Some results of post-hoc meta-analysis are shown:
- LDL cholesterol - treatment with combination treatment with rosiglitazone/metformin for 6 months led to higher LDL cholesterol levels when compared with treatment with metformin alone (the weighted mean difference was 0.31 mmol/l (95% CI 0.16-0.45)). Also treatment with combination treatment with rosiglitazone/sulphonylurea led to higher LDL cholesterol than with treatment with sulphonylurea alone (weighted mean difference 0.2 mmol/l (95% CI 0.07-0.34))
- HDL cholesterol was higher with combination treatment with rosiglitazone/metformin for 6 months than with metformin alone (weighted mean difference 0.13 mmol/l (95% CI 0.08-0.18))
- diastolic blood pressure - patients who had treatment with metformin/rosiglitazone for 6 months in comparison with metformin alone had a marginally lower diastolic blood pressure (weighted mean difference 1.8 mmHg (95% CI 0.3-0.33 mmHg)
- body weight - treatment with rosiglitazone/sulphonylurea had a higher body weight after six months than treatment with sulphonylurea alone (weighted mean difference 3.3kg (95% CI 0.8-5.7kg)
It is difficult to predict the combination of these effects and improved glycaemic control on overall cardiovascular risk (1).
A meta-analysis by Nissen and Wolski (MA) suggests that rosiglitazone may actually increase the risk of MIs (2)
- the MA included 42 randomised controlled trials (RCTs) of at least 24 weeks duration (n=27,843)
- odds ratios [ORs] for rosiglitazone compared with placebo were 1.43 (95%CI 1.03 to 1.98, P=0.03) for MI and 1.64 (95%CI 0.98 to 2.74, P=0.06) for death from cardiovascular (CV) causes
- results are consistent with a similar analysis of 42 controlled double-blind studies (n=14,237) carried out by GlaxoSmithKline (MI: hazard ratio [HR] 1.31; 95%CI 1.01 to 1.70)
"...Although effects on glycaemic control of glitazones, metformin and sulphonylureas are similar, glitazones are associated with adverse effects on LDL cholesterol, weight gain, and congestive heart failure....the potential for rosiglitazone to increase the risk of heart failure and MI in patients receiving rosiglitazone has previously been recognised by the MHRA, and is reflected in product information..."(3)
- NICE (August 2000). Guidance on rosiglitazone for type 2 Diabetes Mellitus.
- Nissen SE, Wolski K. N Engl J Med 2007;356:2457–71.
- MeReC Extra (August 2007).Issue 29.