Study Confirms Long-Term Efficacy Of Meridia In Weight Loss, Maintenance

MT. OLIVE, NJ -- Feb. 25, 1999 --

A new study featured in this month's American Journal of Medicine confirms the efficacy of Knoll Pharmaceutical Co.'s Meridia(R) (sibutramine hydrochloride monohydrate) C-IV Capsules in helping obese patients achieve additional weight loss following a very-low-calorie diet and maintain their total weight loss for up to one year.

Additionally, weight loss of at least five percent or greater was accompanied by a decrease in waist circumference, a decrease in triglyceride levels and an increase in beneficial high-density lipoprotein (HDL) cholesterol compared to placebo.

"Very-low-calorie diets produce large initial weight loss, but are not very effective at achieving long-term maintenance of weight loss," said study investigator Olivier Ziegler, M.D., Ph.D., senior consultant in the department of nutrition and metabolic disease at the centre Hospitalo-Universitaire of Nancy in Nancy, France. "In this study, Meridia helped most people lose significantly more weight -- beyond the weight lost on the very-low-calorie diet alone -- and maintain that total weight loss for one year."

First-ever clinical guidelines for obesity treatment developed by National Heart Lung and Blood Institute (NHLBI) in 1998, indicate that waist circumference is an independent weight-related health risk over and above that of body mass index or BMI (weight in kg divided by height in m2). A central fat distribution, indicated by a large waist circumference (men greater than 40 inches or 102 centimetres; women greater than 35 inches or 88 centimetres), is particularly associated with an increased risk for type II diabetes, dyslipidemia, hypertension and cardiovascular disease for people with a BMI between 25 kg/m and 34.9 kg/m.

Patients taking Meridia had a six centimetre (1.5 inches) mean decrease in their waist circumference from screening to month 12, compared to only one centimetre (one-third of an inch) in the placebo group. These changes were associated with a significant increase in plasma HDL cholesterol and a decrease in triglyceride levels.

"Modest weight loss of just five to 10 percent and maintenance is associated with substantial improvements in obesity co-morbidities and when this is coupled with reduced waist circumference, obesity-related health risks are further decreased," Dr. Ziegler said. "So reducing excess abdominal fat and weight, can result in added health benefits."

The study was conducted in 12 medical centres throughout France and was designed to determine the efficacy of long-term treatment with Meridia in maintaining or improving weight loss in obese patients who had lost weight on a very-low-calorie diet. Study participants ranged from 18 to 55 in age with a BMI of greater than 30 kg/ m2. Following an initial screening, patients were put on a four-week very-low-calorie diet (220 to 800 kcal/daily). Patients who lost at least 12.2 lb. (6 kg) during the four-week period on the very-low-calorie diet were randomised into a 12-month double-blind placebo trial using Meridia. Of the 159 trial participants, 81 were assigned 10 mg of Meridia once daily and 78 received placebo. The very-low-calorie diet was stopped at the beginning of the double-blind treatment period. Patients received dietary counselling every three months and maintained a low-calorie diet.

The following study results encompass the screening period through trial completion:
-- 86 percent of Meridia patients had lost at least five percent of their total body weight (compared to 55 percent in placebo group)
-- 54 percent lost at least 10 percent (compared to 23 percent receiving placebo)
-- 17 percent lost 20 percent or more of their body weight (compared to three percent taking placebo).

The majority of patients taking Meridia maintained the weight loss from the very-low-calorie diet as well as the additional weight loss for one year. At month 12, 75 percent of study participants taking Meridia had maintained all their weight loss, 95 percent maintained at least 50 percent and 96 percent maintained 25 percent of their weight loss. Study participants had a 97 percent rate of compliance to the study regimen.

Meridia is indicated for the management of obesity, including weight loss and maintenance of weight loss when used in conjunction with a reduced-calorie diet. Meridia is recommended for patients with an initial BMI 30 kg/m2 or 27 kg/m2 in the presence of other risk factors (for example hypertension and diabetes).

In clinical trials of 6,000 individuals, including 4,000 obese patients, Meridia has been shown to be a safe and effective product. Meridia is a well-tolerated medication. Most side effects with Meridia are mild and temporary and include dry mouth, headache, insomnia and constipation. Some people taking Meridia experienced substantial increases in blood pressure and for this reason regular blood pressure monitoring is required when taking Meridia. These blood pressure increases generally occur early in treatment and the prescribing physician may decide to decrease the dose of Meridia or discontinue the medication.

In clinical trials, the number of patients who discontinued Meridia use because of hypertension was less than one-half of one percent and was comparable to placebo. Meridia should be given with caution to those patients with a history of hypertension and should not be given to patients with uncontrolled or poorly-controlled hypertension.

As a centrally acting prescription anti-obesity medication, Meridia is classified as a schedule IV drug.