Jonathan Hauptman

Baylor University, Waco, Texas, United States

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Publications (21)

  • Article: Orlistat
    Jonathan Hauptman
    [Show abstract] [Hide abstract] ABSTRACT: Orlistat is a novel, noncentrally acting antiobesity agent that selectively inhibits gastro intestinal lipase activity, there by reducing the absorption of dietary fat by approximately one-third. In a series of 1- and 2-yr randomized, placebo-controlled trials of obese subjects, treatment with orlistat in combination with a mildly calorie-restricted diet consistently produced significantly greater mean weight loss than diet alone. More orlistat-treated subjects than placebo recipients achieved clinically meaningful weight reduction (≥5% or ≥10% of initial body weight) after 1 and 2 yr. Orlistat was also associated with a significant reduction in the regain of lost weight during long-term treatment. In addition, orlistat therapy resulted in significant improvements in several cardiovascular risk factors including serum total and low-density lipoprotein—cholesterol, serum insulin levels, systolic and diastolic blood pressure, and waist circumference. Furthermore, obese subjects with type 2 diabetes achieved a significantly greater decrease in body weight with orlistat compared with placebo, as well as significant improvements in HbA1c and fasting glucose levels. Among subjects with impaired glucose tolerance, orlistat compared with placebo reduced the proportion who developed type 2 diabetes. Conversely, orlistat increased the proportion of subjects who achieved a normalization of glucose tolerance. Orlistat acts locally in the gastrointestinal tract and is only minimally absorbed. In long-term clinical trials, orlistat was well tolerated by both diabetic and nondiabetic subjects.
    Article · Apr 2012 · Endocrine
  • James W Anderson · Susan M Schwartz · Jonathan Hauptman · [...] · Cecilia A Hale
    Article · Apr 2007 · Annals of Pharmacotherapy
  • James W Anderson · Susan M Schwartz · Jonathan Hauptman · [...] · Cecilia A Hale
    [Show abstract] [Hide abstract] ABSTRACT: Lifestyle measures are considered the first line of therapy for treating overweight individuals, but many are unable to achieve a meaningful weight loss. To determine the efficacy and safety of orlistat 60 mg, given 3 times daily, for weight loss in mildly to moderately overweight individuals. 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. 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. 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.
    Article · Oct 2006 · Annals of Pharmacotherapy
  • Source
    Jean-Pierre Chanoine · Sarah Hampl · Craig Jensen · [...] · Jonathan Hauptman
    [Show abstract] [Hide abstract] ABSTRACT: The prevalence of overweight and obesity in children and adolescents is increasing rapidly. In this population, behavioral therapy alone has had limited success in providing meaningful, sustained weight reduction, and pharmacological treatment has not been extensively studied. To determine the efficacy and safety of orlistat in weight management of adolescents. Multicenter, 54-week (August 2000-October 2002), randomized, double-blind study of 539 obese adolescents (aged 12-16 years; body mass index [BMI] >or=2 units above the 95th percentile) at 32 centers in the United States and Canada. A 120-mg dose of orlistat (n = 357) or placebo (n = 182) 3 times daily for 1 year, plus a mildly hypocaloric diet (30% fat calories), exercise, and behavioral therapy. Change in BMI; secondary measures included changes in waist and hip circumference, weight loss, lipid measurements, and glucose and insulin responses to oral glucose challenge. There was a decrease in BMI in both treatment groups up to week 12, thereafter stabilizing with orlistat but increasing beyond baseline with placebo. At the end of the study, BMI had decreased by 0.55 with orlistat but increased by 0.31 with placebo (P = .001). Compared with 15.7% of the placebo group, 26.5% of participants taking orlistat had a 5% or higher decrease in BMI (P = .005); 4.5% and 13.3%, respectively, had a 10% or higher decrease in BMI (P = .002). At study end, weight had increased 0.53 kg with orlistat and 3.14 kg with placebo (P<.001). Dual-energy x-ray absorptiometry showed that this difference was explained by changes in fat mass. Waist circumference decreased in the orlistat group but increased in the placebo group (-1.33 cm vs +0.12 cm; P<.05). Generally mild to moderate gastrointestinal tract adverse events occurred in 9% to 50% of the orlistat group and in 1% to 13% of the placebo group. In combination with diet, exercise, and behavioral modification, orlistat statistically significantly improved weight management in obese adolescents compared with placebo. The use of orlistat for 1 year in this adolescent population did not raise major safety issues although gastrointestinal adverse events were more common in the orlistat group.
    Full-text Article · Jun 2005 · JAMA The Journal of the American Medical Association
  • Jarl S Torgerson · Jonathan Hauptman · Mark N Boldrin · Lars Sjöström
    [Show abstract] [Hide abstract] ABSTRACT: It is well established that the risk of developing type 2 diabetes is closely linked to the presence and duration of overweight and obesity. A reduction in the incidence of type 2 diabetes with lifestyle changes has previously been demonstrated. We hypothesized that adding a weight-reducing agent to lifestyle changes may lead to an even greater decrease in body weight, and thus the incidence of type 2 diabetes, in obese patients. In a 4-year, double-blind, prospective study, we randomized 3,305 patients to lifestyle changes plus either orlistat 120 mg or placebo, three times daily. Participants had a BMI >/=30 kg/m2 and normal (79%) or impaired (21%) glucose tolerance (IGT). Primary endpoints were time to onset of type 2 diabetes and change in body weight. Analyses were by intention to treat. Of orlistat-treated patients, 52% completed treatment compared with 34% of placebo recipients (P < 0.0001). After 4 years' treatment, the cumulative incidence of diabetes was 9.0% with placebo and 6.2% with orlistat, corresponding to a risk reduction of 37.3% (P = 0.0032). Exploratory analyses indicated that the preventive effect was explained by the difference in subjects with IGT. Mean weight loss after 4 years was significantly greater with orlistat (5.8 vs. 3.0 kg with placebo; P < 0.001) and similar between orlistat recipients with impaired (5.7 kg) or normal glucose tolerance (NGT) (5.8 kg) at baseline. A second analysis in which the baseline weights of subjects who dropped out of the study was carried forward also demonstrated greater weight loss in the orlistat group (3.6 vs. 1.4 kg; P < 0.001). Compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinically representative obese population. Difference in diabetes incidence was detectable only in the IGT subgroup; weight loss was similar in subjects with IGT or NGT [correction].
    Article · Feb 2004 · Diabetes Care
  • Gerald Reaven · Karen Segal · Jonathan Hauptman · [...] · Charles Lucas
    [Show abstract] [Hide abstract] ABSTRACT: This study describes the changes in risk factors for coronary heart disease in obese persons with syndrome X after orlistat-assisted weight loss. Data were available for 1,700 patients who completed 52 weeks of weight loss; 128 were defined as having syndrome X by being in the quintile with the highest plasma triglyceride levels (>2.2 mM/L) and the lowest high-density lipoprotein cholesterol (HDL, <1.0 mM/L) concentrations. Initial characteristics of those with syndrome X were similar to the 119 subjects (non-syndrome X) in the lowest quintile of plasma triglyceride (<0.975 mM/L) and highest quintile of HDL cholesterol (>1.5 mM/L). Subjects were placed on a calorie-restricted diet, and randomized to receive orlistat or placebo. Initial values were higher in those with syndrome X for diastolic blood pressure (p = 0.03), plasma insulin (p = 0.0001), triglyceride (p = 0.0001) concentrations, and ratio of low-density lipoprotein cholesterol to HDL cholesterol (p = 0.0001), and were lower for HDL cholesterol (p = 0.001) concentrations. Weight loss was greater in both groups of orlistat-treated patients (p = 0.026); in those with syndrome X, it was associated with a significant reduction in plasma insulin (p = 0.019) and triglyceride (p = 0.0001) concentrations, an increase in HDL cholesterol concentration, and a decrease in low-density lipoprotein/HDL cholesterol ratio (p = 0.0001). There were no significant changes in plasma insulin, triglycerides, or HDL cholesterol concentration in the non-syndrome X group. In conclusion, weight loss attenuates coronary heart disease risk factors in obese persons with syndrome X, and the risk factor reduction is enhanced with administration of orlistat.
    Article · Apr 2001 · The American Journal of Cardiology
  • J Hauptman · C Lucas · M N Boldrin · [...] · K R Segal
    Article · Jan 2001 · Journal of Cardiopulmonary Rehabilitation
  • Gerald M. Reaven · Karen R. Segal · Jonathan Hauptman · [...] · Charles P. Lucas
    [Show abstract] [Hide abstract] ABSTRACT: All 214 subjects with elevated blood pressure (BP)(≥140/≥90 mmHg) were selected from the total pool of overweight or obese individuals who completed one year of treatment consisting of diet + placebo (P) or diet + orlistat (O). Compared to subjects with normal fasting insulin levels (<90 pm/L), hypertensive subjects with high fasting insulin levels (≥90 pm/L) had significantly higher (p<0.05) initial values for body weight, fasting glucose, LDL-cholesterol (LDL-C), LDL/HDL-C, triglycerides and systolic BP plus lower levels of HDL-C. After 1 year, no significant differences were observed between O and P in normal insulin subjects for changes in blood pressure, glucose, insulin or lipids despite greater weight loss with O vs P (-10.3±1.0% vs -6.4 ± 0.9%, p=0.0028). In high insulin subjects, the following changes were significantly greater for O than P: body weight (-9.3 ± 0.7% vs -5.2 ± 0.6%, p=0.0001), systolic BP (-17.6 ± 1.7 vs -12.6 ± 1.8 mmHg, p=0.035), diastolic BP (-10.6 ± 1.1 vs -8.5 ± 1.2 mmHg, p=0.022), insulin (-39 ± 5.8 vs -25 ± 7.5 pm/L, p=0.013), LDL-C (-0.49 ± 0.09 vs -0.18 ± 0.08 mm/L, p=0.035), or LDL/HDL-C (-0.44 ± 0.09 vs -0.09 ± 0.09, p=0.044). In conclusion, CV risk factors are more likely to be abnormal in high insulin hypertension, and orlistat was more effective than placebo in improving these risk factors.
    Article · Jan 2001
  • Jonathan Hauptman
    [Show abstract] [Hide abstract] ABSTRACT: Orlistat is a novel, noncentrally acting antiobesity agent that selectively inhibits gastrointestinal lipase activity, thereby reducing the absorption of dietary fat by approximately one-third. In a series of 1- and 2-yr randomized, placebo-controlled trials of obese subjects, treatment with orlistat in combination with a mildly calorie-restricted diet consistently produced significantly greater mean weight loss than diet alone. More orlistat-treated subjects than placebo recipients achieved clinically meaningful weight reduction (> or =5% or > or =10% of initial body weight) after 1 and 2 yr. Orlistat was also associated with a significant reduction in the regain of lost weight during long-term treatment. In addition, orlistat therapy resulted in significant improvements in several cardiovascular risk factors including serum total and low-density lipoprotein-cholesterol, serum insulin levels, systolic and diastolic blood pressure, and waist circumference. Furthermore, obese subjects with type 2 diabetes achieved a significantly greater decrease in body weight with orlistat compared with placebo, as well as significant improvements in HbA1c and fasting glucose levels. Among subjects with impaired glucose tolerance, orlistat compared with placebo reduced the proportion who developed type 2 diabetes. Conversely, orlistat increased the proportion of subjects who achieved a normalization of glucose tolerance. Orlistat acts locally in the gastrointestinal tract and is only minimally absorbed. In long-term clinical trials, orlistat was well tolerated by both diabetic and nondiabetic subjects.
    Article · Oct 2000 · Endocrine
  • Karen R Segal · Charles Lucas · Jonathan Hauptman · Priscilla Hollander
    Article · Sep 2000 · Diabetes Research and Clinical Practice
  • KR Segal · P Hollander · C Lucas · [...] · J Hauptman
    Article · Aug 2000 · Diabetologia
  • Steven B. Heymsfield · Karen R. Segal · Jonathan Hauptman · [...] · Lars Sjöström
    [Show abstract] [Hide abstract] ABSTRACT: 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. To test the hypothesis that orlistat combined with dietary intervention improves glucose tolerance status and prevents worsening of diabetes status more effectively than placebo. 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. 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. 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<.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). 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.
    Article · May 2000 · Archives of Internal Medicine
  • J Hauptman · C. P. Lucas · M N Boldrin · [...] · K R Segal
    [Show abstract] [Hide abstract] ABSTRACT: To evaluate the long-term efficacy and tolerability within primary care settings of orlistat, a gastrointestinal lipase inhibitor, for the treatment of obesity. Randomized, double-blind, placebo-controlled, multicenter study. A group of 796 obese patients (body mass index, 30-44 kg/m2), treated with placebo 3 times a day (TID), 60 mg of orlistat TID, or 120 mg of orlistat TID, in conjunction with a reduced-energy diet for the first year and a weight-maintenance diet during the second year. Seventeen primary care centers in the United States. Changes in body weight and obesity-related disease risk factors. Patients treated with orlistat lost significantly more weight (7.08 +/- 0.54 and 7.94 +/- 0.57 kg for the 60-mg and 120-mg orlistat groups, respectively) than those treated with placebo (4.14 +/- 0.56 kg) in year 1 (P<.001) and sustained more of this weight loss during year 2 (P<.001). More patients treated with orlistat lost 5% or more of their initial weight in year 1 (48.8% and 50.5% of patients in the 60-mg and 120-mg groups, respectively) compared with placebo (30.7%; P<.001), and approximately 34% of patients in the orlistat groups sustained weight loss of 5% or greater over 2 years compared with 24% in the placebo group (P<.001). Orlistat produced greater improvements than placebo in serum lipid levels and blood pressure and was well tolerated, although treatment resulted in a higher incidence of gastrointestinal events. This long-term study indicates that orlistat is an effective adjunct to dietary intervention in the treatment of obesity in primary care settings.
    Article · Feb 2000 · Archives of Family Medicine
  • C.P. Lucas · K.R. Segal · J. Hauptman
    [Show abstract] [Hide abstract] ABSTRACT: One out of four American women is clinically obese, and hence at greater risk for problems like heart disease, diabetes, menstrual irregularities, and polycystic ovary syndrome. Combining diet therapy and orlistat - a novel agent that reduces the absorption of dietary fat by 30%-may help control this national epidemic.
    Article · Jan 2000
  • KR Segal · S Heymsfield · J Hauptman · [...] · NJ Nutley
    Article · Aug 1999 · Diabetologia
  • Charles Lucas · Jonathan Hauptman · Hassan Amirikia · [...] · Mark Boldrin
    Article · Apr 1999 · Obstetrics and Gynecology
  • J. Hauptman · J. Dallas · G. Nichols · K. R. Segal
    Article · Apr 1999 · American Journal of Hypertension
  • M H Davidson · J Hauptman · M DiGirolamo · [...] · S B Heymsfield
    [Show abstract] [Hide abstract] ABSTRACT: 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.
    Article · Feb 1999 · JAMA The Journal of the American Medical Association
  • Source
    Michael H. Davidson · Jonathan Hauptman · Mario DiGirolamo · [...] · Steven B. Heymsfield
    [Show abstract] [Hide abstract] ABSTRACT: Context Orlistat, a gastrointestinal lipase inhibitor that reduces dietary fat absorption by approximately 30%, may promote weight loss and reduce cardiovascular risk factors.Objective 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.Design Randomized, double-blind, placebo-controlled study conducted from October 1992 to October 1995.Setting and Participants 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.Intervention 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.Main Outcome Measures Body weight change and changes in blood pressure and serum lipid, glucose, and insulin levels.Results 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.Conclusions Two-year treatment with orlistat plus diet significantly promotes weight loss, lessens weight regain, and improves some obesity-related disease risk factors. Figures in this Article Obesity, which affects an increasing number of Americans,1 poses a therapeutic challenge to the clinician. Conventional nonpharmacological interventions based on diet and exercise have limited long-term success in producing sustained weight loss.2- 3 Obesity induces multiple metabolic abnormalities that contribute to the pathogenesis of diabetes mellitus and cardiovascular disease4- 5 and is associated with increased morbidity and mortality risk.6- 7 A need therefore exists for new and effective therapeutic tools. A potentially promising approach is induction of negative energy balance and weight loss by drug-mediated inhibition of nutrient absorption. Orlistat (Xenical, Hoffman La Roche Inc, Nutley, NJ), a minimally absorbable (<1%) agent that inhibits activity of pancreatic and gastric lipases, blocks gastrointestinal uptake of approximately 30% of ingested fat.8 Assuming incomplete energy compensation, the treated subject consuming an average American diet should gradually lose weight and maintain weight loss. The primary aim of this investigation was to test this hypothesis in a large-scale, 2-year, randomized, double-blind, placebo-controlled study. While weight loss is an important end point in obesity treatment, the primary concern in medical management of obesity is morbidity and mortality risk reduction by improving underlying cardiovascular and metabolic risk factors: high blood pressure, atherogenic dyslipidemia, and insulin resistance. A widely held view, which has not been subjected to rigorous critical evaluation in large-scale prospective studies, is that modest (approximately 5%-10%) intentional weight loss is associated with significant improvements in obesity-related cardiovascular and metabolic abnormalities.9- 10 A secondary aim of this study was to examine the effectiveness of 2-year orlistat administration in improving blood pressure, lipid, and carbohydrate metabolism abnormalities, which often occur in obesity.
    Full-text Article · Jan 1999 · JAMA The Journal of the American Medical Association
  • PA Hollander · S C Elbein · I B Hirsch · [...] · J Hauptman
    [Show abstract] [Hide abstract] ABSTRACT: 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. In a multicenter 57-week randomized double-blind placebo-controlled study, 120 mg 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. 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 > or = 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-to-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. 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.
    Article · Aug 1998 · Diabetes Care