Produced by the Royal College of Physicians of Edinburgh and Royal College of Physicians and Surgeons of Glasgow

OBESITY - A REVIEW OF CURRENT TREATMENTS

  • Professor R Jung, Specialist in Obesity, Diabetes and Endocrinology, Ninewells Hospital and Medical School, Dundee, Scotland
  • Dr A Avenell, Research Fellow Health Services Research Unit, Foresterhill, Aberdeen University, Aberdeen, Scotland

Summary

Obesity has now become a major global health problem and has been associated with a major increase in type 2 diabetes. How can we reduce obesity and what treatments are available? Prof Roland Jung and Dr Alison Avenell review the evidence.

Key Points

  • Obesity is associated with the international epidemic of type 2 diabetes and weight control is the key to prevention.
  • Some nations have made strenuous efforts over decades to curtail the rise of weight of their population (e.g. Sweden) with limited success. No one measure is likely to be effective, but will require a package of simultaneous developments and the necessary research carried out long-term to assess efficacy.
  • # In the treatment of the obese person, weight reduction trials require a follow-up of at least 12 months as short-term trials (e.g. 3-6 months) do not give guidance on long-term efficacy.
  • Low fat or 600kcal deficit diets are as effective as low calorie (1000-1600kcal) diets or very low calorie (<1000kcal) diets for long-term weight control, and reduce the blood lipids, blood glucose, blood pressure and the incidence of diabetes mellitus.
  • High-protein, high-fat, low carbohydrate diets (e.g. the Atkins diet) reduce weight effectively and do not cause elevation of lipids in the first 12 months, but the long-term effects of such diets are unknown.
  • Exercise produces benefits for weight reduction additional to diet, and behavioural therapy and family therapy in adults are beneficial.
  • # Drugs such as orlistat, sibutramine and metformin can reduce weight gain and prevent obesity complications, but need to be used as adjuncts to diet and exercise.
  • Surgery to reduce weight (bariatric surgery) effectively reduces weight and prevents obesity complications, but is best for those with severe obesity especially if associated with diabetes mellitus.

Declaration of interests: Prof Jung has received funding to assist with the employment of a dietitian by Tayside Health Board and has also received lecture fees from Roche. Dr Avenall’s salary (1993-95) was funded by Roche and her Department has also received £500 for a presentation which she gave at a meeting sponsored by Roche.

Leave gormandising; know, the grave doth gape for thee thrice wider than for other men William Shakespeare, Henry IV Part 2; King to Falstaff

Obesity has, at last, reached the political agenda, with the realisation that the epidemic of Type 2 Diabetes, fuelled by obesity, is preventable by weight control. For some decades, Sweden has been at the forefront of the anti-obesity campaign introducing many of the national programmes now being considered as public-policy solutions by other nations. Sweden has advocated and publicised healthy diet and exercise programmes, made widely available low-fat products clearly designated with nutritional information, and major food outlets such as McDonald’s have offered lighter meal options. Television commercials aimed at children under 12 years are restricted, schoolchildren as young as eight years learn to cook healthy meals, sports programmes for youngsters are heavily subsidised and vending machines in schools a rarity. Yet Swedish youngsters show a relentless rise in being overweight and obesity. The prevalence of overweight/obese children in Sweden is 18% (15% overweight and 3% obese) compared to 14% in Germany, 20% in UK (12% overweight and 8% obese) and 26% in USA. Although the measures put in place by Sweden may delay and limit the degree of obesity, it is still a disappointment – but why? Is it general inactivity associated with sedentary activities such as watching television, computers and mobile telephoning? The Scottish Intercollegiate Guidelines Network (SIGN) clinical guideline on the management of obesity in children and young people1 advises fewer than two hours of inactivity as well as at least 30 minutes (preferably 60 minutes) of physical activity per day, in addition to a healthier diet and family involvement. Does worldwide advertising overcome local initiatives? Is it a lack of developmental training of very young children (four to eight years) and their families in healthy eating especially of vegetables and fruit, now being tested in Wales?2 Other ideas abound, including taxing high-fat-density foods, candy and high-energy drinks, introducing many more low-energy versions of popular fast foods and drinks, compulsory smaller portion and low-energy meal availability (at lower prices!) at all food outlets. The important point is that research indicating whether any of these policy issues would be effective, in the long-term, is just not available.

Prevention is crucial but treatment of those people who are obese is essential to prevent disease progression! The popular SIGN clinical guideline on ‘Obesity in Scotland: integrating prevention with weight management’3 gave practical guidance. Health Technology Assessment (UK) has commissioned two recent reports, on obesity surgery (2002),4 and another on the other therapies for obesity (published early 2004).5 The US Preventive Service Task Force has also published in 2003 their recommendations for the screening for obesity of all adults and the value of intensive behavioural interventions comprising diet and exercise to promote sustained weight loss.6

The Health Technology Assessment (HTA) reports have systematically reviewed random controlled trials (RCTs) of at least one year of follow-up, essential as short episodes of weight loss are rarely sustained. Low-fat, or 600 kcal per day deficit, diets were found to be efficacious in 12 RCTs, reducing weight for at least 36 months but not sustained for 60 months. Mean weight loss was 5·3 kg at 12 months and 3·6 kg at 36 months, with significant reduction in the risk factors of blood pressure, lipids and fasting glucose at one year. The clinical outcomes of such a modest weight loss were impressive, with 30% less development of Type 2 diabetes or impaired glucose tolerance (IGT) (Swinburn) at two years, and significantly less antihypertensive medication usage for up to 30 months (Hypertension Optimal Treatment (HOT) trial)7 and an impressive 60% maintenance off hypertension medication (control 35%) in the Dietary Intervention Study of Hypertension trial.8

Low-calorie diets (LCD), i.e. 1,000–1,600 kcal per day, showed no added advantage to either 600 kcal deficit or low-fat diets. Likewise very low-calorie diets (i.e. <1,000 kcal per day) showed no advantage at one year compared with LCD, although short-term weight losses were impressive (13·4 kg) but quickly regained. Similar was noted for the protein sparing modified fast (PSMF). The presently fashionable Atkins diet is similar to PSMF in its high-protein, low-carbohydrate components but is distinguished by a far higher fat content. Therefore, in recent trials it has been compared in total caloric content to conventional LCD where weight loss was significantly improved on Atkins at six months (7% weight loss vs 3·2% LCD) but not at 12 months (4·4% vs 2·5%).9 Interestingly despite a high fat intake, high-density lipoprotein (HDL) and triglycerides were improved at one year but not total cholesterol, low-density lipoprotein (LDL) cholesterol or blood pressure. Long-term effects of such an unusual diet with unrestricted red meat intake, relative lack of vegetables and fruit and high saturated fat, are as yet unknown but subject to much alarm in health circles.

Exercise added to diet is certainly beneficial on weight and is possibly maintained longer than diet (8·2 kg advantage at 36 months in the longest trial). Behavioural therapy is beneficial at 12 months but the limited trial data suggests that its benefit is less well maintained than exercise at 18 and 36 months. All three modalities given together alter outcomes, with the risk of developing hypertension reduced to 0·66 at 18 months in the Trial of Hypertension Prevention 1 (TOHP 1; 1992)10 and to 0·79 at four years in TOHP2 (1997).11 In the Finnish Diabetes Prevention Study there was 58% less Type 2 diabetes at three years in those on diet and exercise.12

Family therapy advocated in children in SIGN 69 was beneficial in five RCTs in adults compared to individual treatment (5·6 kg loss advantage at 24 months), whereas group therapy was similar in effectiveness at 12 months to individual treatment sessions.

Drug treatment with orlistat or sibutramine was effective up to 24 months (3·4 kg loss advantage) with generally improved risk factors and outcomes apart for some evidence of increased blood pressure with sibutramine. The Xenical in the Prevention of Diabetes in Obese Swedish Subjects (XENDOS)13 prevention study using orlistat has recently reported a 37% reduction in Type 2 Diabetes. Metformin, however, used in the United Kingdom Prospective Diabetes study (UKPDS) trial of Type 2 Diabetes14 showed weight maintenance but not weight loss for up to 15 years (usual trend is for weight to rise with time), with HbA1c% reduced by 2·3%, reduced all-cause mortality (odds ratio 0·62) and reduced myocardial infarction mortality (odds ratio 0·51) over ten years. Metformin used in the Diabetes Prevention Programme15 reduced development by 31%, whereas lifestyle intervention was more effective at 58%.

The research so far indicates that even modest maintained weight loss is beneficial but larger weight loss produced by bariatric surgery (gastrointestinal surgery to produce weight loss) has a major impact especially on diabetes development and progression. Bariatric surgery produced weight loss of 23–37 kg for up to eight years with an 84% reduction in Type 2 diabetes. Although blood pressure and cholesterol were improved at two years, blood pressure reduction was not sustained at eight years indicating that, in the long term, diabetes is more influenced by weight than hypertension. The National Institute of Clinical Excellence (NICE)16 in England has reviewed bariatric surgery and has concluded that it is most cost-effective for the severely obese who have diabetes or impaired glucose tolerance (Quality adjusted life year (QALY) £2,329).

The opening quote indicates that, even in the sixteenth century, Shakespeare was well aware of the danger to health of obesity, so is it not timely four centuries later for there to be a major international effort to try to understand and overcome this epidemic? Obesity is not a vagary of fashion but a nutritional disease associated with extensive human suffering and a massive financial cost to society.

Based on a lecture at the St Andrew’s Day Symposium at the Royal College of Physicians of Edinburgh, December 2003.

References

  1. Scottish Intercollegiate Guidelines Network (SIGN). SIGN 69: Management of obesity in childeren and young people. Edinburgh: SIGN; 2003.
  2. Food Dudes Programme
  3. Sign Intercollegiate Guidelines Network (SIGN). Sign 8: Obesity in Scotland: integrating prevention with weight management. Edinburgh: SIGN; 1996.
  4. Clegg AJ, Colquitt J, Sidhu MK et al. The clinical effectiveness and cost-effectiveness of surgery for people with morbid obesity: a systematic review and economic evaluation. Health Technol Assess 2002; 6(12):1-153.
  5. Avenell A, Broom J, Brown TJ et al. Systematic review of the long term effects and economic consequences of treatments for obesity and implications for health improvement. Health Technol Assess. Due to be published early 2004.
  6. US Preventive Services Task Force. Screening for obesity in adults. 2003.
  7. Hansson L, Zanchetti A, Carruthers SG et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet 1998; 351(9118):1755-62.
  8. Blaufox MD, Langford HG, Oberman A et al. Effect of dietary change on the return of hypertension after withdrawal of prolonged antihypertensive therapy (DISH). Dietary Intervention Study of Hypertension. J Hypertens Suppl 1984; 2(3):S179-81.
  9. Foster GD, Wyatt HR, Hill JO et al. A randomised trial of a low carbohydrate diet for obesity (Atkins) New Engl J Med 2003; 348:2082-90.
  10. Batey DM, Kaufmann PG, Raczynski JM et al. Stress management intervention for primary prevention of hypertension: detailed results from Phase I of Trials of Hypertension Prevention (TOHP-I). Ann Epidemiol 2000; 10(1):45-58.
  11. Stevens VJ, Obarzanek E, Cook NR et al. Long-term weight loss and changes in blood pressure: results of the Trials of Hypertension Prevention, phase II. Ann Intern Med 2001; 134(1):1-11.
  12. Kubaszek A, Pihlajamaki J, Komarovski V et al. Promoter polymorphisms of the TNF-alpha (G-308A) and IL-6 (C-174G) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study. Diabetes 2003; 52(7):1872-6.
  13. Torgerson JS, Hauptman J, Boldrin MN et al. 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. Diabetes Care 2004; 27(1):155-61.
  14. Clarke P, Gray A, Adler A et al. Cost-effectiveness analysis of intensive blood-glucose control with metformin in overweight patients with type II diabetes (UKPDS No. 51). Diabetologia 2001; 44(3):298-304.
  15. Diabetes Prevention Program Research Group: reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346:393-403.
  16. Full guidance on the use of surgery to aid weight reduction for people with morbid obesity.