A study published in JAMA reports that the drug pioglitazone is more effective at reducing the rate of plaque build-up in the coronary arteries than the drug glimepiride. Both medications are designed to treat type 2 diabetes (also known as adult-onset diabetes).
For patients with diabetes, atherosclerosis – the process in which plaque sticks to the inner lining of the arteries – can be quite aggressive and result in higher rates of cardiovascular events. Three-quarters of diabetes patients die due to cardiovascular disease, and thus there are important public health implications in determining the best treatment for coronary artery disease for diabetic patients.
Patients with diabetes are prescribed a type of glucose-lowering medication, but currently there is a paucity of evidence that suggests one medication is better than any other at reducing the severity of atherosclerotic disease. One of the most commonly-used classes of antidiabetic therapy medications is called Sulfonylureas, which includes glimepiride. Drugs in this class have been available for decades. A second class of medications, called Thiazolidinediones (TZDs), is relatively new and includes drugs such as pioglitazone.
To compare how the two classes of antidiabetic therapy medication affect the progression of atherosclerotic disease, Steven E. Nissen, M.D. (Cleveland Clinic) and colleagues conducted the PERISCOPE trial. The trial directly compares the effectiveness of the competing hyperglycemia treatments – an insulin-providing strategy (glimepiride) vs. an insulin-sensitizing strategy (pioglitazone). The sample consisted of 543 patients with type 2 diabetes and coronary disease from 97 academic and community hospitals in North and South America. Enrollment in the study took place between August 2003 and March 2006.
To measure the progression of atherosclerosis, all patients underwent coronary intravascular ultrasonography and were randomly assigned to receive either glimepiride or pioglitazone for 18 months. The change in percent atheroma volume (PAV – how much plaque is building up in an artery) measured atherosclerosis progression, and 360 patients received repeat intravascular ultrasonography examinations at the end of the study.
For the group who received glimepiride, there was a 0.73 percentage point increase in the change in PAV. Patients who received pioglitazone averaged a 0.16 percentage point decrease in PAV. A second analysis included imputed values (based on baseline characteristics) for patients without follow-up ultrasound procedures. This resulted in a 0.64 percentage point increase in PAV for the glimepiride group and a 0.06 percentage point decrease in PAV for the pioglitazone group. The researchers also found that the maximum atheroma thickness increased in the glimepiride group and decreased in the pioglitazone group, again pointing to the advantage of pioglitazone.
Nissen and colleagues write, “The observation of a significant benefit for pioglitazone treatment represents, to our knowledge, the first demonstration of the ability of any hypoglycemic agent to slow the progression of coronary atherosclerosis in patients with diabetes. Evidence for a slowing of disease progression has proven a very challenging end point in recent years with the prominent failure of several promising approaches.
The researchers conclude: “Patients randomized to pioglitazone exhibited a lower rate of progression of coronary atherosclerosis across a wide array of prespecified and exploratory subgroups. These finding may have important implications for defining the optimal strategy for management of patients with type 2 diabetes and coronary atherosclerosis.
An editorial written by Philippe Gabriel Steg, M.D. (Centre Hospitalier Bichat-Claude Bernard, Paris, and Editor, JAMA-français), and Michel Marre, M.D. (Université Paris VII Faculté de Médecine X Bichat, Paris), includes the following comment regarding the research of Dr. Nissen and colleagues:
“The results of the PERISCOPE trial, even though they relate to a surrogate end point, are consistent with the modest clinical benefit demonstrated for the prevention of coronary events with pioglitazone, within PROACTIVE and other trials. However all glitazones share a common adverse effect on heart failure, and other noncardiovascular adverse effects, such as bone fractures. . Overall, in the current context of concerns regarding the cardiovascular safety of glucose lowering and regardless of the mechanisms involved, PERISCOPE provides a reassuring perspective for patients with type 2 diabetes and high cardiovascular risk.”
Comparison of Pioglitazone vs Glimepiride on Progression of Coronary Atherosclerosis in Patients With Type 2 Diabetes: The PERISCOPE Randomized Controlled Trial
Steven E. Nissen; Stephen J. Nicholls; Kathy Wolski; Richard Nesto; Stuart Kupfer; Alfonso Perez; Horacio Jure; Robert De Larochellière; Cezar S. Staniloae; Kreton Mavromatis; Jacqueline Saw; Bo Hu; A. Michael Lincoff; E. Murat Tuzcu
JAMA (2008). 299[13]:1561-1573
Written by: Peter M Crosta