Xenical Publication Review 37-38

Rev Endocr Metab Disord. 2001 Oct;2(4):403-18.
Drug treatment of obesity.

Bray GA.

Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, Louisiana 70808, USA.

At present only two drugs are approved for long-term treatment of obesity. Sibutramine inhibits the reuptake of serotonin and norepinephrine. In clinical trials it produces a dose-dependent 5-10% decrease in body weight. Its side effects include dry mouth, insomnia, asthenia, and constipation. In addition, sibutramine produces a small increase in blood pressure and pulse that is a contraindication to the use of this drug in some individuals with heart disease. Xenical is the other drug approved for long-term use in the treatment of obesity. It works by blocking lipase and thus increasing the fecal loss of triglyceride. One valuable consequence of this mechanism of action is the reduction of serum cholesterol that averages about 5% more than can be accounted for by weight loss alone. In clinical trials it produces a 5-10% loss of weight. Its side effects are entirely due to undigested fat in the intestine that can lead to increased frequency and change in the character of stools. It can also lower fat-soluble vitamins. The ingestion of a vitamin supplement before bedtime is a reasonable treatment strategy. The effect on weight loss during long-term trials with these two drugs is shown in Figs 7 and 8 above. Also in this figure is data on phentermine used in trials of six months or more. Although there were differences in mean weight losses with these drugs, when the placebo effect was taken into account they all had a surprisingly similar magnitude of weight loss.

PMID: 11725727 [PubMed - indexed for MEDLINE]

Control Clin Trials. 2001 Oct;22(5):515-25.
Principles for enhanced recruitment of subjects in a large clinical trial. the XENDOS (XENical in the prevention of Diabetes in Obese Subjects) study experience.

Torgerson JS, Arlinger K, Käppi M, Sjöström L.

Department of Body Composition and Metabolism, Sahlgrenska University Hospital, Göteborg, Sweden.

In most clinical trials it is problematic to recruit enough patients within a reasonable time period. Prolonged or inefficient recruitment or both can have negative scientific and economic consequences. The XENDOS (XENical in the prevention of Diabetes in Obese Subjects) study is an ongoing randomized, double-blind, placebo-controlled, prospective, multicenter trial investigating whether orlistat combined with hypocaloric diet and moderate physical exercise can reduce the incidence of diabetes in obese subjects. To implement the XENDOS protocol and recruit the study patients, we designed a system for centralized patient recruitment and centralized scheduling of patients and staff at the 22 collaborating centers. The recruitment and inclusion phase was divided into a series of different consecutive examinations of increasing complexity. Relatively simple initial examinations enabling a large throughput of patients were followed by more detailed examinations of fewer subjects, by then known to fulfil some of the study-specific requirements. With the aid of object-oriented techniques, the software was modularized to enable concurrent engineering. We also selected a structure where plug-in modules handling specific tasks could be added to the system as needed. The design was supported by a flow-oriented view of the progress of the patients through the study. With this overall solution we managed to include 3305 subjects (98.8% of the requested number) within less than 4 months. The sex distribution (44.8% men) and the number of patients with impaired glucose tolerance (IGT), (21.1%) were in close accordance with, or far better than, the requirements of the protocol (45% men, at least 10% IGT patients). The basic design of the XENDOS information system can be adapted to fulfil the requirements of other study protocols within the fields of obesity, diabetes, hypertension, coronary heart disease, etc. Shortening the recruitment and inclusion phase of large clinical trials is of great value both to be medical society and the pharmaceutical industry.

PMID: 11578785 [PubMed - indexed for MEDLINE]