16. Accepted wisdom
Obesity is an environmental / behavioural problem
Behavioural therapy is the best way to treat obesity
17. 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
28. Why do we continue to advocate behavioural therapy?
1 shifting responsibility for failure
2 not historically had e ective drug therapy
29. Waist circumference
Risk of obesity-associated metabolic complications
Gender Increased Substantially increased
โฅ94 cm (~37 in) โฅ102 cm (~40 in)
Men
โฅ80 cm (~32 in) โฅ88 cm (~35 in)
Women
30. Moderate (~10%) weight loss is bene cial (i.e. 10 kg weight loss from 100 kg bodyweight)
โ 20โ25% total mortality
Mortality
โ 30โ40% diabetes-related deaths
โ 40โ50% obesity-related cancer deaths
โ 10mmHg systolic pressure
BP
โ 20mmHg diastolic pressure
Diabetes โ >50% in diabetes risk
โ 30โ50% in fasting glucose
โ 15% in HbA1c
Lipids โ 10% total cholesterol
โ 15% LDL-cholesterol
โ 30% triglycerides
โ 8% HDL-cholesterol
Adapted from Jung R. British Medical Bulletin 1997; 53: 307-321
31. Licensed products in UK for obesity
โข Xenical (orlistat)1:
โข non-centrally acting
โข gastric and pancreatic lipase inhibitor
โข reduces dietary fat absorption
โข Sibutramine2:
โข centrally acting serotonin noradrenaline reuptake
inhibitor
โข increases satiety
โข Rimonabant3:
โข peripheral and centrally acting
โข 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.
32. Xenical (orlistat) produces greater weight loss
than placebo and diet
Active treatment begins
Week
0 12 24 36 52
โ4
0
โ2 Placebo + diet (n=340)
Mean weight loss (%)
Orlistat + diet (n=343)
โ4
โ6 โ6.1%
โ8
โ10 โ10.2%*
*p<0.001 vs placebo
โ12
P9791884/August 29th, from
Adapted 2007 Sjรถstrรถm et al. Lancet 1998; 352: 167โ72
33. Xenical (orlistat) significantly reduces waist
circumference compared to placebo
Placebo + diet (n=266)
108
Xenical + diet (n=265)
Waist circumference (cm)
106
104 โ2.6 cm
102
*
100 โ6.0 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
34. 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
โ0.6%
โ2 โ1.3%
โ4 p<0.0001
โ6
โ8 โ7.1%
Adapted from Broom et al. Int J Clin Pract 2002; 56: 494โ9
P9791884/August 29th, 2007
35. Effect of weight loss with Xenical (orlistat) on blood
pressure in hypertensive patients after 1 year
Systolic BP* Diastolic BPโ
0
Mean change (mmHg)
โ2
โ4
Placebo + diet (n=289)
โ4.6
โ6
โ5.6 Xenical + diet (n=339)
โ8
โ7.7
โ10 * Baseline SBP โฅ140 mmHg
โ9.4 โ Baseline DBP โฅ90 mmHg
p=0.017
p=0.022
Adapted from Sharma AM & Golay A. J Hypertens 2002; 20: 1873โ8
P9791884/August 29th, 2007
36. 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
37. sibutramine
sibutramine + lifestyle
lifestyle
sibutramine + brief lifestyle
Wadden et al NEJM 2005 353:2111-2120