Comparison of efficacy of sibutramine or orlistat versus their combination in obese women.

Sari R, Balci MK, Cakir M, Altunbas H, Karayalcin U.

Department of Internal Medicine, Division of Endocrinology and Metabolism, School of Medicine, Akdeniz University, Antalya, Turkey. drsari hotmail.com

OBJECTIVE: Sibutramine and orlistat are currently used for weight loss. We aimed to investigate the effect of orlistat and sibutramine combination therapy in treatment of obese women. SUBJECTS AND DESIGN: Study population consisted of 89 obese women who had a body mass index > or = 30 kg/m2, were normotensive, and had normal glucose tolerance. All patients were placed on a diet which contained fat approximately 30% of total calorie intake and the diet was designed to cause an energy deficit of approximately 2.51-3.56 megajoule/day. At the first month of diet (baseline), all patients were randomly divided into three therapy groups: Diet + Orlistat (group 1; n = 30 patients), Diet + Sibutramine (group 2; n = 29 patients), Diet + Orlistat + Sibutramine (group 3; n = 30 patients). Body weight, body fat distribution and serum lipid levels were evaluated baseline and after six months in all subjects. RESULTS: Mean weight loss was 5.5 +/- 4.9 kg (p = 0.024) in group 1, 10.1 +/- 3.6 kg (p < 0.001) in group 2, 10.8 +/- 6.6 kg (p < 0.001) in group 3 after the six months. Weight loss was significantly greater in group 2 (p = 0.003) and group 3 (p = 0.002) when compared with group 1. Percentage of mean weight loss was 5.5 +/- 3.1% in group 1, 10.2 +/- 4.8% in group 2, 10.6 +/- 5.7% in group 3. Percentage of weight loss was higher in group 2 (p = 0.01) and group 3 (p = 0.009) when compared with group 1. Weight loss and percentage of weight loss were not different between group 2 and group 3. CONCLUSION: These three regimens had different results on weight loss in obese women. Combination drug therapy and sibutramine therapy were both more effective than orlistat therapy alone. However, no significant difference was noted between combination drug therapy and sibutramine treatment groups.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15473126&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


What's the evidence that NICE guidance has been implemented? Results from a national evaluation using time series analysis, audit of patients' notes, and interviews.

Sheldon TA, Cullum N, Dawson D, Lankshear A, Lowson K, Watt I, West P, Wright D, Wright J.

Department of Health Sciences, University of York, York YO10 5DD. tas5 york.ac.uk

OBJECTIVES: To assess the extent and pattern of implementation of guidance issued by the National Institute for Clinical Excellence (NICE). DESIGN: Interrupted time series analysis, review of case notes, survey, and interviews. SETTING: Acute and primary care trusts in England and Wales. PARTICIPANTS: All primary care prescribing, hospital pharmacies; a random sample of 20 acute trusts, 17 mental health trusts, and 21 primary care trusts; and senior clinicians and managers from five acute trusts. MAIN OUTCOME MEASURES: Rates of prescribing and use of procedures and medical devices relative to evidence based guidance. RESULTS: 6308 usable patient audit forms were returned. Implementation of NICE guidance varied by trust and by topic. Prescribing of some taxanes for cancer (P < 0.002) and orlistat for obesity (P < 0.001) significantly increased in line with guidance. Prescribing of drugs for Alzheimer's disease and prophylactic extraction of wisdom teeth showed trends consistent with, but not obviously a consequence of, the guidance. Prescribing practice often did not accord with the details of the guidance. No change was apparent in the use of hearing aids, hip prostheses, implantable cardioverter defibrillators, laparoscopic hernia repair, and laparoscopic colorectal cancer surgery after NICE guidance had been issued. CONCLUSIONS: Implementation of NICE guidance has been variable. Guidance seems more likely to be adopted when there is strong professional support, a stable and convincing evidence base, and no increased or unfunded costs, in organisations that have established good systems for tracking guidance implementation and where the professionals involved are not isolated. Guidance needs to be clear and reflect the clinical context.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15514342&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


Prevention of type 2 diabetes mellitus through inhibition of the Renin-Angiotensin system.

Scheen AJ.

Division of Diabetes, Department of Medicine, Nutrition and Metabolic Disorders, CHU Sart Tilman, Liege, Belgium. Andre.Scheen chu.ulg.ac.be

Type 2 diabetes mellitus is becoming a major health problem associated with excess morbidity and mortality. As the prevalence of type 2 diabetes is rapidly increasing, prevention of the disease should be considered as a key objective in the near future. Besides lifestyle changes, various pharmacological treatments have proven their efficacy in placebo-controlled clinical trials, including antidiabetic drugs such as metformin, acarbose and troglitazone, or antiobesity agents such as orlistat. Arterial hypertension, a clinical entity in which insulin resistance is common, is strongly associated with type 2 diabetes and may precede the disease by several years. While antihypertensive agents such as diuretics or beta-adrenoceptor antagonists may worsen insulin resistance and impair glucose tolerance, newer antihypertensive agents exert neutral or even slightly positive metabolic effects. Numerous clinical trials have investigated the effects of ACE inhibitors or angiotensin II receptor antagonists (ARAs) on insulin sensitivity in hypertensive patients, with or without diabetes, with no consistent results. Almost half of the studies with ACE inhibitors in hypertensive nondiabetic individuals demonstrated a slight but significant increase in insulin sensitivity as assessed by insulin-stimulated glucose disposal during a euglycaemic hyperinsulinaemic clamp, while the other half failed to reveal any significant change. The effects of ARAs on insulin sensitivity are neutral in most studies. Mechanisms of improvement of glucose tolerance and insulin sensitivity through the inhibition of the renin-angiotensin system (RAS) are complex. They may include improvement of blood flow and microcirculation in skeletal muscles and, thereby, enhancement of insulin and glucose delivery to the insulin-sensitive tissues, facilitating insulin signalling at the cellular level and improvement of insulin secretion by the beta cells. Six recent large-scale clinical studies reported a remarkably consistent reduction in the incidence of type 2 diabetes in hypertensive patients treated with either ACE inhibitors or ARAs for 3-6 years, compared with a thiazide diuretic, beta-adrenoceptor antagonist, the calcium channel antagonist amlodipine or even placebo. The relative risk reduction averaged 14% (p = 0.034) in the CAPPP (Captopril Prevention Project) with captopril compared with a thiazide or beta1-adrenoceptor antagonist, 34% (p < 0.001) in the HOPE (Heart Outcomes Prevention Evaluation) study with ramipril compared with placebo, 30% (p < 0.001) in the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) with lisinopril compared with chlortalidone, 25% (p < 0.001) in the LIFE (Losartan Intervention For Endpoint reduction in hypertension study) with losartan compared with atenolol, and 25% (p = 0.09) in the SCOPE (Study on Cognition and Prognosis in the Elderly) with candesartan cilexetil compared with placebo, and 23% (p < 0.0001) in the VALUE (Valsartan Antihypertensive Long-term Use Evaluation) trial with valsartan compared with amlodipine. All these studies considered the development of diabetes as a secondary endpoint, except the HOPE trial where it was a post hoc analysis. These encouraging observations led to the initiation of two large, prospective, placebo-controlled randomised clinical trials whose primary outcome is the prevention of type 2 diabetes: the DREAM (Diabetes REduction Approaches with ramipril and rosiglitazone Medications) trial with the ACE inhibitor ramipril and the NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research) trial with the ARA valsartan. Finally, ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) will also investigate as a secondary endpoint whether it is possible to prevent the development of type 2 diabetes by blocking the RAS with either an ACE inhibitor or an ARA or a combination of both. Thus, the recent consistent observations of a 14-34% reduction of the development of diabetes in hypertensive patients receiving ACE inhibitors or ARAs are exciting. From a theoretical point of view, they emphasise that there are many aspects of the pathogenesis, prevention and treatment of type 2 diabetes that still need to be uncovered. From a practical point of view, they may offer a new strategy to reduce the ongoing epidemic and burden of type 2 diabetes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15516153&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


G protein polymorphisms do not predict weight loss and improvement of hypertension in severely obese patients.

Potoczna N, Wertli M, Steffen R, Ricklin T, Lentes KU, Horber FF.

Klinik Hirslanden, Zurich, Switzerland.

Both the gene encoding the alpha subunit of G stimulatory proteins (GNAS1) and the beta3 subunit gene (GNB3) of G proteins are associated with obesity and/or hypertension. Moreover, the TT/TC825 polymorphism of GNB3 predicts greater weight loss than the CC825 polymorphism in obese patients (mean body mass index, 35 kg/m2) undergoing a structured nonpharmacologic weight loss program. Gastric banding enforces a low-calorie diet by diminishing the need for volitional adherence. It is unknown whether these polymorphisms predict the variable weight loss in patients after bariatric surgery. Three hundred and four severely obese patients (mean +/- SEM age, 42 +/- 1 years; 245 women and 59 men; mean +/- SEM body mass index, 43.9 +/- 0.3 kg/m2) followed prospectively for at least 3 years after surgery were genotyped for the GNB3 C825T, G814A, and GNAS1 T393 polymorphisms. All analyses were performed blinded to the phenotypic characteristics of the study group. Frequencies of polymorphisms were comparable to those previously published. No polymorphism studied predicted 3-year weight loss or was associated with high blood pressure in severely obese patients after gastric banding. Multivariate analysis of potentially confounding factors such as reoperation rate or use of sibutramine or orlistat revealed similar results (P > 0.1). Regardless of the mechanism(s) involved for these discordant findings, GNB3 C825T, G814A, and GNAS1 T393C polymorphisms do not seem to be reliable predictors of long-term weight loss.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15531240&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


[Pharmacotherapy of obesity]

[Article in German]

Schusdziarra V, Erdmann J.

Klinik fur Ernahrungsmedizin der Technischen Universitat Munchen, Klinikum rechts der Isar.

While the intentional modification of eating habits remains the most important measure for losing weight, pharmacological support, in particular with regard to the long-term outcome, can be helpful. Catacholaminergic substances, such as diethylpropion and phenylpropanolamine are restricted by their side effects to short-term application only, and their use makes little sense. The serotoninergic substance sibutramine, which acts on the central nervous system to curb the appetite or enhance the feeling of saturation, and orlistat, which inhibits the assimilation of fat from the bowel, are approved for longer-term treatment of obesity, and lead to an additional loss of 3-5% of the patient's initial weight after one year of use. Thereafter, however, this benefit decreases. Further substances involving new, possibly combinable, approaches are currently under development.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15532736&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)