Diabetes is becoming the most common disease due to america’s obesity. Let’s face it, we all enjoy good meals made from butter, bacon and fried foods. In moderation, this meals are ok for us but the concept of moderation doesn’t seem to be in our vocabulary. I have some bad news, Roche, the Swiss pharmaceutical company, has discontinued development of a potentially important diabetes drug. This move that could raise new safety questions about the entire category of drugs, which includes the controversial diabetes medicine Avandia. The company said that it decided to halt that study and all others involving the drug because of safety signals and lack of efficacy.
What is Aleglitazar?
Aleglitazar was designed to treat not only diabetes but cardiovascular risk factors like cholesterol as well. Aleglitazar was being tested not only for its ability to lower blood sugar, but also to see if it could prevent heart attacks and strokes in people with Type 2 diabetes. Aleglitazar works by activating two receptors in the body, known as PPAR alpha and PPAR gamma. Current diabetes medications control blood sugar by activating one of the two receptors but have not generally been shown to lower the risk of heart attacks and strokes. Roche aimed for a drug that activated both receptors equally, hoping it would improve both blood lipids and blood sugar, and lower the extra cardiovascular risks that diabetics face. This testing failure cost several hundred million dollars and has set back a new way of treating diabetic patients.
What is Avandia?
Avandia (Rosiglitazone) is a thiazolidinedione class of drugs. It works as an insulin sensitizer, by binding to the PPAR receptors in fat cells and making the cells more responsive to insulin. Avandia activates mainly the gamma receptor. One of the major side effects of this drug is heart attacks and strokes. The failure of aleglitazar could conceivably play into the F.D.A.’s deliberations over Avandia, which has a somewhat similar mechanism of action. Avandia’s use was severely restricted in the United States and banned in Europe in 2010 because of concerns it could raise the risk of heart attacks and stroke.
Clinical Trial Failure
The study of aleglitazar involved more than 7,000 people with diabetes in numerous countries, all of whom had also suffered a recent heart attack or the onset or worsening of cardiac pain. The study was supposed to last five years, until around the beginning of 2015. But several other dual PPAR agonists, as the drugs are called, failed because of various safety issues years ago, leaving Roche perhaps the last big company pursuing that type of drug. Previous failures included AstraZeneca’s Galida, which led to kidney problems, Merck’s MK-767, which produced tumors in mice, and Takeda’s TAK-559, which caused liver problems.
Bristol-Myers Squibb’s Pargluva was actually recommended for approval by an F.D.A. advisory committee in 2005. But shortly thereafter other researchers at the Cleveland Clinic published an analysis showing that the drug might increase the risk of heart attacks and strokes. The F.D.A. also requested more safety data, and Bristol-Myers discontinued development.
Where you on any of these medications?