Table 1.

List of the main glucose-lowering medications and their mechanisms of action for Type 2 Diabetes and implicated in cardiovascular outcome trial (CVOT).

Class Drug	Agent	Administration	Mechanism of Action	Reference
Biguanides	Metformin	oral	↑ Insulin sensitivity by activating Adenosine Mono Phosphate-activated protein kinase (AMP-k) ↓ Hepatic glucose production	[2]
Thiazolidinediones	Pioglitazone	oral	↑ Insulin sensitivity by activation of Peroxisome Proliferator Activated Receptor gamma (PPAR-γ) ↓ Peripheral glucose uptake	[4,5,6]
Sulfonylureas	Glimepiride Gliclazide	oral oral	↑ Insulin secretion	[1,5]
Insulin	Glargine Degludec	injective	↑ Glucose disposal ↓ Hepatic glucose production	[7,8]
Dipeptidyl Peptidase-4 Inhibitors (DPP4-is)	Sitagliptin Linagliptin Omarigliptin	Oral oral oral	↓ Half-life and promoting the insulinotropism of Glucagon Like Peptide-1(GLP-1) ↑ Insulin secretion (glucose-dependent) ↓ Glucagon secretion (glucose-dependent) Enzymatic activities against chemotactic molecules and hormones modulating the intricate inflammatory, vascular and immune processes Improving glycemic control ↓ Total cholesterol and triglyceride levels Improve weight neutrality ↓ Risk factors Ameliorating cardiac function and vascular repair Block cleavage of many circulating peptides	[9,10]
Glucagon Like Peptide-1 Receptor Agonists (GLP-1RAs)	Liraglutide Exenatide Semaglutide Lixisenatide Albiglutide Dulaglutide	Injective Injective oral / injective Injective Injective Injective	↑ Insulin secretion (glucose-dependent) ↑ ß-cell proliferation ↑ Insulin biosynthesis ↓ ß-cell apoptosis ↓ Glucagon secretion (glucose-dependent) from pancreatic α-cells ↓ Rate of endogenous glucose production ↓ Gastric emptying ↑ Satiety ↓ Food intake ↓ Weight loss Improved blood pressure ↑ Control of cholesterol/dyslipidemia ↑ Low Density Lipoproteins particles oxidised (ox-LDL) ↓ Carotid Intima Media Thickness (CIMT) ↓ Flow-Mediated Dilation (FMD) ↓ Artery endothelial dysfunctions ↓ Atherosclerotic risk factors direct effects on both plaque initiation/formation and progression	[11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40]
Sodium Glucose coTransporter-2 Inhibitors (SGLT2-is)	Empagliflozin Canagliflozin Dapagliflozin	Oral oral oral	↓ Renal threshold for glucose reabsorption increasing glycosuria Modify insulin sensitivity lower insulin requirements ↓ Body weight ↓ Blood pressure ↓ Extracellular volume little changes in High Density Lipoprotein-Cholesterol (HDL-C), triglyceride, and Low Density Lipoproteins-Cholesterol (LDL-C) ↓ Small dense LDL-C	[41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73]