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Volume 5, Issue 6 EFFECTIVE WEIGHT LOSS DRUGS
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Roche Pharmaceuticals announced on May 22, that the Food and Drug Administration (FDA) is reviewing the company's application to add a new indication for Xenical (orlistat) as an adjunct treatment for type 2 diabetes.
Roche submitted the supplemental new drug application to the FDA on March 19, 2001, based on the results of new clinical trials conducted in overweight and obese patients with type 2 diabetes. The clinical trial data show that patients treated with Xenical plus a mildly-reduced calorie diet lost more weight than those patients treated with placebo plus diet, and also had significantly greater and sustained decreases in glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG). Some of the favorable effects of Xenical treatment on glycemic control may be independent of weight loss, as decreases in FPG were observed as early as after two weeks of treatment -- before significant weight loss occurred. In addition, patients with type 2 diabetes treated with Xenical were able to reduce their daily dose of other antidiabetic medications, such as sulfonylureas, insulin, and metformin. Finally, gastrointestinal side effects that occur in patients taking Xenical were observed less frequently in patients with type 2 diabetes. The application was supported by findings from seven large multicenter, randomized, placebo-controlled trials involving 2,600 patients with type 2 diabetes. Four of the studies were one year and three were six months. Some of these trials are summarized in the abstracts below. The studies showed:
In addition, three 2-year studies were summarized in the Journal of the American Medical Association (JAMA) in May 2000. Author Steven B. Heymsfield of the Obesity Research Center at St. Luke's-Roosevelt Hospital Center pooled the results of 673 diabetic, glucose intolerant and healthy obese subjects given 120 mg orlistat or placebo 3 times a day. Subjects in the three studies were evaluated at 39 clinical research centers in the US and Europe between 1992 and 1995. Of the 673 recruited, 463 (69 percent) completed the trial. The drop out rate was similar in both groups. "Cross-over" subjects were not included in these results, only subjects who received orlistat or placebo for the full two years. Results.Individuals given orlistat lost significantly more weight than subjects who received placebo, and twice as many Xenical subjects with impaired glucose tolerance normalized after treatment compared to placebo. In addition, a smaller percentage of subjects in the Xenical group with impaired glucose tolerance at baseline progressed to diabetes. Weight loss. Xenical subjects lost 6.72 ± 4.1 kg during the study vs. 3.79 ± 0.38 for placebo. 52.9 percent of subjects given orlistat lost 5 percent or more, 30.1 percent lost 10 percent or more of initial body weight, whereas 37.7 percent of subjects given placebo lost 5 percent or more, and 16.5 percent lost 10 percent or more of initial body weight.
Glucose tolerance. Changes in glucose tolerance are shown in the table on the right. For subjects with abnormal glucose tolerance at baseline, those who received orlistat improved after treatment, whereas deterioration occurred in a greater proportion of subjects receiving placebo. For subjects with impaired glucose tolerance (IGT) at baseline, 71.6 percent treated with orlistat had normal glucose tolerance at the end of treatment, compared with 49.1 in the placebo group. Three percent of patients treated with orlistat progressed to diabetes, vs. 7.6 percent for placebo. Fasting glucose and insulin. Both glucose and insulin levels decreased more in orlistat treated patients who were in the normal or impaired groups. However, this was not the case in the group of diabetic patients. Researchers suggest that the lack of improvement among diabetic subjects given orlistat is due to the more severe beta-cell dysfunction in diabetic subjects assigned orlistat vs. placebo. At baseline the mean fasting insulin level was roughly 2-fold lower among diabetic orlistat subjects (97 ± 13 pmol/L vs. 179 ± 59 pmol/L). Conclusions.Significant improvements were seen in glucose tolerance, which supports the concept that modest weight loss may reduce the risk of developing type-2 diabetes. When the results of studies were pooled, glucose tolerance improved, and fewer subjects progressed to IGT and diabetes in the orlistat group. However, the number of subjects who progressed to diabetic status was very small, and further analysis of the trials is warranted to address this issue.
Note. Conference abstracts not available in public edition.
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