Nutraceutical resources for diabetes prevention--an update.

McCarty MF.

NutriGuard Research, 1051 Hermes Avenue, Encinitas, CA 92024, USA. mccarty pantox.com

There is considerable need for safe agents that can reduce risk for diabetes in at-risk subjects. Although certain drugs--including metformin, acarbose, and orlistat--have shown diabetes-preventive activity in large randomized studies, nutraceuticals have potential in this regard as well. Natural agents which slow carbohydrate absorption may mimic the protective effect of acarbose; these include: soluble fiber--most notably glucomannan; chlorogenic acid--likely responsible for reduction in diabetes risk associated with heavy coffee intake; and legume-derived alpha-amylase inhibitors. There does not appear to be a natural lipase inhibitor functionally equivalent to orlistat, although there are poorly documented claims for Cassia nomame extracts. Metformin's efficacy reflects activation of AMP-activated kinase; there is preliminary evidence that certain compounds in barley malt have similar activity, without the side effects associated with metformin. In supraphysiological concentrations, biotin directly activates soluble guanylate cyclase; this implies that, at some sufficient intake, biotin should exert effects on beta cells, the liver, and skeletal muscle that favor good glucose tolerance and maintenance of effective beta cell function. Good magnesium status is associated with reduced diabetes risk and superior insulin sensitivity in recent epidemiology; ample intakes of chromium picolinate appear to promote insulin sensitivity in many individuals and improve glycemic control in some diabetics; calcium/vitamin D may help preserve insulin sensitivity by preventing secondary hyperparathyroidism. Although conjugated linoleic acid--like thiazolidinediones, a PPAR-gamma agonist--has not aided insulin sensitivity in clinical trials, the natural rexinoid phytanic acid exerts thiazolidinedione-like effect in animals and cell cultures, and merits clinical examination. Other natural agents with the potential to treat and possibly prevent diabetes include extracts of bitter melon and of cinnamon. Nutraceuticals featuring meaningful doses of combinations of these agents would likely have substantial diabetes-preventive efficacy, and presumably could be marketed legally as aids to good glucose tolerance and insulin sensitivity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15533633&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


Orlistat is as beneficial as metformin in the treatment of polycystic ovarian syndrome.

Jayagopal V, Kilpatrick ES, Holding S, Jennings PE, Atkin SL.

Department of Medicine, University of Hull, Michael White Centre for Diabetes and Endocrinology, Hull Royal Infirmary, Hull HU3 2RW, UK. V.Jayagopal hull.ac.uk

The objective of this study was to evaluate and compare the effect of treatment with orlistat vs. metformin on the hormonal and biochemical features of patients with polycystic ovarian syndrome (PCOS). Twenty-one Caucasian women with PCOS [mean (+/-SEM) age 27 +/- 0.9 yr and body mass index 36.7 +/- 3.3 kg/m(2)] participated in this prospective, randomized, open-labeled study. All subjects had an 8-wk run-in period of dietary modification and then randomized to receive either metformin (500 mg three times daily) or orlistat (120 mg three times daily) for 3 months. Weight, blood pressure, and fasting blood samples were taken at screening, randomization, and on completion. Insulin resistance (IR) was calculated using the homeostasis model of assessment (HOMA)-IR method [HOMA-IR = (insulin x glucose)/22.5]. The results are expressed as mean +/- SEM. When compared with baseline, treatment with both orlistat [93.5 +/- 11.5 ng/dl (3.24 +/- 0.4 nmol/liter) vs. 114.5 +/- 11.5 ng/dl (3.97 +/- 0.4 nmol/liter), P = 0.039] and metformin [97.2 +/- 11.5 ng/dl (3.37 +/- 0.4 nmol/liter) vs. 120.0 +/- 8.7 ng/dl (4.16 +/- 0.3 nmol/liter), P = 0.048] produced a significant reduction in total testosterone. Treatment with orlistat produced a 4.69% reduction in weight (99.0 +/- 6.0 vs. 94.6 +/- 6.1 kg, P = 0.002), and this reduction was more significant than the reduction produced by metformin (4.69 vs. 1.02%, P = 0.006). There was no significant reduction seen after either treatment group for fasting insulin, HOMA-IR, SHBG, or any of the lipid parameters studied. In this study, orlistat produced a significant reduction in weight and total testosterone. The reduction in total testosterone was similar to that seen after treatment with metformin. Therefore, orlistat may prove to be a useful adjunct in the treatment of PCOS.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15536162&dopt=Abstract orlistat Xenical online refs
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National institute for clinical excellence (NICE) guidance for anti-obesity medication: is it being followed?

Hayton B.

St Mary's Hospital, Greenhill Road, Leeds LS12 3QE, UK Barbara.Hayton eastleeds-pct.nhs.uk.

Background: Anti-obesity medication is being used increasingly by some general practitioners (GP) for obesity management (Lawrence, 2002). The aim of this audit was to identify whether the anti-obesity medication prescribed by GPs was in accordance with the NICE guidance (NICE, 2001a,b). Method: The medical notes and electronic patient records of 154 patients prescribed either orlistat or sibutramine between September 2002 and April 2003, were examined. Information about patients' weight, previous weight loss, previous dietary and physical activity advice, behaviour modification, time on medication, weight loss achieved and blood pressure were recorded and comparisons made with the NICE guidance. Results: NICE guidanceOrlistat (n = 103)Sibutramine (n = 51)Only for individuals who have lost at least 2.5 kg in the preceding month20% achieved this weight loss56% attempted to lose weightBMI calculated66% calculated 71% calculatedDietary advice given 80% received advice49% received advicePhysical activity discussed36% physical activity discussed26% physical activity discussedBehavioural modification10% documented0% documentedWeight loss after starting drug 4 weeksNone required by NICE22% lost at least 2 kg weight 3 months17% patients lost >5% of initial body weight16% patients lost >5% of initial body weight 6 months3% lost >10% of initial body weight8% lost >10% initial body weightBlood pressure /pulse rate monitoringNone required74% BP initially checked; 20% BP >145/90 mm Hg; 9% pulse rate checkedNo more than 12 months on medication8% patients prescribed for >12 months4% patients prescribed for >12 monthsBMI, body mass index; BP, blood pressure. Conclusion: The results show that the majority of patients prescribed with orlistat and sibutramine are not treated in accordance with the NICE guidance. The recommendation is that GPs are given further training about the optimum treatment associated with the prescription of anti-obesity medication. References: Lawrence, G. (2002) Prescribing Advisor. Personal communication. NICE (2001a) NHS National Institute for Clinical ExcellenceGuidance. Technology Appraisal Guidance No 22. Guidance on the use of orlistat for the treatment of obesity. NICE (2001b) NHS National Institute for Clinical Excellence Guidance. Technology Appraisal Guidance No 31. Guidance on the use of sibutramine for the treatment of obesity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15546437&dopt=Abstract orlistat Xenical online refs
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Pharmacologic prevention or delay of type 2 diabetes mellitus.

Anderson DC Jr.

Southwest Georgia Pharmacy Program, Department of Clinical and Administrative Pharmacy, College of Pharmacy, University of Georgia, Athens, GA, USA. danderso mail.rx.uga.edu

OBJECTIVE: To evaluate the current data on pharmacologic interventions intended to prevent or delay the onset of type 2 diabetes mellitus. DATA SOURCES: Searches of MEDLINE (1966-July 2002) and an extensive manual review of journals were performed using the key search terms diabetes mellitus, metformin, acarbose, troglitazone, orlistat, nateglinide, risk reduction, and prevention. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated, and all information deemed relevant was included for this review. Randomized controlled trials and meta-analyses were included if the primary outcome measure was prevention of diabetes and/or change in the rate of progression to diabetes. DATA SYNTHESIS: Type 2 diabetes mellitus is a growing epidemic. Major risk factors include obesity, impaired glucose tolerance, and impaired fasting glucose. Complications of diabetes result in significant morbidity and mortality and are a substantial public health issue. Four randomized, blinded, controlled trials have assessed the efficacy of different medications, including metformin, troglitazone, acarbose, and orlistat, at decreasing the risk of progression to diabetes in patients at risk for developing diabetes. All of these agents decreased the risk of progression to diabetes. CONCLUSIONS: Metformin, troglitazone, acarbose, and orlistat have been shown to decrease the risk of progression to diabetes in patients at risk for developing diabetes. Other questions that address issues such as identifying target populations, cost-effectiveness, and screening strategies must be answered to more fully define the place of pharmacologic therapy to prevent or delay diabetes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15562143&dopt=Abstract orlistat Xenical online refs
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Orlistat: a review of its use in the management of patients with obesity.

Curran MP, Scott LJ.

Adis International Limited, Auckland, New Zealand. demail adis.co.nz

Orlistat is an inhibitor of gastrointestinal lipases and, therefore, prevents the absorption of dietary fat. This agent reduces weight in obese adults and adolescents with or without comorbidities (including type 2 diabetes mellitus, hypercholesterolaemia, hypertension, metabolic syndrome) who received up to 4 years of therapy in conjunction with a hypocaloric diet. In obese patients, orlistat in combination with a hypocaloric diet improved metabolic risk factors and reduced the risk of developing type 2 diabetes. Furthermore, this agent was cost effective in patients with obesity, particularly those with type 2 diabetes. Orlistat is generally well tolerated, with gastrointestinal adverse events being most commonly reported. Orlistat, in addition to lifestyle and dietary intervention, is thus an attractive option for the treatment of patients with obesity, especially those with associated comorbidities or at risk of developing type 2 diabetes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15563254&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)