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