94,95]