Pharmacotherapy and surgery in the treatment of obesity: evaluating risks and benefits.

Sum CF.

Diabetes Center, Alexandria Hospital, Singapore.

The prevalence of obesity is rising in many parts of the world. In Singapore, the 1998 National Health Survey reported the crude prevalence of obesity (BMI >/= 30 kg/m2) amongst adults as 6%. Together with the increase in obesity in certain sectors of the Singapore population (Malay community) there has been a parallel increase in the prevalence of impaired glucose tolerance. If left unchecked, this epidemic of obesity and its comorbidities will lead to reduced quality of life amongst its sufferers as well as an increase in consumption of healthcare resources. Although strategies at the community level are important to check this epidemic, when managing the individual patient with clinically significant obesity and its comorbidities, adjunctive pharmacotherapy and surgical measures are sometimes required besides lifestyle measures and behaviour therapy. Since these therapeutic measures are not without risks, a customized approach utilizing risk-benefit evaluation is appro-priate. Pharmacotherapy for the management of obesity has had a chequered history Prom the early disrepute brought about by patient dependence when using amphetamine-like agents, it improved in standing when obesity became more widely accepted as a chronic disorder requiring chronic adjunctive pharmacotherapy. However, the adverse cardiovascular effects reported with the 'fen-phen' combination again reduced enthusiasm for long-term pharmacotherapy. Subsequently, the availability of intestinal lipase inhibitor, orlistat, followed by the mixed noradrenergic-serotoninergic re-uptake inhibitor, sibutramine, gave fresh impetus to this therapeutic area. Both agents were made available for clinical use only after published clinical trial experience of one to two years duration. The difficulties encountered in management of patients with marked obesity have prompted adjunctive surgical initiatives. Follow-up reports from the Swedish Obese Subjects study which began in 1987, have provided valuable data on the effect of surgery on obesity as well as its comorbidities. At the same time, technological advances in surgery have facilitated the widespread use of less invasive approaches to bariatric surgery. It is hoped that with these technological advances, this group of patients will be able to enjoy the benefits of surgery without being exposed to excessive surgical risks.

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xenical (orlistat)


Impact of carbohydrate and fat intake on weight-reducing efficacy of orlistat.

Ullrich A, Erdmann J, Margraf J, Schusdziarra V.

Tiefenthal Hospital, Saarbrucken, Germany.

BACKGROUND: Orlistat treatment of obesity results in a poor long-term weight loss (< 5%) in about 30% of patients. AIM: Total energy and macronutrient intake were examined to assess the effect of a change in eating habits on weight loss. METHODS: Sixty-two patients consumed a hypocaloric diet, together with orlistat (3 x 120 mg/day), for 72 weeks, with a maximal fat allowance of 30% of the energy intake. At regular intervals, food diaries were recorded. RESULTS: Fifty-six patients completed the study and lost 8.5 +/- 0.88 kg (P < 0.001). Energy intake was approximately 1500 kcal/day during the entire study period. In three sub-groups established according to weight loss (1, < 5%; 2, > 5% and < 10%; 3, > 10%), fat intake was within the recommended range in all groups during the first 6 months, but thereafter only in group 3. All groups increased their carbohydrate consumption, with the greatest increase in group 1, which could account for the rapid regain of initially lost body weight in this group. CONCLUSION: At the beginning of a weight management programme in conjunction with orlistat, a low fat intake is advised for an efficient reduction in body weight. Subsequently, in patients with poor long-term weight loss, dietary recommendations must also consider carbohydrate restriction to ensure an adequate hypocaloric diet.

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Economic evaluation of orlistat in overweight and obese patients with type 2 diabetes mellitus.

Maetzel A, Ruof J, Covington M, Wolf A.

University Health Network Research Institute, University of Toronto, Toronto, Ontario, Canada. maetzel uhnres.utoronto.ca

OBJECTIVE: To estimate the economic value of pharmacological treatment of type 2 diabetes mellitus in overweight and obese patients using orlistat in addition to standard diabetes therapy (i.e., a sulphonlyurea, metformin or insulin) and weight management strategies as compared with standard diabetes therapy and weight management strategies alone in a US-based healthcare setting. The perspective of the study was from the viewpoint of a US healthcare provider. DESIGN AND SETTING: Markov state transition model simulating diabetes-related complications and mortality for a period of 11 years. Patients were modelled to continue orlistat therapy for a 52-week period, assuming a 3-year period of weight regain where after 3 years bodyweight would match that of the placebo group. The impact of orlistat on glycosylated haemoglobin (HbA(1c)) values was evaluated directly using data from four randomised, placebo-controlled, 1-year trials of orlistat in overweight or obese adults with type 2 diabetes who also received standard diabetes pharmacotherapy and intensive lifestyle modification. Incidence rates of micro- and macrovascular complications associated with type 2 diabetes and the estimated relative reduction in incidence rates associated with a decrease in mean updated HbA(1C) values were derived from the United Kingdom Prospective Diabetes Study (UKPDS) estimates for a reference population of male patients, 52 years of age. US cost estimates were derived from published sources and presented in 2001 US dollars. Discounting of 3% was applied. Probabilistic sensitivity analysis was applied to evaluate the robustness of the results of the persistence of the effect of orlistat after treatment. MAIN OUTCOME MEASURES: Average costs and event-free life-years gained during the 11-year period expressed as the incremental costs divided by the incremental gain in life expectancy. RESULTS: Treatment with orlistat, 120 mg three times daily, increased event-free life expectancy by 0.13 years over an 11-year period. Average treatment costs were estimated to be 19,987 US dollars in the orlistat group compared with 18,865 US dollars in the group that received diabetes medication and weight management alone. This translated into a cost-effectiveness ratio of 8327 US dollars per event-free life-year gained. CONCLUSION: Adding orlistat as a pharmacological treatment to conventional diabetes and weight management approaches seems to be a cost-effective treatment option for overweight and obese patients with type 2 diabetes.

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xenical (orlistat)


Importance of lipolysis in oral cavity for orosensory detection of fat.

Kawai T, Fushiki T.

Laboratory of Nutrition Chemistry, Department of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Japan.

Lingual lipase is usually secreted from von Ebner's glands, although there is great variation between species. Lingual lipase is thought to be an auxiliary enzyme for fat digestion and absorption in mammals; however, the reason for lipolysis in the oral cavity is not known. We focused on the gustatory sense and investigated the significance of lingual lipase in the perception of a fat taste by using orlistat, a potent lipase inhibitor. Five-minute two-bottle preference tests demonstrated that the addition of orlistat diminished the preference for triacylglycerides but not for free fatty acids. Radioactive triolein applied on rats' circumvallate papilla revealed that lingual lipase was released continuously to generate significant amounts of fatty acids and other lipolytic products within 1-5 s, which was enough time to taste fat. These findings suggest that lingual lipase is released to perceive the taste of triacylglycerides and to find nutritive lipids in food.

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xenical (orlistat)


National trends in antiobesity medication use.

Stafford RS, Radley DC.

Stanford Center for Research in Disease Prevention, 1000 Welch Road, Palo Alto, CA 94304, USA. rstafford stanford.edu

BACKGROUND: The use of medications to treat obesity remains controversial. Our goal was to assess national trends in antiobesity medication use with a focus on patterns surrounding the 1997 removal of antiobesity drugs from the market. METHODS: Using a serial cross-sectional study design, we analyzed a nationally representative sample of US office-based physician visits from 1991 to 2002. Data come from the IMS HEALTH National Disease and Therapeutic Index. These data include a sample of 13 452 patient visits for which a diagnosis of clinical obesity was made, with annual visits ranging from 666 in 1994 to 1854 in 1996. The unit of analysis is the patient visit, while the primary outcome measures are the annual and quarterly number of antiobesity drug mentions for clinically obese patients. RESULTS: At its peak in the second quarter of 1997, 2.5 million Americans were taking antiobesity medications, a 4-fold increase over the prior 2 years. Although antiobesity medication use diminished following the market exit of fenfluramine hydrochloride and dexfenfluramine hydrochloride, current levels of use remain above those in the early 1990s. Phentermine has consistently been the most common antiobesity medication. In 2002, an annualized 1.2 million mentions of phentermine use were noted (31% of drug-treated obese patients). Newly released medications, orlistat (0.6 million) and sibutramine hydrochloride (0.4 million), were used less often. Most antiobesity medication use occurs in patients without other reported medical conditions. CONCLUSIONS: Use of antiobesity medications increased rapidly with public and professional interest in fenfluramine-phentermine (fen-phen) combination therapy. Despite reports of adverse outcomes associated with fenfluramine agents (fen-phen and dexfenfluramine), the use of these medication therapies did not diminish until soon before their removal from the market in 1997.

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xenical (orlistat)