A prominent University of Connecticut Health Center professor is the principal investigator in a clinical trial generating worldwide interest, in which a new diabetes drug was shown to be effective in lowering blood sugar without increasing the risk of dangerous cardiovascular events such as heart attack and stroke.
Certain older diabetes drugs that had been approved by the U.S. Food and Drug Administration were later linked to a higher risk of dying from cardiovascular events. In response, the FDA tightened regulations around its approval of such drugs, explains Dr. William B. White, professor of medicine and chief of the Division of Hypertension and Clinical Pharmacology at the UConn School of Medicine’s Calhoun Cardiology Center.
White served as chair of the steering committee and primary author for this new study, called the EXAMINE trial, which tested a drug called alogliptin in people with type 2 diabetes. “Patients with diabetes are at increased risk for cardiovascular disease, roughly two to three times” that of the general population, he explains. This risk became significantly greater when their diabetes was treated with some of the older drugs on the market.
The EXAMINE trial is especially significant because it enrolled people with diabetes who also had preexisting cardiovascular conditions. “The level of risk for our study patients was very high,” White explains. “Since the drug alogliptin (Nesina™) was tested thoroughly in this population and was found to be safe, you could say it’s also safe for patients with type 2 diabetes who have lower cardiovascular risk.”
An article authored by White and his fellow EXAMINE researchers is published in the Oct. 3 issue of the New England Journal of Medicine and is available online now. The results also were presented at the European Society of Cardiology 2013 Congress in Amsterdam, Netherlands, on Sept. 2, where tens of thousands of medical professionals worldwide listened via a hotline presentation.
Diabetes is a condition in which the body does not properly process carbohydrates in food. The body works to turn food into glucose, or sugar, to be used for energy. An organ near the stomach called the pancreas makes a hormone called insulin to help glucose enter the body’s cells.
There are two types of diabetes. In type 1, the pancreas produces virtually no insulin. In type 2 diabetes, which is much more common, either the body does not make enough insulin or can’t use its own insulin properly, causing sugar to build up in the blood.
Diabetes is a leading cause of death and disability in the U.S. It can cause serious health problems such as heart disease, blindness and kidney failure, and can lead to limb amputations.
Alogliptin, a type of drug called a dipeptidyl peptidase (DPP-4) inhibitor, works by helping the pancreas make insulin and use it more efficiently. It was developed by Takeda Development Center, Inc and is marketed under the brand name Nesina.
The EXAMINE trial recruited 5,380 patients from 898 centers in 49 countries from October 2009 through March 2013. Patients were eligible for enrollment if they had type 2 diabetes, were receiving standard anti-diabetic therapy, and had a recent history of acute coronary syndrome. Patients in the study were randomized, with some receiving alogliptin and others receiving placebo (a pill containing no active medication).
The study was the first cardiovascular safety trial of an anti-diabetic drug in patients with acute coronary syndrome. Because alogliptin demonstrated no increase in cardiovascular risk over the median study duration of 18 months, it is a reassuring new option for blood sugar control for people with type 2 diabetes.
Alogliptin is intended to be used in combination with other types of anti-diabetes medication to keep blood sugar under control. “Our purpose was to prove this drug’s safety and effectiveness in the treatment of diabetes, and we met that endpoint,” White says. “The risk of major cardiovascular events was not higher than placebo.”
The findings from the EXAMINE trial “could guide clinicians to choose among the many anti-diabetic agents available when treating patients with type 2 diabetes and very high cardiovascular risk,” White says. “In the past, we didn’t know about the safety of drugs on the market the way we know about this drug.”