Table 1.

Metabolic effects of antidiabetic drugs; symbols: ⬆—increase, ⬇—decrease.

Metformin	Sulphonylureas	SGLT-2 Inhibitors	DPP-4 Inhibitors	GLP-1 Agonists	Thiazolidinediones	Insulin
↓ intestinal glucose absorption	↑ insulin release by pancreatic B-cells	↑ urinary glucose excretion	↑ endogenous incretin concentration of GLP-1 and GIP	↑ GLP-1 receptor activation	↑ uptake of free fatty acids by adipocytes	↑ glucose utilization and storage by increasing glucose transport and net glycogen synthesis
↑ glucose utilization by intestinal cells	↑ tissue sensitivity to insulin	↑ glucose utilization	↑ sensitivity of pancreatic B-cells to glucose and ↑ glucose dependent insulin secretion	↓ glucagon secretion in a-cells	↑ secretion of adiponectin	↑ glucose transport into cells and net glycogen synthesis
↓ hepatic gluconeogenesis and glycogenolysis	↑ glucose transport into adipose tissue and muscles	↓ insulin resistance	↑ sensitivity of a-cells to glucose, glucagon secretion	↑ glucose-dependent insulin secretion	↓ production of TNF-a	white adipose tissue (WAT): ↓ lipolysis, ↑ glucose transport, ↑ lipogenesis
↑ glucose uptake and utilization by peripheral tissues	↑ glycogenesis in liver and muscles	↓ glucotoxicity	↓ hepatic glucose secretion both in fasting and postprandial states	↓ B-cell death, ↑B-cell proliferation, ↑ expansion of B-cell mass	↓ production of resistin	Liver: ↑ activation of glycogen synthesis, ↑ lipogenic gene expression, ↓ gluconeogenic gene expression
↑ peripheral insulin sensitivity	↓ synthesis of glucose and oxidation of fatty acids in the liver	adipose tissue: ↑ lipolysis, fatty acid oxidation and ketone body formation, ↓ visceral and epicardial fat mass	delay in gastric emptying, ↓ caloric intake and weight loss	↓ islet inflammation	↑ HDL-cholesterol concentration	Muscle cells: ↑ glycogenesis and ↓ protein synthesis, protein catabolism
↑ fatty acid oxidation in adipose tissue and skeletal muscles		Hepatic: ↑ gluconeogenesis, ↑ ketogenesis, ↑ hepatic glucose output, ↓ hepatic steatosis		↑ delayed gastric emptying, ↓ food intake, ↑ weight loss	↑ LDL-cholesterol concentration and particle size	Pancreatic beta cells: ↓ glucagon release
↑ lipolysis and inhibits lipogenesis		Cardiovascular: ↓ intravascular volume, ↓ blood pressure, ↓ cardiac preload and afterload, improves endothelial and ↓ vascular stiffness			↓ triglyceride concentration
↓ the nuclear factor KB pathway in immune cells					↓ plasminogen activator inhibitor-1 and fibrinogen
↓ the differentiation of monocytes to macrophages					anti-inflammatory effects
↓ inflammation