New research suggests that several commonly prescribed drugs for Type 2 diabetes may not be as effective at preventing death and cardiovascular diseases, such as heart attacks and stroke, as the oral anti-diabetic drug, metformin.…
Insulin secretagogues (ISs), such as glimepiride, glibenclamide (known as glyburide in the USA and Canada), gliclazide and tolbutamide, have been used to treat Type 2 diabetes since the 1950-1970s. Nevertheless, the long-term risk associated with these drugs has largely been unknown. Metformin is the first drug of choice in Type 2 diabetes, but, until now, there have not been studies investigating the long-term risk of individual ISs compared with metformin.
A study in the European Heart Journal followed a large, unselected group of everyone living in Denmark, aged over 20, who had been treated with either an IS or metformin (monotherapy) between 1997 and 2006, a total of 107,806 people. It found that, compared to metformin treatment, monotherapy with most ISs, including glimepiride, glibenclamide, glipizide and tolbutamide, was associated with a greater risk of death from any cause, and a greater risk of heart attacks, stroke or death from cardiovascular diseases. This was the case both for patients who had already suffered a heart attack and for patients who had not. Two other ISs, gliclazide and repaglinide, showed no significant difference to metformin in their effectiveness in patients with and without a history of heart attacks.
Compared to metformin, patients who had not suffered a heart attack had approximately a fifth to a third higher risk of death from any cause if they were taking glimepiride, glibenclamide, glipizide or tolbutamide. In patients with a history of heart attacks, the risk was approximately a third to a half higher.
The researchers, led by Dr Tina Ken Schramm, a senior resident doctor at the Heart Centre at the Rigshospitalet Copenhagen University Hospital (Copenhagen, Denmark), stress that the findings may not mean that these ISs actually cause harm, but only that they appear to be less effective than metformin.
“Previous studies have shown that ISs, in particular sulphonylureas, are associated with a reduction in long-term risk. Therefore, the increased risk from ISs shown in our study presumably has more to do with the beneficial effects of metformin, gliclazide and repaglinide, than the detrimental effect of the other ISs,” explained Dr Schramm. “This is the first study to compare all ISs with metformin despite a wide debate on the possible cardiovascular risk associated with ISs for about three decades. Our findings emphasise how important it is to conduct long-term follow up studies of glucose-lowering medications.”
Online in the European Heart Journal April 6, 2011