The diabetes drug Avandia, also known as rosiglitazone, has been suspended by UK and European drug watchdogs. The drug, which is used to control blood sugar in type 2 diabetes, has been linked to an increased risk of heart attack and stroke.
In light of these risks, both the European Medicines Agency (EMA) and the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) have recommended that the drug is no longer prescribed. This prescribing ban also applies to Avandamet and Avaglim, two related drugs also containing rosiglitazone.
Up until now diabetes drugs containing rosiglitazone have been considered when diabetes cannot be controlled using either of the first-choice medications, metformin and sulphonylurea. The heart risk has been recognised for some time, with previous rulings by the MHRA saying that the drugs should not be used in people with heart failure or cardiovascular disease. However, continuing research into the safety of the drug has now led an advisory committee of the EMA to call for rosiglitazone to be withdrawn altogether. It echoes similar moves by the US Food and Drug Administration (FDA), which has recently placed tight restrictions on rosiglitazone drugs.
What is rosiglitazone, or Avandia?
Rosiglitazone is a drug designed to help control type 2 diabetes by reducing the body’s resistance to insulin, ie allowing insulin to do its normal job of reducing blood glucose levels.
It is not a first-choice (first-line) diabetes medication, but until now it has been used to treat some patients who do not have adequate blood sugar control when taking the first-choice medications – metformin, a sulphonylurea drug or a drug combining both. In these cases rosiglitazone may be prescribed, either on its own or in combination with metformin or a sulphonylurea drug.
Rosiglitazone has also been prescribed for people already taking the combination of metformin and a sulphonylurea drug, but who need extra blood sugar control and cannot take insulin.
Rosiglitazone is supplied under the brand name Avandia, manufactured by GlaxoSmithKline. Rosiglitazone is also found in a drug called Avandamet, which combines rosiglitazone with metformin. Avandamet is subject to the same suspension as Avandia. Rosiglitazone is also found in the drug Avaglim, though this drug is not licensed for use in the UK.
Rosiglitazone was introduced in July 2000. There are currently an estimated 55,300 people taking Avandia in the UK, plus around 34,500 taking Avandamet.
What is the basis for these current reports?
In July 2010 the Commission on Human Medicines (CHM) in Europe, an independent committee responsible for providing expert advice on drug safety, conducted a review into the safety of rosiglitazone after studies had demonstrated an increased risk of cardiovascular disease with the drug.
The Chair of the CHM subsequently informed the MHRA (the UK government agency responsible for ensuring that medicines and medical devices are safe and effective) that “the benefits of rosiglitazone are no longer considered to outweigh the risks”.
Importantly, the CHM’s review was not able identify any groups, including people without a raised risk of cardiovascular disease, for whom the benefits of rosiglitazone could outweigh the risks. The MHRA has issued advice to both healthcare professionals and patients who are currently using Avandia, Avandamet or Avaglim.
The EMA has recommended that all medications containing rosiglitazone should be completely withdrawn from the market in the next few months. The most recent press release from the FDA says that it will “significantly restrict access” to Avandia. The FDA has also restricted clinical trials involving the drug.
What does the MHRA advise doctors?
The European review into the safety of rosiglitazone considered all available data, including several recent studies involving the drug. These studies were well-conducted and involved a large number of people with diabetes, and should therefore be seen as contributing to the growing body of global evidence.
The combined evidence suggests that rosiglitazone increases cardiovascular risk when compared with both inactive placebo and with pioglitazone, another anti-diabetes drug within the same class as rosiglitazone. Pioglitazone is marketed under the brand name Actos, or as Competact when combined with metformin.
In light of this review and the restrictions already placed on the use of rosiglitazone, (ie that it should not be used in people with heart failure or cardiovascular disease) the MHRA recommends that doctors should:
- Put a system in place that ensures that all patients currently prescribed rosiglitazone are reviewed and changed to another suitable medication.
- Invite patients to visit in the near future rather than wait for the next routine appointment. It is hoped this will to reduce any patient anxiety.
Diabetes is already a known risk factor for cardiovascular disease. If a person has suffered heart disease or a stroke while taking rosiglitazone, it is unfortunately not possible to say what role, if any, their medication could have played.
What does this mean for patients?
The MHRA’s advice to patients is that:
- Those who are prescribed Avandia, Avandamet or Avaglim should not stop taking their treatment. This is because the drugs will still be needed to manage blood sugar levels and there may be some risk in going unmedicated. Instead patients should contact the doctor or nurse supervising their diabetic treatment, who will issue appropriate guidance and an alternative drug for controlling blood sugar.
- Any fluid retention in the ankles or body that occurs as a result of rosiglitazone is likely to be reversed on stopping the medicine. However, as it is not known for certain by what mechanism rosiglitazone may increase the risk of heart disease, it cannot be said that the risk of heart disease decreases completely when people stop taking rosiglitazone.
- Patients should be routinely monitored for cardiovascular disease. However, if they have been experiencing shortness of breath, chest pains/tightness, fatigue, increase in weight, or swelling of ankles (or elsewhere), they should arrange to see their doctor or nurse as soon as possible.
- This guidance refers only to drugs containing rosiglitazone, ie Avandia, Avandamet and Avaglim. It does not apply to other diabetes medications.
Patients can discuss any concerns they have about their treatment with the doctor or nurse looking after their diabetes