CONCLUSIONS: Sibutramine is effective in promoting weight loss. Weight loss with sibutramine is associated with both positive and negative changes in cardiovascular and metabolic risk factors. There is insufficient evidence to accurately determine the long-term risk-benefit profile for sibutramine.

5. Screening and interventions for obesity in adults: summary of the evidence for the U.S. Preventive Services Task Force.

Ann Intern Med. 2003 Dec 2;139(11):933-49.

Comment in: Ann Intern Med. 2003 Dec 2;139(11):I57.

McTigue KM, Harris R, Hemphill B, Lux L, Sutton S, Bunton AJ, Lohr KN. University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

BACKGROUND: Obesity poses a considerable and growing health burden. This review examines evidence for screening and treating obesity in adults.

DATA SOURCES: MEDLINE and Cochrane Library (January 1994 through February 2003).

STUDY SELECTION: Systematic reviews; randomized, controlled trials; and observational studies of obesity's health outcomes or efficacy of obesity treatment.

DATA EXTRACTION: Two reviewers independently abstracted data on study design, sample, sample size, treatment, outcomes, and quality.

DATA SYNTHESIS: No trials evaluated mass screening for obesity, so the authors evaluated indirect evidence for efficacy. Pharmacotherapy or counseling interventions produced modest (generally 3 to 5 kg) weight loss over at least 6 or 12 months, respectively. Counseling was most effective when intensive and combined with behavioral therapy. Maintenance strategies helped retain weight loss. Selected surgical patients lost substantial weight (10 to 159 kg over 1 to 5 years). Weight reduction improved blood pressure, lipid levels, and glucose metabolism and decreased diabetes incidence. The internal validity of the treatment trials was fair to good, and external validity was limited by the minimal ethnic or gender diversity of volunteer participants. No data evaluated counseling harms. Primary adverse drug effects included hypertension with sibutramine (mean increase, 0 mm Hg to 3.5 mm Hg) and gastrointestinal distress with orlistat (1% to 37% of patients). Fewer than 1% (pooled samples) of surgical patients died; up to 25% needed surgery again over 5 years.

CONCLUSIONS: Counseling and pharmacotherapy can promote modest sustained weight loss, improving clinical outcomes. Pharmacotherapy appears safe in the short term; long-term safety has not been as strongly established. In selected patients, surgery promotes large amounts of weight loss with rare but sometimes severe complications.

6. What interventions should we add to weight reducing diets in adults with obesity? A systematic review of randomized controlled trials of adding drug therapy, exercise, behaviour therapy or combinations of these interventions.

J Hum Nutr Diet. 2004 Aug;17(4):293-316.

Avenell A, Brown TJ, McGee MA, Campbell MK, Grant AM, Broom J, Jung RT, Smith WC. Health Services Research Unit, University of Aberdeen, Foresterhill, Aberdeen, UK.

Background

Evidence is needed for the effectiveness of interventions given with reducing diets for obese adults: drug therapy, exercise, or behaviour therapy.

Methods

We systematically reviewed randomized controlled trials in any language. We searched 13 databases and handsearched journals. Trials lasted 1 year or more. One investigator extracted data and a second checked data extraction. Trial quality was assessed.

Results

Adding orlistat to diet was associated with weight change for up to 24 months (-3.26 kg, 95% CI, -4.15 to -2.37 kg), and statistically significant beneficial changes were found for total and LDL cholesterol, blood pressure and glycaemic control. Adding sibutramine to diet was associated with a 12 month weight change of -4.18 kg (95% CI, -5.14 to -3.21 kg), and statistically significant beneficial effects on high density lipoprotein cholesterol (HDL) and triglycerides (TGs), but an increase in diastolic blood pressure. Adding exercise to diet, or to diet and behaviour therapy, was associated with improved weight loss for up to 36 months and improvements in HDL, TGs and blood pressure. Adding behaviour therapy to diet, or to diet and sibutramine together, was associated with improved weight loss for up to 18 months. Adding drugs, exercise or behaviour therapy to dietary advice was each associated with similar weight change.

Conclusions

Adding orlistat, sibutramine, exercise, or behaviour modification to dietary advice can improve long-term weight loss.

7. Weight loss in obese diabetic and non-diabetic individuals and long-term diabetes outcomes--a systematic review.

Diabetes Obes Metab. 2004 Mar;6(2):85-94.

Aucott L, Poobalan A, Smith WC, Avenell A, Jung R, Broom J, Grant AM. Department of Public Health, University of Aberdeen, Aberdeen, UK. L.aucott@abdn.ac.uk

The aim was to review the evidence for the long-term effects of weight loss on diabetes outcomes in obese people or for those at risk of developing type 2 diabetes. Current evidence is mostly based on short-term studies.

This is a systematic review of long-term outcomes of weight loss in studies published between 1966 and 2001. Eleven long-term studies with a follow up of more than 2 years were included. Results show that those with diabetes who lost weight intentionally significantly reduced their mortality risks by 25%.

Additionally, weight loss of 9-13 kg was most protective. Patients with the risk of developing diabetes due to either family history of diabetes or impaired glucose tolerance, saw a reduction in this risk. Those with large weight losses achievable with surgical interventions reduced their risk by at least 63%. Metabolic handling of glucose improved in 80% of those already with type 2 diabetes who lost weight. Based on one large study, intentional weight loss in obese patients appears to have a beneficial effect on mortality risk for those with type 2 diabetes. Clearly, further studies are needed to endorse this.

The risk of developing diabetes being reduced by weight loss was shown in seven studies. However, the results were from studies with different analytical adjustments and outcome indices, making it difficult to make direct comparisons and should be viewed with caution.

More long-term prospective studies need to be conducted with commitment to improving the methodological quality and standardization, in order to accurately assess the long-term effects of weight loss for obese diabetic and non-diabetic individuals.

8. The Long-term Outcomes of Sibutramine Effectiveness on Weight (LOSE Weight) study: evaluating the role of drug therapy within a weight management program in a group-model health maintenance organization.

Am J Manag Care. 2004 Jun;10(6):369-76.

Porter JA, Raebel MA, Conner DA, Lanty FA, Vogel EA, Gay EC, Merenich JA. Aventis Pharmaceuticals, Inc, Bridgewater, NJ 08807, USA. julie.porter@aventis.com

OBJECTIVE: To assess the benefit of sibutramine hydrochloride monohydrate within a weight management program.

STUDY DESIGN: Prospective randomized controlled trial in a health maintenance organization.

PATIENTS AND METHODS: Obese patients (n = 588) starting a weight management program were enrolled. Patients were randomly assigned to participate in the program alone or to participate in the program and receive sibutramine for 12 months. Outcome measures were change in weight, body mass index (BMI), percentage body fat, serum lipids, serum glucose, and blood pressure.

RESULTS: At baseline, there was a younger age and higher weight, BMI, and waist circumference in the drug group. There was more degenerative joint disease in the nondrug group. The mean weight loss at 6 months was 6.8 kg (95% confidence interval [CI], -7.4 to -6.1 kg) in the drug group vs 3.1 kg (95% CI, -3.8 to -2.4 kg) (P<.001) in the nondrug group. Weight loss was maintained at 12 months. Significant reductions in BMI, body fat, and waist circumference occurred in the drug group. There were no significant changes in laboratory values or blood pressure. Patients taking sibutramine experienced a significant increase in heart rate (1.7 beats/min [95% CI, 0.5-2.9 beats/min] vs -0.4 beats/min [95% CI, -1.5 to 0.8 beats/min]; P <.004).