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Orlistat Shown to Cut Diabetes Risk: Presented at ICO

By Larry Schuster
Special to DG News


SAO PAULO, BRAZIL -- August 27, 2002 -- The modest weight loss induced by the obesity drug Xenical appears to delay onset of diabetes among obese patients at risk of developing the disease, according to study results released Monday.

Also known as orlistat, the drug appeared to cut in half the risk of diabetes in obese patients who had impaired glucose tolerance (IGT) over a four-year period, researchers announced at the 9^th International Congress on Obesity. In the study, the first to look at the capacity of a weight-loss drug to prevent type 2 diabetes, the reduction in risk appeared to beyond what would be expected by lifestyle changes alone.

The four-year XENDOS study enrolled 3304 obese patients with body mass at least 30 kg/m² at 22 centres in Sweden. Of the total, 1649 were randomized to receive orlistat 120 mg. plus a reduced fat diet and lifestyle modification, and 1655 received placebo and the diet and modifications alone.

At four years, the cumulative incidence of diabetes, as determined by a two-hour oral glucose tolerance test, was significantly lower in the orlistat group (6.2 percent) compared to the placebo group (9 percent; p = 0.0032).

Principle investigator Dr. Lars Sjostrom, of Sahlgrenska University Hospital, Gothenburg, Sweden, said the drug's anti-diabetes effect was observed only among the 21 percent of the study population with IGT. (Also involved in the study were researchers from Hoffmann-La Roche, Inc., Nutley, New Jersey, United States, which manufactures the drug.)

Of those in the IGT group, about nine percent developed diabetes by the end of the four-year study period. By contrast, of those who participated only in lifestyle management but did not take the drug, about 18 percent developed diabetes.

However, Dr. Sjostrom said, the researchers were unable to find that the drug offered any reduced risk among the obese participants of the study who had normal glucose tolerance. Few of these developed diabetes during the study period, whether they were on the drug or not.

About 20 million people in the United States have IGT, according to the National Health and Nutritional Examination Survey III. Up to one in 10 persons with IGT will develop diabetes per year. The risk of getting diabetes rises as people become more overweight and more sedentary, have a stronger family history of diabetes, and belong to an "at-risk" racial or ethnic minority group, according to the Joslin Diabetes Center, Harvard, University.

Xenical was approved in 1998 in the United States and is licensed for weight management in 149 countries, with 13.5 million patient treatments worldwide, according to drug's manufacturer. orlistat, the first prescription treatment for obesity that does not act as an appetite suppressant, works by interfering with the action of gastrointestinal (GI) lipase in the GI tract. As a result of this mechanism of action, 30 percent of ingested dietary fat is not absorbed.

Dr. Sjostrom said he believed the study results show that there was a substantial health benefit from the very modest loss in weight that was sustained for the four years. After four years in the study, those on the drug plus lifestyle management lost a total of 6.9 kilograms compared to their starting weight when they entered the study. Those on placebo and lifestyle management had shed 4.1 kilograms after four years.

In fact, he said, the amount of weight lost after the first year was higher than at four years, with 11.4 kilograms lost among those on the drug and 7.4 kilograms among the placebo group.

He said, "Many authorities don't think it's great difference either" in weight loss. "It has been claimed that two or three kilograms is of no biological importance. But the XENDOS study demonstrates with respect to diabetes there is, astonishingly enough."

Still, the modest weight loss came after a substantial investment by participants. All participants were instructed to have a diet that was 800 kilocalories less than would be required to maintain their current weight. They were asked to walk one kilometer more than they otherwise would walk per day, and they all had individualized counseling, usually with a dietitian every second week for six months, and then every month for the remaining three and a half years of the study.

Based on the findings, he said, "Certainly I wouldn't give it for diabetes prevention for people with normal glucose." But he added that there are other health benefits to the drug that argue in favor of using it as part of a weight-loss management program. He said the study also found that blood pressure, total cholesterol and low density lipid cholesterol were all improved in the Xenical group.

The Xenical study is the latest in a string of studies designed to look at diabetes prevention by either lifestyle alone or lifestyle and drug therapy. Findings from the study support those from two other studies, published this year and last in the New England Journal of Medicine, which demonstrated that lifestyle alone can reduce the incidence of diabetes by 58 percent. But the Xenical study demonstrated the strongest effect yet of a drug on reducing the risk of diabetes in an at-risk obese population.

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