|
Class | Main physiological actions | Advantages | Disadvantages |
|
Biguanides (metformin) | hepatic glucose production insulin sensitivity | Weight neutral CVD events (UKPDS [18]) No hypoglycaemia Low cost | Gastrointestinal side-effects (diarrhoea, bloating) Vitamin B12 deficiency Lactic acidosis Contraindicated in CKD, hypoxia, infections, contrast media |
|
Sulphonylureas (glibenclamide, glipizide, gliclazide, glimepiride) | insulin secretion | Microvascular benefits (UKPDS [18]) Low cost | Hypoglycaemia Weight gain Accumulation in renal impairment decrease ischaemic preconditioning QT abnormalities |
|
Thiazolidinediones (pioglitazone, rosiglitazone) | insulin sensitivity | No hypoglycaemia Sustained control triglycerides (pioglitazones) HDL-C | Oedema/heart failure Fragility fractures weight LCL-C (rosiglitazone) MI (meta-analysis, rosiglitazone) |
|
-glucosidase inhibitors (acarbose) | carbohydrate absorption | No hypoglycaemia postprandial hyperglycaemia CVD events (STOP-NIDDM [19]) Not absorbed systemic | Gastrointestinal side-effects Modest glycaemic benefit Frequent dosing with meals |
|
DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin) | ↑ insulin secretion ↓ glucagon secretion | No hypoglycaemia Weight neutral Dose-adjusted in renal impairment (Linagliptin, metabolised in liver) Safe in cardiovascular disease (sitagliptin- TECOS [20], alogliptin- EXAMINE [21]) | Angioedema/urticaria Arthralgia ? pancreatitis ? heart failure (saxagliptin, SAVOR-TIMI 53 [22]) |
|
GLP-1 agonists (exenatide, exenatide extended release, liraglutide, albiglutide, lixisenatide, dulaglutide, semaglutide) | ↑ insulin secretion ↓ glucagon secretion ↑ satiety ↑ gastric emptying | No hypoglycaemia ↓ weight CVD benefits (LEADER [23], SUSTAIN 6 [24]) ↓ postprandial hyperglycaemia (short-acting GLP-1 agonist) ↓ fasting glucose (long acting GLP-1 agonist) | Injectable Education about administration ↑ heart rate Gastrointestinal side-effects ? pancreatitis risk C-cell hyperplasia/medullary thyroid cancer in animals |
|
SGLT-2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) | ↓ renal glucose reabsorption | No hypoglycaemia Diuresis ↓ blood pressure ↓ weight ↓ CVD events (EMPA REG [25]) | Genitourinary tracts infections Dehydration (dose adjustment of diuretics) Euglycaemic diabetic ketoacidosis ↑ LDL-C ? fragility fractures (canagliflozin) |
|
Insulin | ↓ hepatic glucose production ↑ glucose uptake | Theoretically no ceiling effect ↓ microvascular risk | Injectable Education about administration Hypoglycaemia Weight gain |
|