|
| 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 |
|
