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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]