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Review the following articles for more information and findings on health risks of obesity, benefits
of weight loss and the efficacy of XENICAL.
Articles
Click on the following links to view the summary of the article.
Orlistat and Obese Patients With Type 2 Diabetes
Orlistat and Prevention of Type 2 Diabetes
Orlistat, Weight Loss, and the Prevention of Weight Regain
Orlistat, Glucose Tolerance and Progression to Type 2 Diabetes
New Dietary Guidelines Announced
"Role of orlistat in the treatment of obese patients
with type 2 diabetes." 
PA Hollander, et al. Diabetes Care. 1998; 21:1288-1294.
Objective: Obesity is an important risk factor for type 2 diabetes. Weight loss in patients with type 2
diabetes is associated with improved glycemic control and reduced cardiovascular disease risk factors,
but weight loss is notably difficult to achieve and sustain with caloric restriction and exercise. The
purpose of this study was to assess the impact of treatment with orlistat, a pancreatic lipase inhibitor,
on weight loss, glycemic control, and serum lipid levels in obese patients with type 2 diabetes on
sulfonylurea medications.
Research Design and Methods: In a multicenter 57-week randomized double-blind placebo-controlled study,
120 mg of orlistat or placebo was administered orally three times a day with a mildly hypocaloric diet
to 391 obese men and women with type 2 diabetes who were aged >18 years, had a BMI of 28-40 kg/m2, and
were clinically stable on oral sulfonylureas. Changes in body weight, glycemic control, lipid levels,
and drug tolerability were measured.
Results: After 1 year of treatment, the orlistat group lost 6.2 + 0.45% (mean + SEM) of initial body
weight vs. 4.3 + 0.49% in the placebo group (P<0.001). Twice as many patients receiving orlistat (49% vs. 23%) lost > 5% of initial body weight (P<0.001). Orlistat treatment plus diet compared with placebo plus diet was associated with significant improvement in glycemic control, as reflected in decreases in HbA1c (P<0.001) and fasting plasma glucose (P<0.001) and in dosage reductions of oral sulfonylurea medication (P<0.01). Orlistat therapy also resulted in significantly greater improvements than placebo in several lipid parameters; namely, greater reductions in total cholesterol, (P<0.001), LDL cholesterol (P<0.001), triglycerides (P<0.05), apolipoprotein B (P< 0.001) and the LDL/HDL cholesterol ratio (P<0.001). Mild-to-moderate and transient gastrointestinal events were reported with orlistat therapy, although their association with study withdrawal was low. Fat-soluble vitamin levels generally remained within the reference range, and vitamin supplementation was required in only a few patients.
Conclusions: Orlistat is an effective treatment modality in obese patients with type 2 diabetes, with
respect to clinically meaningful weight loss and maintenance of weight loss, improved glycemic control,
and improved lipid profile.
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"Orlistat and Prevention of Type 2 Diabetes"
Objective: The purpose of this study was to determine if orlistat, as compared to placebo, could prevent or delay the development of type 2 diabetes in obese, non-diabetic patients and to determine the long-term weight control following treatment with 120-mg orlistat compared to placebo when administered. This study also assessed the effects of treatment on several obesity-related risk factors including total cholesterol, LDL, HDL, LDL/HDL ratio, fasting insulin, fasting glucose, systolic and diastolic blood pressure, pulse rate and waist circumference and determined the safety and tolerability of orlistat for up to 4 years...
Study Design: In a multi-center 209-week randomized double-blind placebo-controlled parallel design study, 120 mg of orlistat or placebo was administered orally 3 times a day with a mildly hypocaloric diet to 3304 obese male and female patients with either normal (n=2643) or impaired glucose (n=661) tolerance at baseline. Patients ranged in age from 30 to 60 years with a BMI at baseline of >30 kg/m2.
Results: Orlistat significantly (p<0.01) delayed the onset of type 2 diabetes such that at the end of 4 years of treatment the cumulative rate of diabetes in the overall study population was 8.3% for the placebo group compared to 5.5% for the orlistat group with a relative risk reduction of 34%. For patients with impaired glucose tolerance at baseline, the relative risk reduction for developing type 2 diabetes was 42%.
Following the first year of treatment 73% of the orlistat treated patients and 45% of the placebo patients lost >5% of their baseline body weight, and 41% of the orlistat patients and 21% of the placebo patients lost >10% of their baseline body weight. Following 4 years of treatment, 45% and 21% of the orlistat treated patients and 28% and 10% of the placebo patients lost >5% and >10% of their baseline body weight respectively.
Throughout the 4-year treatment period, orlistat-treated compared to placebo-treated patients had statistically significant (p<0.05) reductions several obesity related metabolic risk factors including BMI, total cholesterol, LDL cholesterol, LDL/HDL ratio, fasting glucose, systolic blood pressure, diastolic blood pressure, pulse rate, plasminogen activator inhibitor and waist circumference.
Conclusions: This 4-year study showed that orlistat prevented/delayed the onset of type 2 diabetes in obese, non-diabetic patients. Treatment with orlistat also resulted in significant weight loss and improvement in obesity-related risk factors, which were maintained over the 4-year treatment period. The safety and tolerability profile of orlistat, previously established for up-to 2 years of treatment, is now extended to 4 years with no evidence of worsening tolerability over time.
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“Randomized placebo-controlled trial of orlistat for weight loss and prevention of weight regain
in obese patients”
Sjöström, L. et al. Lancet. 1998, 352:167-173.
Background: We undertook a randomized controlled trial to assess the efficacy and tolerability of
orlistat, a gastrointestinal lipase inhibitor, in promoting weight loss and preventing weight regain
in obese patients over a 2-year period.
Methods: 743 patients (body mass index 28-47 kg/m2), recruited at 15 European centres, entered a 4-week,
single-blind, placebo lead-in period on a slightly hypocaloric diet (600 kcal/day deficit); 688
patients who completed the lead-in were assigned double-blind treatment with orlistat 120 mg (3
times a day) or placebo for 1 year in conjunction with the hypocaloric diet. In a second 52-week
double-blind period patients were reassigned orlistat or placebo with a weight maintenance (eucaloric)
diet.
Findings: From the start of lead-in to the end of year 1, the orlistat group lost, on average, more
bodyweight than the placebo group (10.2% [10.3 kg] vs. 6.1% [6.1 kg]; LSM difference 3.9 kg [P<0.001] from randomization to the end of year 1). During year 2, patients who continued with orlistat regained, on average, half as much weight as those patients who switched to placebo (P<0.001). Patients who switched from placebo to orlistat lost an additional 0.9 kg during year 2, compared with a mean regain of 2.5 kg in patients who continued on placebo (P<0.001). Total cholesterol, low-density lipoprotein (LDL) cholesterol, the LDL/high-density lipoprotein ratio, and concentrations of glucose and insulin decreased more in the orlistat group than in the placebo group. Gastrointestinal adverse events were more common in the orlistat group. Other adverse symptoms occurred at a similar frequency during both treatments.
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"Effects of weight loss with orlistat on glucose tolerance and progression to type 2 diabetes in obese adults."
Heymsfield SB, et al. Archives of Internal Medicine, 2000; 160:1321-1326. Available at: http://archinte.ama-assn.org/issues/v160n9/ffull/ioi90351.html.
Background: Orlistat is a gastrointestinal lipase inhibitor that reduces dietary fat absorption by
approximately 30%, promotes weight loss, and may reduce the risk of developing impaired glucose
tolerance and type 2 diabetes in obese subjects.
Objective: To test the hypothesis that orlistat combined with dietary intervention improves glucose
tolerance status and prevents worsening of diabetes status more effectively than placebo.
Methods: We pooled data from 675 obese (body mass index 30-43 kg/m2) adults at 39 US and European
research centers in 3 randomized, double-blind, placebo-controlled multicenter clinical trials.
Subjects received placebo plus a low-energy diet during a 4-week lead-in period. On study day 1,
the diet was continued, and subjects were randomized to receive placebo 3 times a day (n=316) or
treatment with orlistat, 120 mg 3 times a day (n=359), for 104 weeks. A standard 3-hour oral glucose
tolerance test was performed on day 1 and at the end of treatment.
Main Outcome Measures: The categorical assessment of glucose tolerance status (normal, impaired,
diabetic) and changes in status from randomization to end of treatment were the primary efficacy
measures. The secondary measures were fasting and postchallenge glucose and insulin levels.
Results: The mean length of follow-up was 582 days. Subjects who were treated with orlistat lost
more weight (mean + SEM, 6.72 + 0.41 kg from initial weight) than subjects who received placebo
(3.79 + 0.38 kg; P<0.001). A smaller percentage of subjects with impaired glucose tolerance at baseline progressed to diabetic status in the orlistat (3.0%) vs. placebo (7.6%) group. Conversely, among subjects with impaired glucose tolerance at baseline, glucose levels normalized in more subjects after orlistat treatment (71.6%) vs. placebo (49.1%, P=.04).
Conclusions: The addition of orlistat to a conventional weight loss regimen significantly improved
oral glucose tolerance and diminished the rate of progression to the development of impaired glucose
tolerance and type 2 diabetes.
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"Following new dietary guidelines can save lives,"
Boggs W. Reuters Health, 1999; New York.
Six national health organizations joined forces to produce a common set of dietary guidelines that
offer protection against the major chronic diseases.
What you choose to eat has a major impact on your risk of developing major diseases such as cancer,
atherosclerosis, obesity and diabetes, according to Dr. Richard Deckelbaum of the American Heart
Association's Nutrition Committee.
The American Cancer Society, the American Dietetic Association, the American Academy of Pediatrics,
the National Institutes of Health, and the American Society for Clinical Nutrition also participated
in developing the guidelines.
These organizations, each of which had previously issued its own dietary guidelines, reviewed the
scientific basis for their recommendations and developed 1 unified set of guidelines that they
believe will reduce the risk of those 4 diseases, according to a report published in the July 27
issue of Circulation: Journal of the American Heart Association.
Under the new unified guidelines, a healthy diet will include less than 10% saturated fat and no more
than 30% total fat, as measured in calories.
Most of the daily intake, more than 55% of total calories, should come in the form of carbohydrates.
No more than 300 milligrams of cholesterol should be consumed each day, and daily salt intake should
be limited to less than 6 grams, or one teaspoon. Finally, total calories should be adjusted "to
achieve and maintain desirable weight," the authors suggest.
According to the guidelines, the simplest way of achieving these goals is:
- Eat a variety of foods.
- Choose most of what you eat from plant sources.
- Eat at least 5 servings of fruits and vegetables every day.
- Eat at least 6 servings of whole grain foods each day.
- Minimize the high-fat foods you eat, especially those from animal sources.
- Choose low-fat, low-cholesterol foods.
- Limit the amount of simple sugars in your diet.
Although the guidelines are designed to satisfy the needs of "the whole population (over) 2 years of
age," several groups raise special concerns. Problems such as obesity in children, undernourishment
among the elderly, and osteoporosis and iron deficiency in women require special intervention,
according to the report.
In an interview with Reuters Health, Deckelbaum offered this advice: "Get a copy of the Food Guide
Pyramid at your local library, paste it on your refrigerator, and follow it," he said. "By following
this handy, simple guide, you'll reduce your risk of heart disease, stroke, cancer, and diabetes."
"And when you're buying groceries, pay close attention to the nutritional labels," Deckelbaum added.
"Watch out for the total calories as well as the total fat. You want to keep both of them within the
guidelines."
SOURCE: Circulation: Journal of the American Heart Association 1999;100.
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