Obesity

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roche presentation on rethinking obesity. treating obesity in the same manner as established cardiovascular risk factors

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Obesity

  1. 1. Rethinking Obesity Chris Sainsbury BHF Glasgow Cardiovascular Research Centre
  2. 2. a. lifestyle change b. antihypertensives
  3. 3. a. lifestyle change b. antihypertensives c. both
  4. 4. a. lifestyle change b. antihypertensives c. both (but which do you think is more likely to reduce CV risk?)
  5. 5. ?
  6. 6. ?
  7. 7. what is the evidence in obesity management?
  8. 8. Accepted wisdom Obesity is an environmental / behavioural problem Behavioural therapy is the best way to treat obesity
  9. 9. Challenges Obesity is an environmental / behavioural problem genetic in uences often ignored Behavioural therapy is the best way to treat obesity diet / exercise yields poor results
  10. 10. adapted from Stunkard et al NEJM 1986;314:193-8
  11. 11. in an obeseogenic environment, genetic factors determine who becomes obese
  12. 12. in an obeseogenic environment, genetic factors determine who becomes obese and who becomes very obese
  13. 13. 50 40 30 20 10 0 1995 <25 25-30 30-40 40+
  14. 14. 50 40 30 20 10 0 2003 <25 25-30 30-40 40+
  15. 15. 50 40 30 20 10 0 2015 <25 25-30 30-40 40+
  16. 16. diet / exercise yields poor results (why might this be?)
  17. 17. adapted from Leibel et al NEJM 1995;332:621-628
  18. 18. atkins weight watchers ornish adapted from Dansinger et al JAMA 2005;293:43-53
  19. 19. NEJM 2002;346:393-403
  20. 20. Why do we continue to advocate behavioural therapy? 1 shifting responsibility for failure 2 not historically had e ective drug therapy
  21. 21. Waist circumference Risk of obesity-associated metabolic complications Gender Increased Substantially increased ≥94 cm (~37 in) ≥102 cm (~40 in) Men ≥80 cm (~32 in) ≥88 cm (~35 in) Women
  22. 22. Moderate (~10%) weight loss is bene cial (i.e. 10 kg weight loss from 100 kg bodyweight) ↓ 20–25% total mortality Mortality ↓ 30–40% diabetes-related deaths ↓ 40–50% obesity-related cancer deaths ↓ 10mmHg systolic pressure BP ↓ 20mmHg diastolic pressure Diabetes ↓ >50% in diabetes risk ↓ 30–50% in fasting glucose ↓ 15% in HbA1c Lipids ↓ 10% total cholesterol ↓ 15% LDL-cholesterol ↓ 30% triglycerides ↑ 8% HDL-cholesterol Adapted from Jung R. British Medical Bulletin 1997; 53: 307-321
  23. 23. Licensed products in UK for obesity • Xenical (orlistat)1: • non-centrally acting • gastric and pancreatic lipase inhibitor • reduces dietary fat absorption • Sibutramine2: • centrally acting serotonin noradrenaline reuptake inhibitor • increases satiety • Rimonabant3: • peripheral and centrally acting • selective cannabinoid receptor (CB1) antagonist 1. Xenical Summary of Product Characteristics. May 2006. 2. Reductil Summary of Product Characteristics. November 2005. 3. Acomplia Summary of Product Characteristics. June 2006.
  24. 24. Xenical (orlistat) produces greater weight loss than placebo and diet Active treatment begins Week 0 12 24 36 52 –4 0 –2 Placebo + diet (n=340) Mean weight loss (%) Orlistat + diet (n=343) –4 –6 –6.1% –8 –10 –10.2%* *p<0.001 vs placebo –12 P9791884/August 29th, from Adapted 2007 Sjöström et al. Lancet 1998; 352: 167–72
  25. 25. Xenical (orlistat) significantly reduces waist circumference compared to placebo Placebo + diet (n=266) 108 Xenical + diet (n=265) Waist circumference (cm) 106 104 –2.6 cm 102 * 100 –6.0 cm *p<0.0001 vs placebo 98 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Adapted from Broom I et al. Int J Clin Prac 2002; 56: 494-499. Week P9791884/August 29th, 2007
  26. 26. Effect of weight loss with Xenical (orlistat) on lipid levels in patients with multiple co-morbidities at one year Total-cholesterol LDL-cholesterol 6 Xenical + diet (n=265) +3.8% 4 Placebo + diet (n=266) 2 p<0.0001 Change (%) 0 –0.6% –2 –1.3% –4 p<0.0001 –6 –8 –7.1% Adapted from Broom et al. Int J Clin Pract 2002; 56: 494–9 P9791884/August 29th, 2007
  27. 27. Effect of weight loss with Xenical (orlistat) on blood pressure in hypertensive patients after 1 year Systolic BP* Diastolic BP† 0 Mean change (mmHg) –2 –4 Placebo + diet (n=289) –4.6 –6 –5.6 Xenical + diet (n=339) –8 –7.7 –10 * Baseline SBP ≥140 mmHg –9.4 † Baseline DBP ≥90 mmHg p=0.017 p=0.022 Adapted from Sharma AM & Golay A. J Hypertens 2002; 20: 1873–8 P9791884/August 29th, 2007
  28. 28. Weight loss with Xenical (orlistat) can lead to reductions in the need for concomitant medication Patients Stopped medication 40 with dyslipidaemia Reduced dose Percentage of patients 30 Patients Patients with diabetes with hypertension 20 10 0 Anti-hypertensives Lipid-lowering drugs Adapted from Wirth A. Diab Obes & Metab 2005; 7: 21-27 P9791884/August 29th, 2007
  29. 29. sibutramine sibutramine + lifestyle lifestyle sibutramine + brief lifestyle Wadden et al NEJM 2005 353:2111-2120
  30. 30. follow up duration and long term success
  31. 31. weight loss / exercise / diet / smoking cessation 0 control 1 2 intervention 3
  32. 32. weight loss / exercise / diet / smoking cessation 0 control 1 2 intervention 3
  33. 33. weight loss / exercise / diet / smoking cessation 0 control 1 2 intervention 3
  34. 34. NEJM 2002;346:393-403
  35. 35. JAMA. 1999;281:235-242.
  36. 36. 1 behavioural therapy 2 monotherapies 3 combination therapy 4 pre emptive therapy
  37. 37. 1 behavioural therapy 2 monotherapies 3 combination therapy BP 4 pre emptive therapy
  38. 38. 1 behavioural therapy 2 monotherapies Cholesterol 3 combination therapy 4 pre emptive therapy
  39. 39. 1 behavioural therapy obesity 2 monotherapies 3 combination therapy 4 pre emptive therapy
  40. 40. 1 behavioural therapy 2 monotherapies 3 combination therapy 4 pre emptive therapy BP / chol / obesity / ?
  41. 41. obesity trends - men 5050 45 4040 35 % population 3030 25 2020 15 1010 5 0 1975 1980 1985 1990 1995 2000 2005 2010 2015 1975 1985 1995 2005 2015 Adapted from The Information Centre. Statistics on Obesity, Physical Activity and Diet: England, 2006. London: TIC, 2006.
  42. 42. obesity trends - women 5060 50 40 40 % population 30 30 20 20 10 10 0 1975 1980 1985 1990 1995 2000 2005 2010 2015 1975 1985 1995 2005 2015 Adapted from The Information Centre. Statistics on Obesity, Physical Activity and Diet: England, 2006. London: TIC, 2006.

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