Rosiglitazone is an anti-diabetic drug marketed by GlaxoSmithKline (GSK) under the brand name Avandia which works as an insulin sensitizer. It binds to the PAR receptors in fat cells and makes the cells more responsive to insulin. It is marketed as a stand-alone drug or for use combined with glimepiride or with metformin.
This anti-diabetic drug is effective in increasing blood sugar in type two diabetes mellitus. However, studies revealed that the drug may be linked with higher risks of heart attacks and even death. As of July 2010, GSK has faced more than 13,000 lawsuits due to alleged adverse effects of the drug, 5000 of which the British drug company settled to.
In a new study published online in the journal Endocrinology, researchers from the School of Medicine at the University of North Carolina (UNC) revealed how rosiglitazone substantially increases bone fat, putting a patient at a higher risk of having bone fractures.
"These drugs aren't first or second-line choices of treatment for type-2 diabetes, but some patients do take them," said Maya Styner, MD, a UNC assistant professor of medicine and the study's first author. She also added that some drugs are being developed similar to rosiglitazone, targeting the same cellular pathways.
"We think doctors and patients need to better understand the relationship between diabetes, certain drugs and the often dramatic effect on bone health."
Bone fat is affected when rosiglitazone enhances the peroxisome proliferator-activated receptor (PPAR) which is a critical transcription factor regulating gene expression in cell nuclei. As a diabetes treatment, the drug lowers blood sugar by taking glucose out of the bloodstream. As a high risk factor of bone fracture, however, it turns the glucose into droplets of lipid or fat. While previous studies have shown how some of those lipid droplets get stored inside tissue like belly fat, this new research by Styner's team discovered that fat is also brought inside the bone by rosiglitazone.
According to Styner, they were surprised by the massive amount of bone fat that resulted from patients' use of rosiglitazone. She added that through exercise, the amount of fat was seen to decrease by 10 percent, as in the decrease they saw in mice not given rosiglitazone but fed with a diet high in fat.
Rosiglitazone was first released in 1999 boosting annual sales to about $2.5 billion in 2006. Sales however dove back down to a mere $9.5 million in 2012, after the drug was reported to be linked to an increased risk of heart attack.