Orlistat

BMC Fam Pract. 2005 Jan 29;6(1):5.
Influence of intense multidisciplinary follow-up and orlistat on weight reduction in a primary care setting.
Feigenbaum A, Pasternak S, Zusk E, Sarid M, Vinker S.
Department of Family Medicine, Sackler School of Medicine, Tel Aviv University; Tel Aviv, Israel. vinker01@inter.net.il.

BACKGROUND: Obesity is the most common health problem in developed countries. Recently, several physicians' organizations have issued recommendations for treating obesity to family physicians, including instructions in nutrition, physical activity and medications. The aim of this study was to examine if effective weight-reducing treatment can be given by a family physician. It compares regular treatment with intensive treatment that include close follow-up and orlistat treatment. METHODS: The study was conducted in three primary care clinics. 225 patients were divided into three groups according to their choice. Group A received a personal diet with fortnightly meetings with the family physician and dietitian and orlistat treatment. Group B received a general diet, monthly meetings with the family physician only and orlistat treatment. Group C received a personal diet, monthly meetings with the dietitian only and no drug treatment. The primary endpoint was reduction of at least 5% of the initial weight during the study period. RESULTS: A greater percentage of patients in group A achieved their weight reduction goals than in other groups (51%, 13% and 9% in groups A, B and C, respectively, p < 0.001). There was a significant reduction in triglycerides in all groups, a significant reduction of low density lipids (LDL) in groups A and B and no significant difference in high density lipids (HDL) in any group. CONCLUSIONS: Significant weight reduction was obtained in a family physician setting. Further research is needed to evaluate if, by providing the family physician with the proper tools, similar success can be achieved in more clinics.

Int J Obes Relat Metab Disord. 2005 Mar 01;
Orlistat in responding obese type 2 diabetic patients: meta-analysis findings and cost-effectiveness as rationales for reimbursement in Sweden and Switzerland.
Ruof J, Golay A, Berne C, Collin C, Lentz J, Maetzel A.
[1] 1Health Services Research Unit, Division of Rheumatology, Center of Internal Medicine, Hannover Medical School, Hannover, Germany [2] 2Global Health Economics Department, Roche Pharmaceuticals, Basel, Switzerland.

OBJECTIVE:: The aim of this study is to review the clinical and economic rationale for the reimbursement of orlistat in responding obese patients with type 2 diabetes. METHODS:: Data from seven randomized controlled clinical trials of orlistat in overweight and obese patients with type 2 diabetes were pooled. A subgroup analysis involving patients who achieved a response (defined as a weight loss of >/=5% after 12 weeks of treatment) was conducted. The outcomes of the pooled analysis were then used to construct a Markov health economic model covering an 11-y period. The incidences of diabetes-related micro- and macrovascular complications were derived from the United Kingdom Prospective Diabetes Study. The effects of changes in body mass index, and the impact of micro- and macrovascular complications on utilities were derived from published sources. Publicly available cost data were used and are presented here in 2001 Euros. Discounting of 3% was applied. A probabilistic sensitivity analysis was conducted to examine the robustness of results. RESULTS:: A total of 1249 patients treated with orlistat and 1230 given placebo were eligible for the intent-to-treat analysis. At the end of the study period, 23% of orlistat patients achieved a weight reduction of >/=5%. These patients showed a mean decrease in HbA1C of 1.16%, a weight reduction of 8.6 kg, a reduction in total cholesterol of 5.3% and a reduction in systolic blood pressure of 5.2 mmHg. The base-case economic analysis revealed costs per quality-adjusted life year gained of \[euro]14 000 in Sweden and \[euro]13 600 in Switzerland. CONCLUSION:: The data presented here support the utilization and reimbursement of orlistat in overweight and obese diabetic patients who respond to the treatment.International Journal of Obesity advance online publication, 1 March 2005; doi:10.1038/sj.ijo.0802925.

Diabetes Care. 2004 Jan;27(1):155-61.
XENical in the Prevention of Diabetes in Obese Subjects (XENDOS) Study: A randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients.
Torgerson JS, Hauptman J, Boldrin MN, Sjostrom L.
Department of Body Composition and Metabolism, Sahlgrenska University Hospital, Goteborg, Sweden. Hoffmann-La Roche, Nutley, New Jersey.
OBJECTIVE:-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. RESEARCH DESIGN AND METHODS-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 >/==" BORDER="0">30 kg/m(2) 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. RESULTS:-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). CONCLUSIONS:-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 and or NGT.

Int J Obes Relat Metab Disord. 2003 Dec;27(12):1486-93.
Weight loss in obese Mexican Americans treated for 1-year with orlistat and lifestyle modification.
Carlos Poston WS, Reeves RS, Haddock CK, Stormer S, Balasubramanyam A, Satterwhite O, Taylor JE, Foreyt JP.
1Mid America Heart Institute and University of Missouri-Kansas City, Kansas City, MO, USA.
OBJECTIVE:: To evaluate the effectiveness of a culturally appropriate lifestyle intervention combined with orlistat in producing weight loss with obese Mexican-American women. SUBJECTS:: Mexican-American women (N=108), aged 21-65 y, with a body mass index (BMI) >/=27 kg/m(2) were randomized to 1 y of treatment with orlistat and a culturally tailored lifestyle modification intervention (OLM; n=56) or a wait-list control group (WLC; n=52). DESIGN:: A randomized, controlled, open-label 12-month study. Orlistat was dosed at 120 mg, three times per day. The OLM intervention included behavior modification, a low-fat (</=30% of total daily calories) diet, and moderate physical activity (>/=150 min/week). MEASUREMENT:: Primary outcomes included changes in body weight (kg), BMI, waist circumference, blood pressure, glucose, and lipids. RESULTS:: A total of 72 (37 OLM, 35 WLC) and 66 participants (32 OLM, 34 WLC) completed the 6- and 12-month follow-ups, respectively. Repeated-measures ANOVA demonstrated a significant time x treatment interaction (Wilks' lambda=12.61; P<0.001), indicating that OLM-treated patients achieved significant weight loss relative to the WLC group during the study (mean percentage weight loss+/-s.e.m.; -8.1%+/-1.2 vs -1.6%+/-0.7 at 6 months and -8.8%+/-1.5 vs -0.2%+/-1.0 at 12 months, respectively). OLM-treated patients also experienced significant reductions in waist circumference, low-density-lipoprotein, and total cholesterol. CONCLUSIONS:: This study demonstrates the effectiveness of an intervention combining orlistat and lifestyle modification with Mexican-American women, a population with substantial risk for obesity

Int J Obes Relat Metab Disord. 2003 Dec;27(12):1479-85.
Effects of a lipase inhibitor (Orlistat) on cholecystokinin and appetite in response to a high-fat meal.
Goedecke JH, Barsdorf M, Beglinger C, Levitt NS, Lambert EV.
1UCT/MRC Research Unit for Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town, South Africa.
OBJECTIVE:: To examine the short-term effects of a lipase inhibitor (Orlistat) on physiological and behavioural measures of appetite in response to a high-fat meal. DESIGN:: Randomised, single blind, placebo-controlled, crossover trial. SUBJECTS:: A total of 19 healthy nonobese male subjects. PROCEDURES:: After an overnight fast, subjects ingested a test meal of 2940 kJ (60% fat, 30% CHO, 10% protein) with Orlistat (120 mg) or a placebo, separated by 2 weeks. Appetite, as assessed by a standard line scale, and plasma cholecystokinin (CCK) concentrations were measured prior to and every hour after the test meal for 4 h. Thereafter, subjects ingested a quantified, but self-selected portion of a standardised lunch (15% protein, 37% fat and 45% CHO), before completing a final line scale questionnaire. RESULTS:: The CCK response to the test meal was negatively correlated with BMI in both the Orlistat and placebo trials (R=-0.69 and -0.65, P<0.01). Orlistat administration did not significantly alter the CCK response to the test meal (6.30+/-3.27 vs 7.36+/-3.94 pM min, for Orlistat and placebo, P=0.193). Similarly, the line scale measures of appetite and subsequent intake (520+/-205 vs 554+/-197 g, P=0.48) were not different between the trials. CONCLUSION:: Orlistat administration did not alter short-term physiological or behavioural measures of satiety in response to a high-fat meal in healthy, nonobese subjects. The CCK response to a test meal may be partly determined by BMI.International Journal of Obesity (2003) 27, 1479-1485.

J Hypertens. 2003 Nov;21(11):2159-2165.
Orlistat in hypertensive overweight/obese patients: results of a randomized clinical trial.
Bloch KV, Salles GF, Muxfeldt ES, Da Rocha Nogueira A.
Hypertension Program, Departments of Preventive Medicine and Internal Medicine, Medical School, Internal Medicine Unit, University Hospital Clementino Fraga Filho and Epidemiology Unit, University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
SUMMARY: OBJECTIVE To assess the effect of orlistat plus diet compared with diet alone in promoting weight loss and blood pressure reduction in hypertensive, overweight/obese patients.DESIGN A pragmatic randomized, controlled trial.SETTING Hypertension clinic of a university hospital.PATIENTS Hypertensive patients aged 18-75 years with a body mass index greater than 25 kg/m2.INTERVENTIONS Orlistat 360 mg/day combined with a hypocaloric diet (treatment group), or a calorie-restricted diet alone (control group).MAIN OUTCOME MEASURES Primary outcomes were reductions in weight and blood pressure. Secondary outcomes were decreases in lipid and glucose concentrations. A subgroup analysis of the main outcomes among diabetic and non-diabetic patients was also performed.RESULTS A total of 204 patients were included in the intention-to-treat analysis. After 12 weeks the orlistat group lost, on average, 3.7 kg and the control group lost 2.0 kg in weight (P < 0.001). Systolic (SBP) and diastolic (DBP) blood pressures decreased by 15.3 and 11.4 mmHg, respectively, in the group given orlistat plus a hypocaloric diet and by 11.6 and 5.2 mmHg, respectively, in the control group given the calorie-restricted diet alone (P = 0.25 and P = 0.0004, respectively). Fasting glucose (0.82 and 0.17 mmol/l, P = 0.01) and total cholesterol (0.85 and 0.56 mmol/l, P = 0.05) were reduced to a greater extent with orlistat than with diet alone. The mean reduction in triglycerides with orlistat plus the hypocaloric diet was 0.75 mmol/l and that in the control group was 0.30 mmol/l (P = 0.28); the increases in high-density lipoprotein cholesterol were 0.05 and 0.00 mmol/l, respectively, in the two groups (P = 0.17). Treatment improved blood pressure and glucose control in the individuals with diabetes, but not in those without diabetes.CONCLUSION In both groups there was a reduction in weight, blood pressure and metabolic parameters. The orlistat group performed better in reducing weight, DBP, glucose and cholesterol. Results show that even a small reduction in weight helps to control blood pressure and glucose. The cost-benefit of the use of orlistat should be evaluated for hypertensive obese patients.

Cochrane Database Syst Rev. 2003;4:CD004094.
Long-term pharmacotherapy for obesity and overweight.
Padwal R, Li S, Lau D.
Division of Clinical Pharmacology, Sunnybrook and Women's College Health Sciences Center, Room E2-42, 2075 Bayview Avenue, Toronto, Ontario, CANADA, M4N 3M5.
BACKGROUND: Worldwide prevalence rates of obesity and overweight are rising and safe and effective treatment strategies are urgently needed. A number of anti-obesity agents have been studied in short-term clinical trials, but long-term efficacy and safety need to be established. OBJECTIVES: To assess/compare the effects and safety of approved anti-obesity medications in clinical trials of at least one-year duration. SEARCH STRATEGY: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, the Current Science Meta-register of Controlled Trials, and reference lists of original studies and reviews were searched. Date of last search was December 2002. Drug manufacturers and two obesity experts were contacted in to detect unpublished trials. No language restrictions were imposed. SELECTION CRITERIA: Double-blind, randomised controlled weight loss and weight maintenance trials of approved anti-obesity agents that 1) enrolled adult overweight or obese patients, 2) included a placebo control group or compared two or more anti-obesity drugs 3) used an intention-to-treat analysis, and 4) had a minimum follow-up period of one year. Abstracts and pseudo-randomised trials were not included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed all potentially relevant citations for inclusion and methodological quality. The primary outcome measure was weight loss. MAIN RESULTS: Of the eight anti-obesity agents investigated, only orlistat and sibutramine trials met inclusion criteria. Eleven orlistat weight loss studies (four of which reported a second year weight maintenance phase) and five sibutramine studies (three weight loss and two weight maintenance trials) were included. Attrition rates averaged 33% during the weight loss phase of orlistat trials and 43% in sibutramine studies. All patients received lifestyle modification as a co-intervention. Compared to placebo, orlistat-treated patients lost 2.7 kg (95% CI: 2.3 kg to 3.1 kg) or 2.9% (95% CI: 2.3 % to 3.4%) more weight and patients on sibutramine experienced 4.3 kg (95% CI: 3.6 kg to 4.9 kg) or 4.6% (95% CI: 3.8% to 5.4%) greater weight loss. The number of patients achieving ten percent or greater weight loss was 12% (95% CI: 8% to 16%) higher with orlistat and 15% (95% CI: 4% to 27%) higher with sibutramine therapy. Weight loss maintenance results were similar. Orlistat caused gastrointestinal side effects and sibutramine was associated with small increases in blood pressure and pulse rate. REVIEWER'S CONCLUSIONS: Studies evaluating the long-term efficacy of anti-obesity agents are limited to orlistat and sibutramine. Both drugs appear modestly effective in promoting weight loss; however, interpretation is limited by high attrition rates. Longer and more methodologically rigorous studies of anti-obesity drugs that are powered to examine endpoints such as mortality and cardiovascular morbidity are required to fully evaluate any potential benefit of such agents.