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Table 1 Common oral anti-hyperglycaemic therapies and their respective modes of action

From: Understanding glycaemic control and current approaches for screening antidiabetic natural products from evidence-based medicinal plants

Class Example structure Primary mode of action Non-hypoglycaemic benefits Side effects Contraindications References
Sulfonylureas, e.g. tolbutamide, glipizide, glyburide, glimepiride Tolbutamide Increase pancreatic insulin secretion Hypoglycaemia Weight gain Increased risk of CVD Renal and hepatic disease Predisposition to hypoglycaemia T1DM/pancreatic diabetes Pregnancy Major surgery Sulfa drug allergy [3]
Meglitinides, e.g. repaglinide, nateglinide Repaglinide Increase pancreatic insulin secretion As per sulfonylureas As per sulfonylureas [3]
Biguanides, e.g. metformin Metformin Increase insulin sensitivity Reduce hepatic glucose output Does not cause weight gain Monotherapy does not cause hypoglycaemia Improves lipid profile and other vascular risk factors Anti-atherogenic Gastrointestinal issues Metallic taste Possible impairment of vitamin B12 and B9 absorption Lactic acidosis Risk of hypoglycaemia in combination therapy Renal and hepatic disease Cardiac or respiratory insufficiency History of lactic acidosis Severe infection Pregnancy Alcohol abuse [3, 39, 40]
Thiazolidinediones (glitazones) e.g. pioglitazone, rosiglitazone Rosiglitazone Increase insulin sensitivity Decrease blood pressure Anti-inflammatory activity Beneficial vascular effects Hepatotoxicity Weight gain Fluid retention Congestive heart failure Bone fractures T1DM Hepatic disease Class III or IV heart failure Pregnancy [3, 39, 40]
α-Glucosidase inhibitors, e.g. acarbose Acarbose Reduce absorption of dietary carbohydrates Low risk of hypoglycaemia Does not cause weight gain Protects again microvascular complications Potential to delay development of DM in pre-diabetics Gastrointestinal disturbances: Flatulence Diarrhoea Renal and hepatic disease Irritable bowel syndrome Pregnancy Lactation Children < 12 years [41]
Incretin mimetics/GLP-1R agonists, e.g. exenatide, liraglutide Exenatide Delay gastric emptying Low risk of hypoglycaemia Reduce appetite Nausea Vomiting Diarrhoea Severe renal impairment T1DM Pregnancy Lactation [42, 44]
Incretin-enhancing DPP-4 inhibitors, e.g. sitagliptin, vildagliptin Sitagliptin Delay gastric emptying Low risk of hypoglycaemia Increased risk of infection Headache History of hypersensitivity to sitagliptin [42, 44]
SGLT-2 inhibitors, e.g. dapagliflozin, empagliflozin, ertugliflozin Dapagliflozin Reduce glucose reabsorption in the kidneys Low risk of hypoglycaemia Reduces body weight Blood pressure reduction Increased risk of urinary tract infections Risk of ketoacidosis Renal disease  [49,50,51]
SGLT-1/2 co-inhibitors Reduce glucose reabsorption in the kidneys Delay intestinal glucose absorption Low risk of hypoglycaemia Reduces body weight Blood pressure reduction Increased risk of urinary tract infections Risk of ketoacidosis Diarrhoea Renal disease  [52, 53]