Actos Cut Risk of Prediabetes Becoming Diabetes in Study
WEDNESDAY March 23, 2011 -- Researchers report that taking the diabetes drug Actos helped people who had prediabetes avoid getting type 2 diabetes.
"Pioglitazone [Actos] was extremely effective in preventing diabetes," said study author Dr. Ralph DeFronzo, deputy director of the Texas Diabetes Institute and chief of the diabetes division at the University of Texas Health Science Center in San Antonio. The actual reduction in risk was 72 percent.
"The reason that people go from prediabetes to diabetes is that the insulin-producing beta cells fail. By the time someone is diagnosed with prediabetes, they may have lost 70 percent to 80 percent of beta cell function. Pioglitazone improves how the body responds to insulin and protects the beta cells from failing," he explained.
The study, which was funded by the drug's manufacturer, Takeda Pharmaceuticals, is published in the March 24 issue of the New England Journal of Medicine.
The U.S. Centers for Disease Control and Prevention estimates that as many as 79 million Americans may have prediabetes, with about half of those cases in people older than 65. Changes in lifestyle -- losing 5 percent of body weight and exercising at least 30 minutes a day most days of the week -- often helps prevent prediabetes from turning into type 2 diabetes. However, most people aren't able to maintain those lifestyle changes over the long term, DeFronzo noted.
After diet and exercise, the next recommended therapy is a drug called metformin. "Metformin can reduce the risk of diabetes by about 30 percent," said Dr. Vivian Fonseca, president-elect of medicine and science for the American Diabetes Association.
The current study was designed to assess whether or not Actos was more effective than a placebo in reducing the risk of developing type 2 diabetes.
The study included 602 people over the age of 18 who had been diagnosed with prediabetes. All of the study participants had a body-mass index over 25, which meant that they were either overweight or obese.
Study participants were randomly assigned to receive either 45 milligrams of pioglitazone daily or a placebo. Each participant had fasting blood sugar tests done quarterly, and glucose tolerance testing done annually to check for diabetes. The average follow-up time was 2.4 years.
The average rate that type 2 diabetes developed in the study participants was 2.1 percent for the pioglitazone group and 7.6 percent in the placebo group. And, nearly half of those on pioglitazone returned to normal blood sugar levels, while just 28 percent of those in the placebo group did.
In addition, people in the pioglitazone group averaged lower blood pressure, and had reduced inta-media carotid thickening (a measure of plaque build-up in the carotid artery). Levels of "good" HDL cholesterol also increased in the pioglitazone group.
The news wasn't all good, however. The people in the pioglitazone group experienced more adverse events (151 vs. 121) and gained an average of about nine pounds, and experienced more fluid retention (edema), than people taking the placebo. (The U.S. Food and Drug Administration has warned that, as with other thiazolidinediones, pioglitazone can cause fluid retention, potentially leading to or exacerbating heart failure.)
However, DeFronzo said that the weight gain was somewhat paradoxical because the drug causes fat deposits in superficial tissues, and moves fat out of the liver, heart and abdomen, where it's more detrimental to your health.
Fonseca said the results from this study look excellent, but added, "One has to consider the lack of knowledge of long-term safety in a population that's already at risk of disease."
"People with prediabetes should seriously think about healthy lifestyle changes first, and if you can't achieve a healthy lifestyle, you should talk to your doctor about medical treatments," said Fonseca. He said the American Diabetes Association recommends metformin as the first-line treatment if lifestyle changes don't work. Metformin is much cheaper than Actos because it's available as a generic. In addition, he said, it's been available for decades so its side effect profile is well-known.
Although Fonseca was not involved in this study, he disclosed that he is a paid consultant to Takeda Pharmaceuticals as a member of its new drug data safety monitoring board.
DeFronzo, however, recommended initiating drug treatment and lifestyle changes at the same time in people who are at a high risk of developing type 2 diabetes. People at high risk of type 2 diabetes include people with a family history of diabetes, women who've had gestational diabetes, Hispanics, blacks or Native Americans, people with metabolic syndrome, people who are overweight or obese, and those who have higher levels of glucose intolerance, he said.
"If someone is at high risk, then I would, in addition to trying to get them to lose weight and exercise, recommend medication, and personally, I favor pioglitazone. If you can really lose 30 pounds -- or whatever it is you need to lose -- then you might be able to discontinue the medication," said DeFronzo. "It's important to intervene early, rather than later, to save beta cell function."
Learn more about prediabetes from the American Diabetes Association.
Posted: March 2011