Table 1: Mode of action, advantages, and disadvantages of hypoglycaemic drugs.

ClassMain physiological actionsAdvantagesDisadvantages

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 secretionMicrovascular benefits (UKPDS [18])
Low cost
Hypoglycaemia
Weight gain
Accumulation in renal impairment
decrease ischaemic preconditioning
QT abnormalities

Thiazolidinediones
(pioglitazone, rosiglitazone)
insulin sensitivityNo hypoglycaemia
Sustained control
triglycerides (pioglitazones)
HDL-C
Oedema/heart failure
Fragility fractures
weight
LCL-C (rosiglitazone)
MI (meta-analysis, rosiglitazone)

-glucosidase inhibitors
(acarbose)
carbohydrate absorptionNo 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 reabsorptionNo 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

CKD: chronic kidney disease, CVD: cardiovascular disease, and MI: myocardial infarction.