Rosiglitazone, sold under the name Avandia (r), is part of a class of oral antidiabetic appeared on the market in 2002: thiazolidinediones.
Mode of action
The mode of action differs from other antidiabetic agents. Rosiglitazone acts on the receptor PPAR gamma, which induces an increased sensitivity of cells to insulin, and therefore a better use of it. The rosiglitizone acts on adipocytes (fat cells), hepatocytes (liver cells) and muscle cells.
Thus HbA1c, the primary indicator of the seriousness of diabetes can be reduced significantly. During clinical trials, rosiglitazone increased HDL-cholesterol and LDL-cholesterol. The High Health Authority (HAS) French has found no data on the ability of this molecule to prevent or stabilize diabetic microangiopathy.
Rosiglitazone would significantly reduce the risk of pre-diabetic subject to develop into true diabetes.
Side Effects and Precautions
Rosiglitazone does not cause hypoglycemia except in combination with sulfonylureas. It can not be prescribed to patients with heart failure irrespective of the degree (class I to IV of NYHA, due to sodium and water retention and increased pulmonary capillary permeability) or hepatic insufficiency or in cases of pregnancy. It is often associated with other oral antidiabetics.
In May 2007, the New England Journal of Medicine published a meta-analysis of 42 studies showed that the risk of heart attack was 43 percent higher among patients taking Avandia than for others. At that time, Glaxo issued a statement approved by the Federal Ministry of Health, which stated that patients taking Avandia should not stop doing so without first consulting their doctor!
However, it increases the risk of myocardial infarction, increasing the risk of cardiovascular death Contrary to a previous assessment. Researchers at the Institute for Clinical Evaluative Sciences in Toronto conducted a study from the database of health insurance for Ontario, including 159.026 diabetics aged 66 years, followed for an average of 3 8 years, until March 2006, assessing the risk of myocardial infarction, congestive heart failure and death. Patients treated with thiazolidinediones may have increased by 60% of congestive heart failure, 40% of myocardial infarction, 29% died, compared with patients treated with other antidiabetic. "The risks of thiazolidinediones outweigh the benefits, even in patients who had no cardiovascular disease initially obvious," say the researchers. The risk of death is increased by thiazolidinediones not only alone but also in combination therapy (with other antidiabetic). This emphasizes the relationship of cause and effect with this class of drugs and contrast with the decreased morbidity and mortality caused by other diabetes drugs. In addition, even a past use of TZDs increases the risk of death. Diabetics treated with TZDs had increased mortality from all causes, that is to say, not only by myocardial infarction or congestive heart failure. Finally, the mortality of diabetes in this cohort was independent of the cardiovascular state before the start of treatment or duration of diabetes. This means that diabetics who had no cardiovascular symptoms and / or who had diabetes recently, a priori, without complications, could equally suffer such adverse effects of TZDs or die. The results of the study is therefore built into false against what was said so far, that TZDs would be handled only with caution in people at high risk of congestive heart failure. No sub-group has been protected from the adverse effects of Avandia and Actos. Abstract original study and reference: Thiazolidinediones and Cardiovascular Outcomes in Older Patients With Diabetes, Lipscombe et al, JAMA, 298, 12 December 2007, p 2634-2643.
These facts call into question, for some, the interest of this molecule, until further studies. This increased risk does not seem proper to the class of thiazolidinediones, as other molecules of the latter seem, however, the protective cardiovascular benefit.
This risk is important enough that several learned societies in 2008 were issued negative opinions about the continued use of this molecule.
Read also Diabetes mellitus