💊 Thiazolidinediones
Drug Class & Overview
Thiazolidinediones (TZDs), also known as glitazones, are a class of oral antidiabetic drugs used in the management of type 2 diabetes mellitus.
Mechanism of Action
They act as agonists for peroxisome proliferator-activated receptor gamma (PPAR-γ), a nuclear receptor primarily expressed in adipose tissue. Activation of PPAR-γ leads to increased insulin sensitivity in peripheral tissues (muscle, fat) and the liver, reducing insulin resistance and improving glucose uptake.
Key Indications
Primarily used in type 2 diabetes mellitus, often as an add-on therapy, particularly in patients who cannot tolerate or are contraindicated to metformin, or when other oral agents are insufficient. Pioglitazone is the main TZD available in the UK.
Contraindications
Heart failure (any New York Heart Association class) is an absolute contraindication due to fluid retention. Hepatic impairment, bladder cancer (current or history of), and uninvestigated macroscopic haematuria are also contraindications. Pregnancy and breastfeeding are also contraindications.
Adverse Effects
Common adverse effects include fluid retention, leading to oedema and weight gain, and can exacerbate or precipitate heart failure. Other effects include increased risk of bone fractures (especially in women) and anaemia. There is a small increased risk of bladder cancer with pioglitazone.
Monitoring
Liver function tests (LFTs) should be monitored before initiation and periodically thereafter, as TZDs can cause idiosyncratic liver injury. Patients should be monitored for signs and symptoms of heart failure (e.g., dyspnoea, oedema, rapid weight gain). Bone mineral density may be considered in at-risk patients.
Prescribing Safety (OSCE)
Crucially, always check for a history of heart failure or symptoms of fluid overload before prescribing. Counsel patients on the importance of reporting any new or worsening dyspnoea or oedema. Discuss the risk of weight gain and the small increased risk of bladder cancer. Ensure LFTs are checked.
MLA High-Yield Notes
High-yield for their contraindication in heart failure and the mechanism of action (PPAR-γ). Remember the side effects of fluid retention, weight gain, and increased fracture risk. Pioglitazone is the only TZD widely used in the UK. Be aware of the bladder cancer risk and the need for careful patient selection.
Common SBA Themes
SBAs frequently test the contraindication of heart failure, asking which drug should be avoided in such patients. Questions may also focus on the mechanism of action (PPAR-γ agonists) or the side effect of fluid retention/weight gain. Expect scenarios involving patients with a history of heart failure or unexplained oedema.
References
- BNF
- NICE NG28: Type 2 diabetes in adults: management
- MHRA Drug Safety Update