MRCGP exam update: Use of glitazones

Current situation 

  • Many patients with type-2 diabetes will need more than one drug to control their blood glucose levels.
  • Glitazones work by reducing the body's resistance to the action of insulin and enable a more efficient use of insulin. 

What is the evidence?

  • The PROactive study found that the use of pioglitazone reduced the primary endpoint of death, MI or stroke by 15 per cent (Lancet 2005; 366: 1279). The trial, including 5,238 patients with type-2 diabetes and evidence of macrovascular disease, also found pioglitazone reduced HbA1c levels by 0.8 per cent. However, there was an increased incidence of heart failure in patients taking pioglitazone. In addition, some critics have commented that the cardiovascular benefits of pioglitazone over placebo were unlikely to have been demonstrated had all patients received statins. At the start of the study, 43 per cent of the patients were on statins.
  • One article challenged the interpretation of PROactive, stating that the study's interpretation is based on secondary outcomes  because the primary outcome remained neutral. The article explains why the conclusions presented may be statistically unsound and unsafe (BMJ 2005; 331: 836).    
  • Pioglitazone compared with rosiglitazone has been shown to be associated with significant improvements in triglycerides, HDL and LDL cholesterol levels in patients with type-2 diabetes (Diabetes Care 2005; 28: 1547).
  • However, a retrospective study showed that rosiglitazone and pioglitazone, as part of triple oral therapy, are equally effective in reducing HbA1c to recommended levels in patients with type-2 diabetes (Diabetes Care 2006; 29: 1395).

Implications for practice

  • Rosiglitazone may have a role in the prevention of type-2 diabetes in high risk patients, according to another study. Taking rosiglitazone actually reduced the risk of developing type-2 diabetes by an impressive and significant 62 per cent (Lancet 2006; 368: 1096).
  • A study has shown that adding rosiglitazone to a sulphonylurea and metformin is less effective than adding insulin. Patients receiving insulin had lower cholesterol and triglyceride levels and also lower HbA1c levels compared with those given rosiglitazone (Diabetes Care 2006;29:554).
  • Although weight gain can occur in those patients with diabetes taking glitazones, this may not actually be a detrimental side effect, according to one review. There is some evidence that the increase in body weight associated with these drugs may lead to a reduction in central obesity (Intl J Clin Pract 2006; 60: 1272).

Available guidelines

  • NICE recommend that glitazones be used as a second line treatment in combination with either metformin or a sulphonylurea in patients with type-2 diabetes who cannot tolerate metformin and sulphonylurea in combination, and in patients for whom these drugs are contraindicated.

Useful websites - NICE

Dr Louise Newson is a GP in the West Midlands and author of ‘Hot Topics for MRCGP', PasTest, 2006

Key points

  • Glitazones target insulin resistance.
  • Pioglitazone improves HDL-cholesterol levels
  • Rosiglitazone may prevent onset of type-2 diabetes.

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