In a clinical study, Keck School of Medicine of USC (University of Southern California) researchers have found that pioglitazone, a drug that reverses some of the bad effects of obesity, reduced the risk of type 2 diabetes by 72 per cent in pre-diabetic patients. The researchers also found that the drug slowed the development of an early marker of cardiovascular disease in the carotid arteries.
Dr Thomas A Buchanan, professor of medicine, obstetrics and gynaecology, and physiology and biophysics at Keck School of Medicine, was a co-investigator of the study, along with two other of the school’s researchers — Dr Howard N Hodis, the Harry Bauer & Dorothy Bauer Rawlings Professor of Cardiology, and Dr Wendy J Mack, associate professor of preventive medicine. The lead investigator was Dr Ralph A DeFronzo of University of Texas at San Antonio.
Patients who are pre-diabetic have impaired glucose tolerance, which also is associated with increased risk of cardiovascular disease. In the study of 602 patients, 2.1 per cent of participants who received pioglitazone developed type 2 diabetes, compared to 7.6 per cent of participants given a placebo. In addition, 48 per cent of drug-treated participants saw their glucose tolerance levels return to normal, compared to 28 per cent of those who received a placebo.
Pioglitazone is one of a class of drugs called thiazolidinediones, which Dr Thomas A Buchanan has been investigating for more than 15 years. “One way these drugs improve glucose tolerance is by taking fat from the liver, muscle and abdomen and moving it to under the skin, where it is less dangerous,” he says. “Patients on pioglitazone gained some weight – an average of eight pounds compared to two pounds for the placebo group. Some of the weight gain was water and some was fat. However, metabolically they acted as if they had lost weight because it was in a better place.”
In examining pioglitazone’s effect on the development of cardiovascular disease, the researchers found that it slowed the development of atherosclerosis, or thickening, of the carotid artery. The carotid thickness for those in the study who received the drug was 31 per cent less than the placebo group. Dr Howard N Hodis developed the ultrasound method of measuring the thickness, and he and Dr Wendy J Mack applied that method to the study’s subjects.
The glucose and cardiovascular results of the study confirmed the findings of research on thiazolidinediones by Dr Thomas A Buchanan and his USC team between 1995 and 2000. They conducted the first US studies of troglitazone, finding that it delayed or prevented the development of diabetes by 55 per cent. Sold under the brand name of Rezulin, troglitazone was taken off the market because it was found to cause liver damage in rare cases. Two other thiazolidinediones then were developed – rosiglitazone and pioglitazone.
“We expect this most recent study will encourage doctors to use pioglitazone early in the treatment of diabetes,” Dr Thomas A Buchanan says, “because the study results make a strong case that such early use will keep the disease from getting worse.”