An experimental pill that controls blood fats as well as blood sugar could be a better treatment for diabetics with high cholesterol even though side effects may be worse than current drugs, researchers.
If approved by regulators, Pargluva, or muraglitazar, would be the first insulin sensitizer to also target lipids. The drug is being developed by Bristol-Myers Squibb and Merck & Co. Inc.
“Most people with diabetes have hypertension and a variety of lipid disorders ... that’s why they develop complications, particularly cardiovascular disease,” Dr. Richard Kahn, the American Diabetes Association’s chief scientific and medical officer, said.
Other insulin sensitizers commonly used to treat type 2 diabetes include GlaxoSmithKline Plc’s Avandia and Takeda Pharmaceutical Co.’s Actos, or pioglitazone.
More than 18 million Americans have diabetes, a disease in which the body does not produce enough insulin or cells ignore the insulin, which is needed to convert food into energy. The condition can lead to debilitating or fatal complications such as heart disease, blindness, kidney disease and amputations.
“Muraglitazar has been shown to lower blood glucose over two years and significantly lowers triglycerides and raises good cholesterol,” said Dr. David Kendall, study investigator and director of the diabetes center at the University of Minnesota Medical School.
Several muraglitazar studies were featured at a San Diego meeting of the diabetes association, including a 1,159-patient study comparing a five-milligram dose of the drug to a 30 mg dose of Actos in patients who were also taking the anti-diabetes drug metformin.
After 24 weeks, the muraglitazar group lowered blood glucose by 1.14 percent versus 0.85 percent for the Actos group. The experimental drug also lowered triglycerides by 28 percent versus 14 percent for Actos and raised good cholesterol by 19 percent, compared with 14 percent for Actos.
Side effects, however, appeared to be worse for Pargluva, with 9.2 percent of patients experiencing fluid retention, compared with 7.2 percent of Actos patients.
There were also three cases of heart failure in the Pargluva group, compared with one case in the Actos group.
Medication under review
Kendall said the drug’s benefits have to be weighed against any increased risk and noted that the overall incidence of heart failure for type 2 diabetics is about 1 percent per year.
“In a patient in need of these insulin sensitizers who has fairly profound elevation of triglycerides and low HDL, you may favor this compound,” the investigator said.
He also said Bristol-Myers and Merck would likely need to test their drug against a 45 mg dose of Actos -- the dose that now accounts for a about a third of the drug’s prescriptions --before they could claim superiority over Takeda’s pill.
“This is not a compound that blows pioglitazone out of the water,” the investigator said.
Bristol-Myers and Merck said a 26-week extension of the phase III trial showed that differences between Pargluva and Actos were maintained. There were two additional cases of heart failure, compared with one case for Actos, the companies said.
Takeda declined to comment on the trial results. “Each molecule has unique characteristics ... until we have the full manuscript we don’t have the details, said Dr. Mehmood Khan, head of medical and scientific affairs at Takeda Pharmaceuticals North America.
The company expects results in September from a study designed to show how well Actos works in preventing events such as stroke and heart attack in people with type 2 diabetes who are at high risk for cardiovascular disease.
The U.S. Food and Drug Administration is currently reviewing a marketing application for Pargluva.
