- Type 2 diabetes mellitus, usually added to other agents when further glucose lowering is needed (see NICE guidance)
- Reduces HbA1c by a modest 8-11mmol/mol (0.75-1%)
Thiazolidinediones
Thiazolidinediones
Resources
- Thiazolidinediones ('glitazones') increase insulin sensitivity
- Pioglitazone is the only thiazolidinedione available in the UK
- Troglitazone was withdrawn owing to hepatotoxicity and rosiglitazone owing to cardiovascular risk
- Use has declined given concerns over heart failure and bladder cancer
- Agonists of peroxisome proliferator-activated receptor-γ (PPAR-γ), a nuclear transcription factor
- This alters transcription of multiple genes involved in glucose and lipid metabolism
- Increases insulin sensitivity in liver, adipose tissue and skeletal muscle
- Acts very slowly: effects take weeks to develop and 4-6 months for maximum benefit
- Enhances the action of endogenous insulin, so the risk of hypoglycaemia in the starved state is low
Absorption
- High oral bioavailability
Metabolism
- Extensive hepatic metabolism by CYP450 enzymes; some metabolites are active
- Liver function should be monitored
Excretion
- Excreted in urine and faeces
Cardiovascular
- Fluid retention and oedema, which may precipitate or exacerbate heart failure
Renal and urological
- Possible increased risk of bladder cancer, although this is largely unsubstantiated
Nutritional and metabolic
- Weight gain
- Low risk of hypoglycaemia when used alone
MSK
- Increased risk of limb fractures
Other
- Macular oedema
- Hepatotoxicity (class effect, prominent with troglitazone)
Perioperative management
- Take as normal (UK guidance), as it does not cause hypoglycaemia and its slow onset and offset mean short omission has little effect
- Some international guidance recommends withholding on the day of surgery as a precaution
- Can be continued before bariatric surgery, including during a liver reduction diet
- Be aware of potential fluid retention and occult heart failure
- Target capillary blood glucose 4-10mmol/L if not on insulin or secretagogues
- Continue once eating and drinking
- Review the ongoing need after bariatric surgery
- Use in critical care is a concern, where fluid overload is already common