Dose-ranging study of an orlistat tablet formulation.

OBJECTIVE: Examine inhibition of dietary fat absorption with orlistat tablets (24, 36, 48, 72, and 144 mg) vs. 60-mg orlistat capsule. MATERIALS AND METHODS: 83 overweight/obese subjects randomized to 1 of 6 open-label treatments. Pre- vs. post-treatment fecal fat analysis was conducted. RESULTS: Mean percent fecal fat (60-mg capsule, 16.8%; 48-mg tablet, 16.5%) was similar (ratio of geometric mean and 90% CI: 60-mg capsule/48-mg tablet, 1.05 (0.79, 1.39)). Fecal fat excretion was ~2.5 times greater with 144-mg vs. 24-mg tablets. No new safety concerns emerged. CONCLUSION: Dietary fat excretion increases with increasing orlistat tablet dose.
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Pharmacologic and Pharmacodynamic Equivalence of 2 Formulations of Orlistat.

We sought to establish the bioequivalence of 2 weight-loss aids: orlistat 27-mg chewable tablet and orlistat 60-mg capsule, measured pharmacodynamically as percentage fecal fat excretion. Two open-label, single-center, randomized, 3-period, 3-treatment crossover studies were conducted in adults with body mass index 25-33 kg/m2 . For each 9-day treatment period, subjects received orlistat 27-mg chewable tablet, 60-mg capsule, or 120-mg capsules (2 60-mg capsules) 3 times daily; a 2-day washout separated treatments. Primary bioequivalence analyses were based on 2 1-sided tests of the 90% CI of the ratio of geometric means using log-transformed data (study 1) and by the dose-scale method to calculate bias-corrected and accelerated 90% CI of relative bioavailability (f) using nontransformed data (study 2). Bioequivalence was established if 90% CIs fell within 0.80-1.25. In total, 48 and 144 subjects were randomized in study 1 and study 2, respectively. Bioequivalence between the formulations was established in both studies: study 1 ratio of geometric means of percentage fecal fat excretion was 0.96 (2 1-sided tests, 90% CI 0.87-1.06); study 2-point estimate of f was 1.09 (bias-corrected and accelerated 90% CI 0.98-1.22). Tolerability of the 27-mg tablet was consistent with the 60-mg capsule; mild gastrointestinal effects were most common.

Orlistat 60 mg reduces visceral adipose tissue: a 24-week randomized, placebo-controlled, multicenter trial.

It is well established that abdominal obesity or upper body fat distribution is associated with increased risk of metabolic and cardiovascular disease. The purpose of the present study was to determine if a 24 week weight loss program with orlistat 60 mg in overweight subjects would produce a greater change in visceral adipose tissue (VAT) as measured by computed tomography (CT) scan, compared to placebo. The effects of orlistat 60 mg on changes in total fat mass (EchoMRI-AH and BIA), ectopic fat (CT) and glycemic variables were assessed. One-hundred thirty-one subjects were randomized into a multicenter, double-blind placebo controlled study in which 123 subjects received at least one post baseline efficacy measurement (intent-to-treat population). Both orlistat-and placebo-treated subjects significantly decreased their VAT at 24 weeks with a significantly greater loss of VAT by orlistat treated subjects (-15.7% vs. -9.4%, P < 0.05). In addition, orlistat-treated subjects had significantly greater weight loss (-5.93 kg vs. -3.94 kg, P < 0.05), total fat mass loss (-4.65 kg vs. -3.01 kg, P < 0.05) and trended to a greater loss of intermuscular adipose tissue and content of liver fat compared with placebo-treated subjects. This is the first study to demonstrate that orlistat 60 mg significantly reduces VAT in addition to total body fat compared to placebo treated subjects after a 24 week weight loss program. These results suggest that orlistat 60 mg may be an effective weight loss tool to reduce metabolic risk factors associated with abdominal obesity.

Compliance, behavior change, and weight loss with orlistat in an over-the-counter setting.

OBJECTIVE: The study was conducted to provide information on how consumers would use orlistat 60 mg, especially in terms of product dosing, in a setting without physician supervision. METHODS AND PROCEDURES: A 3-month, open-label, naturalistic study was conducted in an over-the-counter (OTC) setting in 18 pharmacies. Consumers >/=18 years were allowed to purchase orlistat packages containing a bottle of orlistat 60 mg plus educational materials, which provided lifestyle information and tools to encourage successful weight loss. Data were collected at pharmacy visits and during telephone interviews at 14, 30, 60, and 90 days after enrollment. RESULTS: A total of 237 subjects purchased and used the product, and completed at least one interview. Most subjects followed the dosing directions and took two to three capsules per day with meals throughout the study. The majority of subjects took a daily multivitamin, as directed. Approximately, 80% of subjects used the educational materials and found them useful or very useful. Over the study duration, most subjects reported following a diet and 51% of subjects reported more frequent or longer exercise than at enrollment. Approximately, 80% of subjects indicated they were satisfied or very satisfied with the weight loss achieved; measured and self-reported relative median weight loss was approximately 5% after > or =60 days of using orlistat. Most common adverse events were gastrointestinal (GI), and majority of subjects did not interrupt or discontinue orlistat due to these GI events. DISCUSSION: These results demonstrate that orlistat 60 mg can be used appropriately and safely and with high consumer satisfaction without physician supervision or dietary counseling. Collectively, results indicate that orlistat 60 mg is an appropriate weight loss therapy in the OTC environment.

Low-dose orlistat effects on body weight of mildly to moderately overweight individuals: a 16 week, double-blind, placebo-controlled trial.

BACKGROUND: Lifestyle measures are considered the first line of therapy for treating overweight individuals, but many are unable to achieve a meaningful weight loss. OBJECTIVE: To determine the efficacy and safety of orlistat 60 mg, given 3 times daily, for weight loss in mildly to moderately overweight individuals. METHODS: A multicenter, 16 week, randomized, double-blind, placebo-controlled study was conducted in 391 overweight subjects at 20 US centers. The main outcome measure was change in weight from baseline to week 16; secondary measures included changes in body mass index, waist circumference, blood pressure, and fasting lipoprotein and glucose levels. RESULTS: Subjects in both groups lost weight over the treatment period; however, orlistat-treated subjects lost significantly more weight than placebo-treated subjects beyond 2 weeks of treatment. Weight loss from baseline to week 16 was significantly greater in participants receiving orlistat versus those receiving placebo (3.05 vs 1.90 kg; p < 0.001, intent-to-treat analysis). Orlistat-treated subjects who completed 16 weeks of treatment lost 4.8 +/- 0.35% (mean +/- SE) of baseline weight compared with 3.1 +/- 0.38% for the placebo group (p < 0.001). Orlistat-treated subjects, compared with those receiving placebo, also demonstrated a greater relative reduction in total (-4.4% vs 0.0%; p = 0.004) and low-density lipoprotein cholesterol (-7.2% vs -0.6%; p = 0.005) and both diastolic (-3.9% vs -0.5%; p = 0.001) and systolic blood pressure (-4.7% vs -1.8%; p = 0.004). Both groups showed a similar safety profile; gastrointestinal events were significantly more common in the orlistat-treated subjects. CONCLUSIONS: The use of orlistat 60 mg by mildly to moderately overweight individuals produced significant weight loss in conjunction with a reduced calorie diet and self-instructional materials. This amount of weight loss was associated with improvements in several weight-related risk factors. Orlistat 60 mg may be a useful adjunct to lifestyle measures and has the potential to contribute significantly to weight and risk factor improvement for overweight individuals.