Diabetes treatments increase risk of heart problems in older patients, study finds
Older diabetes patients treated with Takeda Pharmaceutical North American Inc.’s Actos and GlaxoSmithKline Plc.’s Avandia had a “significant” increased risk of heart attack, congestive heart failure and death compared to those taking an older treatment for people with diabetes, according to a study in this week’s Journal of the American Medical Association.
The study, published in the Dec. 12 issue of JAMA, is the latest to call into question the use of diabetes pills known as thiazolidinediones, or TZDs. Avandia and Actos, which generated more than $2 billion in annual sales last year for Deerfield-based Takeda. The only two drugs in the TZD class, Actos and Avandia work by increasing the body’s sensitivity to insulin.
Compared to patients taking oral hypoglycemic drugs, people with diabetes who were over the age of 65 taking TZDs had a 60 percent increased risk of heart failure; a 40 percent increased risk to suffer a heart attack; and had a 29 percent risk of death. The findings are similar to those in a May 21 New England Journal report by researchers at the Cleveland Clinic, which found Avandia increased heart attack risks by 43 percent.
But the Institute for Clinical Evaluative Services in Toronto that led the study for JAMA said in a statement that the risks were “predominantly among those taking” Avandia. Researchers reasoned the limited risks found with Actos were due to fewer numbers of people in the study population received Takeda’s drug.
The researchers say the study is different that highly-publicized earlier studies of the drugs because it was “post-marketing” surveillance rather research trials often criticized as “insufficient to detect less common adverse effects of drugs,” said Dr. Lorraine L. Lipscombe, a researcher at the Institute. “Ongoing safety monitoring of drug side effects in larger real-world populations is vital.”
Avandia and Actos already have the U.S. Food and Drug Administration’s strict so-called “black box” warning about heart failure, which can affect proper blood flow.
Both Glaxo and Takeda took issue with the study in statements Tuesday afternoon. Glaxo said the findings “are not consistent with other epidemiological studies and long-term clinical trials, which do not show a difference in cardiovascular risk between Avandia and other anti-diabetic medicines,” the British drug giant said in a statement. “The inconsistency could be due to the fact that the Avandia patients were older, sicker, and had more chronic diseases.”
Takeda medical director Dr. Bob Spanheimer, medical director for Takeda Pharmaceuticals North America Inc. said there “is no increase in heart attacks or deaths with Actos.”
In the wake of scrutiny by FDA advisers this summer of Avandia at a high-profile advisory panel, Glaxo’s market share has plummet to less than 5 percent of new prescriptions written by primary care doctors for non-insulin prescriptions, according to New Jersey-based ImpactRx, Inc. The FDA panel in July advised a black box warning about heart attack risk for Avandia, which last year generated more than $3 billion in annual worldwide sales.
FDA advisers at that panel acknowledged that Actos has not been as aggressively studied as Avandia. Since that panel, Actos’ market share has fluctuated between 15 and 20 percent, ImpactRx figures show, and benefited from the FDA advisors’ scrutiny of Avandia.
“After some share gains in the immediate aftermath to the Avandia issue, Actos is now essentially back to where it was one year ago,” said Patrick Angelastro Senior Vice President of Strategic Development at ImpactRx.
