2021A13 List the major classes of oral hypoglycaemic drugs and provide an example of each class. Briefly outline their mechanisms of action and major side effects.

Class and example

Mechanism of action

Side effects

Biguanide

e.g. metformin

· ↓Hepatic glucose production (by glycogenolysis, gluconeogenesis)

· ↑Insulin sensitivity

· Diarrhoea

· Renal impairment: ↑risk if dehydrated, iodine contrast, other nephrotoxins.

· Rare lactic acidosis (inhibit complex 1 of electron transport chain)

Sulfonylurea

e.g. gliclazide

· Inhibit K⁺-ATP channel -> depolarisation -> activate VDCC -> ↑ICF Ca²⁺ -> exocytosis of insulin vesicles ↑insulin release

· Requires functioning pancreas

· Risk hypoglycaemia peri-op

· Long-term “burnout”, β-cell failure, insulin dependence

Apical SGLT2 inhibitor

e.g. dapagliflozin

· ↓Glucose reabsorption -> glycosuria

· Limit plasma glucose to 10mM

· Weight loss

· UTI

· Osmotic diuresis

· Occult DKA-like state

a-glucosidase inhibitor

e.g. acarbose

· ↓Glucose reabsorption

· Weight loss

· Osmotic diarrhoea, abdominal pain

DPP4 inhibitor

e.g. sitagliptin

· ↓Breakdown of incretins GLP-1 and GIP

· Requires functioning pancreas

· Minimal

· Nausea

· Cold-like symptoms

· Photosensitivity

Thiazolidenedione PPARγ agonists

e.g. rosiglitazone

· ↓Insulin resistance

· Weight gain, oedema, hepatitis