Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: A randomized controlled trial

Chicago Center for Clinical Research, Ill, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 02/1999; 281(3):235-42.
Source: PubMed


Orlistat, a gastrointestinal lipase inhibitor that reduces dietary fat absorption by approximately 30%, may promote weight loss and reduce cardiovascular risk factors.
To test the hypothesis that orlistat combined with dietary intervention is more effective than placebo plus diet for weight loss and maintenance over 2 years.
Randomized, double-blind, placebo-controlled study conducted from October 1992 to October 1995.
Obese adults (body mass index [weight in kilograms divided by the square of height in meters], 30-43 kg/m2) evaluated at 18 US research centers.
Subjects received placebo plus a controlled-energy diet during a 4-week lead-in. On study day 1, the diet was continued and subjects were randomized to receive placebo 3 times a day or orlistat, 120 mg 3 times a day, for 52 weeks. After 52 weeks, subjects began a weight-maintenance diet, and the placebo group (n = 133) continued to receive placebo and orlistat-treated subjects were rerandomized to receive placebo 3 times a day (n = 138), orlistat, 60 mg (n = 152) or 120 mg (n = 153) 3 times a day, for an additional 52 weeks.
Body weight change and changes in blood pressure and serum lipid, glucose, and insulin levels.
A total of 1187 subjects entered the protocol, and 892 were randomly assigned on day 1 to double-blind treatment. For intent-to-treat analysis, 223 placebo-treated subjects and 657 orlistat-treated subjects were evaluated. During the first year orlistat-treated subjects lost more weight (mean +/- SEM, 8.76+/-0.37 kg) than placebo-treated subjects (5.81+/-0.67 kg) (P<.001). Subjects treated with orlistat, 120 mg 3 times a day, during year 1 and year 2 regained less weight during year 2 (3.2+/-0.45 kg; 35.2% regain) than those who received orlistat, 60 mg (4.26+/-0.57 kg; 51.3% regain), or placebo (5.63+/-0.42 kg; 63.4% regain) in year 2 (P<.001). Treatment with orlistat, 120 mg 3 times a day, was associated with improvements in fasting low-density lipoprotein cholesterol and insulin levels.
Two-year treatment with orlistat plus diet significantly promotes weight loss, lessens weight regain, and improves some obesity-related disease risk factors.

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    • "At present, however, pharmacotherapy options for obesity are limited, and there have been concerns over the long-term efficacy and safety of antiobesity drugs (Li and Cheung 2009). In Europe, there are no centrally acting drugs on the market, and treatment is limited to the lipase inhibitor, Orlistat (Xenical®; Alli®), which works by preventing the breakdown and absorption of fat in the intestinal system (Davidson et al. 1999). The Food and Drug Administration (FDA) in the USA has recently approved the introduction of two new anti-obesity drug treatments, the 5- HT 2C receptor agonist Lorcaserin (Belviq®) and a combination therapy of phentermine and topiramate (Qsymia®). "
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    ABSTRACT: The treatment of obesity is an increasing global health priority, yet few effective drug treatments are currently available. The discovery of novel anti-obesity therapies could be assisted by the validation of experimental (translational) medicine models in healthy volunteers that assess efficacy and safety at an early stage of drug development. The aim of this study was to examine the effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) in an experimental medicine model assessing both appetite and mood. Using a between-subjects, double-blind, placebo-controlled design, 24 male and 24 female participants were randomly assigned to either placebo, 15- or 30-mg mCPP treatment groups. Lunch was eaten from a Universal Eating Monitor (UEM) that measured eating rate, and the participants completed the P1vital® Oxford Emotional Test Battery (ETB) and a series of appetite and mood ratings. mCPP reduced appetite and, in women, enhanced measures of satiation. The drug also enhanced memory for emotional material in the word recall and recognition memory tasks of the ETB. The results provide new insight into the effects of mCPP on appetite, satiety and memory in humans. In addition, our data provide an illustration of the value of measuring changes in appetite and mood in healthy volunteers to determine the potential efficacy and safety of novel anti-obesity drugs.
    Psychopharmacology 01/2014; 231(12). DOI:10.1007/s00213-013-3409-x · 3.88 Impact Factor
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    • "Low-carbohydrate diets and calorie-restricted low-fat diets both produce clinically meaningful reductions in weight (Nordmann et al., 2006; Hession et al., 2009) and weight-loss medications such as orlistat can provide an additional 3–4 kg of weight-loss benefit beyond dietary change alone (Sj€ ostr€ om et al., 1998; Davidson et al., 1999; Hauptman et al., 2000). However, individuals' ability to make an informed decision among competing options is limited by a lack of data indicating which individuals may experience the greatest benefit from each weight-loss approach. "
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    ABSTRACT: Identifying pretreatment dietary habits that are associated with weight-loss intervention outcomes could help guide individuals' selection of weight-loss approach among competing options. A pretreatment factor that may influence weight-loss outcomes is macronutrient intake. Overweight and obese Durham Veterans Affairs outpatients were randomised to a weight-loss intervention with a low-carbohydrate diet (n = 71) or orlistat medication therapy plus a low-fat diet (n = 73). Percentage fat, carbohydrate and protein intake prior to treatment were measured using 4-day food records. Linear mixed-effects models were used to determine whether pretreatment percentage macronutrient intake influenced weight trajectories and weight loss in each weight-loss condition. Participant's mean age was 53 years, baseline body mass index was 39.3 kg m(-2) and 72% were male. A higher pretreatment percentage carbohydrate intake was associated with less rapid initial weight loss (P = 0.02) and less rapid weight regain (P = 0.03) in the low-carbohydrate diet condition but was not associated with weight trajectories in the orlistat plus low-fat diet condition. In both conditions, a higher pretreatment percentage fat intake was associated with more rapid weight regain (P < 0.01). Pretreatment percentage protein intake was not associated with weight trajectories. None of the pretreatment macronutrients were associated with weight loss on study completion in either condition. Selection of a weight-loss approach on the basis of pretreatment macronutrient intake is unlikely to improve weight outcomes at the end of a 1-year treatment. However, pretreatment macronutrient intake may have implications for tailoring of interventions to slow weight regain after weight loss.
    Journal of Human Nutrition and Dietetics 11/2013; 28(s2). DOI:10.1111/jhn.12188 · 1.99 Impact Factor
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    • "moderate in nature (Davidson et al., 1999; Torgerson et al., 2004). Significant decreases in fat-soluble vitamins (A, D, E, K1) in the orlistat group occurred when compared with placebo (Torgerson et al., 2004); however, the mean level of each vitamin assessed was within the reference range during the 4-year study. "
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    ABSTRACT: Moderate weight loss (>5%), which has been associated with improvements in glycemic parameters in patients with dysglycemia, also reduces the presence of other comorbidities, including dyslipidemia and hypertension, culminating in a reduced risk of cardiovascular disease. Lifestyle changes are the recommended preliminary approach to weight loss, with an initial weight-loss goal of 10% of body weight achieved over 6 months at a rate of 1-2 pounds per week selected as an appropriate target to decrease the severity of obesity-related risk factors. Implementing and maintaining the lifestyle changes associated with weight loss can, however, be challenging for many patients. Therefore, additional interventions sometimes may be necessary. Bariatric surgery can also be a highly effective option for weight loss and comorbidity reduction, but surgery carries considerable risks and is still applicable only to selected patients with type 2 diabetes. Thus, attention is turning to the use of weight-loss medications, including 2 recently approved compounds: twice-daily lorcaserin and a once-daily combination of phentermine and topiramate extended-release, both shown to be safe and effective therapies in the management of obesity in patients with type 2 diabetes.
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