2013C01 What are the major classes of oral hypoglycaemic agents? Outline their mechanisms of action and possible 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

 

 

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