Fluoxetine, orlistat, and sibutramine can diabetics achieve significant weight loss

Fluoxetine, orlistat, and sibutramine can help patients with diabetes achieve statistically significant weight loss over 26 to 52 weeks.

But the magnitude of weight loss was modest, and the long-term health benefits and safety remain unclear, according to an article in the July 12 issue of the Archives of Internal Medicine, one of the JAMA/Archives journals.

According to information in the article, the prevalence of obesity in the United States increased from 12 percent in 1991 to 18 percent in 1998. Recent survey data indicate that 65 percent of Americans are overweight. The prevalence of diabetes mellitus is also rising, with an increase of 49 percent between 1990 and 2000. Among U.S. adults, 8.6 percent of those older than 20 have diabetes, one third of whom are undiagnosed. Obesity is closely related to type 2 diabetes, and weight reduction is an important part of the care delivered to obese people with diabetes.

Susan L. Norris, M.D., M.P.H., of the Centers for Disease Control and Prevention, Atlanta, Ga., and colleagues performed a meta-analysis to assess the efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes. A systematic review of the literature found sufficient data for the meta-analysis for the antidepressant drug fluoxetine and the weight loss medications orlistat and sibutramine. Fourteen randomized, placebo-controlled trials were included in the review, with a total of 2,231 patients.

"This meta-analysis provides evidence that fluoxetine, orlistat, and sibutramine can achieve modest but statistically significant short-term weight loss when used as a primary weight loss strategy," the authors report.

Fluoxetine produced weight reduction of 3.4 kilograms at eight to 16 weeks of follow-up; 5.1 kilograms at 24 to 30 weeks; and 5.8 kilograms at 52 weeks. Orlistat produced weight loss of 2.6 kilograms at 52 weeks. Sibutramine produced weight loss of 4.5 kilograms at up to 26 weeks.

Levels of glycated hemoglobin (measured by blood tests), which reflects overall control of diabetes and blood glucose levels, were also modestly reduced by fluoxetine (one percent at 8-16 weeks; one percent at 24 to 30 weeks; 1.8 percent at 52 weeks), orlistat (0.4 percent), and sibutramine (0.7 percent).

The three drugs were generally well tolerated and produced a low incidence of serious adverse events.

But the authors caution, "Since treatment duration was up to 52 weeks for fluoxetine and orlistat and 26 weeks for sibutramine, the long-term effects of these drugs on weight and health outcomes in persons with type two diabetes remain uncertain."

"Further work is needed to examine whether the combination of lifestyle modification and pharmacotherapy improves the efficacy of drug therapy, whether such combinations are synergistic or additive, and what dosage schedules and sequencing of the two interventions are optimal," they suggest. "The incidence of adverse events must be carefully monitored over the long term in diabetic populations, which already have multiple risk factors for major cardiovascular and neurologic events."

"The advancement of research in these areas will help reduce cardiovascular disease risk factors and events for persons with type two diabetes," the authors conclude.