Which Diabetes Medication Is Better At Slowing Down Atherosclerosis?
April 1st, 2008 | by admin |A study published in JAMA reports that the drugpioglitazone is more effective at reducing the rate of plaque build-upin the coronary arteries than the drug glimepiride. Both medicationsare designed to treat type 2 diabetes (also known as adult-onsetdiabetes).
For patients with diabetes, atherosclerosis - the process in whichplaque sticks to the inner lining of the arteries - can be quiteaggressive 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 determiningthe best treatment for coronary artery disease for diabetic patients.
Patients with diabetes are prescribed a type of glucose-loweringmedication, but currently there is a paucity of evidence that suggestsone medication is better than any other at reducing the severity ofatherosclerotic disease. One of the most commonly-used classes ofantidiabetic therapy medications is called Sulfonylureas, whichincludes glimepiride. Drugs in this class have been available fordecades. 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 medicationaffect the progression of atherosclerotic disease, Steven E.Nissen, M.D. (Cleveland Clinic) and colleagues conducted the PERISCOPEtrial. The trial directly compares the effectiveness of thecompeting hyperglycemia treatments - an insulin-providing strategy(glimepiride) vs. an insulin-sensitizing strategy (pioglitazone). Thesample consisted of 543 patients with type 2 diabetes and coronarydisease from 97 academic and community hospitals in North and SouthAmerica. Enrollment in the study took place between August 2003 andMarch 2007.
To measure the progression of atherosclerosis, all patients underwentcoronary intravascular ultrasonography and were randomly assigned toreceive either glimepiride or pioglitazone for 18 months. The change inpercent atheroma volume (PAV - how much plaque is building up in anartery) measured atherosclerosis progression, and 360 patients receivedrepeat intravascular ultrasonography examinations at the end of thestudy.
For the group who received glimepiride, there was a 0.73 percentagepoint increase in the change in PAV. Patients who received pioglitazoneaveraged a 0.16 percentage point decrease in PAV. A second analysisincluded imputed values (based on baseline characteristics) forpatients without follow-up ultrasound procedures. Thisresulted in a 0.64 percentage point increase in PAV for the glimepiridegroup and a 0.06 percentage point decrease in PAV for the pioglitazonegroup. The researchers also found that the maximum atheroma thicknessincreased in the glimepiride group and decreased in the pioglitazonegroup, again pointing to the advantage of pioglitazone.
Nissen and colleagues write, “The observation of a significant benefitfor pioglitazone treatment represents, to our knowledge, the firstdemonstration of the ability of any hypoglycemic agent to slow theprogression of coronary atherosclerosis in patients with diabetes.Evidence for a slowing of disease progression has proven a verychallenging end point in recent years with the prominent failure ofseveral promising approaches.
The researchers conclude: “Patients randomized to pioglitazoneexhibited a lower rate of progression of coronary atherosclerosisacross a wide array of prespecified and exploratory subgroups. Thesefinding may have important implications for defining the optimalstrategy for management of patients with type 2 diabetes and coronaryatherosclerosis.
An editorial written by Philippe Gabriel Steg, M.D. (Centre HospitalierBichat-Claude Bernard, Paris, and Editor, JAMA-fran?ais), and MichelMarre, M.D. (Université Paris VII Faculté de Médecine X Bichat,Paris), includes the following comment regarding the researchof Dr. Nissen and colleagues:
“The results of the PERISCOPE trial, even though they relate to asurrogate end point, are consistent with the modest clinical benefitdemonstrated for the prevention of coronary events with pioglitazone,within PROACTIVE and other trials. However all glitazones share acommon adverse effect on heart failure, and other noncardiovascularadverse effects, such as bone fractures. . Overall, in the currentcontext of concerns regarding the cardiovascular safety of glucoselowering and regardless of the mechanisms involved, PERISCOPE providesa reassuring perspective for patients with type 2 diabetes and highcardiovascular risk.”
Comparison of Pioglitazone vs Glimepiride on Progression ofCoronary Atherosclerosis in Patients With Type 2 Diabetes: ThePERISCOPE 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
ClickHere to View Abstract
Written by: Peter M Crosta
Copyright: Medical News Today
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