Obesity and Sibutramine

8/4/2019 Obesity and Sibutramine

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What is Obesity?

Obesity means excess accumulation of fat in

the body

Once it develops it is difficult to cure andusually persists throughout life

Obesity is usually diagnosed on the basis ofcalculation of

Body mass index

Measurement of waist-hip ratio


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Classification of Overweight and Obese byBody Mass Index

BMI (kg/m2)

WHO guidelines Proposed Asia Pacific guidelinesUnderweight < 18.5 < 18.5

Normal 18.5-24.9 18.5-22.9Overweight 25.0-29.9 > 23

At risk - 23-24.9

Obesity 30-34.9 (Class I) 25-29.9 (Class I)

35-39.9 (Class II) > 30 (Class II)

Extremely Obese > 40 (Class III) -

BMI = Weight (kg)

[Height (m)]2


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Waist-to-hip ratio

Ratio =WAIST

HIPS

TO FIND RATIOWaist: Measure atnarrowest point withstomach relaxed

Hips: Measure atfullest point

Desired RatioWomen : 94 cm inmen and >80 cm in women


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Co-morbidities risk associated with different levels of BMI and suggested waistcircumference in adult Asians

Classification BMI Risk of co-morbidities

Waist circumference

< 90 cm (men) > 90 cm (men)

< 80 cm (women) > 90 cm (women)

Underweight < 18.5 Low Average

Normal range 18.5-22.9 Average Increased

Overweight > 23

At risk 23-24.9 Increased Moderate

Obese I 25-29.9 Moderate Severe

Obese II > 30 Severe Very severe


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Obesity An imbalance in energy intake andenergy expenditure

Proteins (20%) BMR (60-65%)

ENERGY INTAKE ENERGY EXPENDITURE

Carbohydrates (55%) Physical activity (25-30%)

Fats (25%)Thermic effeof food (10%


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Classification of obesity as per fat distribution

Android (or abdominal or central, males)-Collection of fat mostly in the abdomen (above the waist)

-apple-shaped

-Associated with insulin resistance and heart disease

Gynoid (below the waist, females)

Collection of fat on hips and buttocks

pear-shaped

-Associated with mechanical problems


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Diseases and conditions forwhich obesity is a risk factor

Coronary artery

disease**

Type II Diabetes

Mellitus***

Hypertension**

Dyslipidemia***

Respiratory disease***

Gout**

Reflux disease

Psychological problems

Gallbladder disease***

Osteoarthritis**

Infertility*

Venous circulatory disease

Increased anaesthetic risk* Low back pain*

Polycystic ovary disease*

Cancer* (ovarian, breast,

endometrial, gallbladder,prostate, colon)


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Prevalence of overweight and obesity in different incomegroups of Delhi (Nutrition Foundation of India Study)

Prevalence (%)

Slums Middle-Class Total

Overweight (BMI > 25)Males ND ND 19.6Females ND ND 44.5

Obesity (BMI > 30)Males 1 32.3 NDFemales 4 50 ND

Abdominal obesity

Males ND 49.7 NDFemales ND 34.9 ND

ND: Not determined

http://www.nutritionfoundationin.org/NEW/OBESITY.


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The Five City Study

n=3257; aged 25-64 yrs

Cities: Moradabad (n=902), Trivandrum (n=760), Calcutta (n=410), Nagpur(n=405), Bombay (n=780)

Social Class BMI>27 WHR>0.85 Sedentary life style

I (n=985) 21.2% 96.9% 92.2%

II (n=790 16.4% 57.2% 71.4%

III (n=674) 8.9% 39.3% 42.3%

IV (n=602) 3.0% 11.9% 14.9%

V (n=206) 3.8% 8.7% 8.7%

Int J Cardiol 1999;69:139-147


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Advantages of weight loss

Weight loss of 0.5-9 kg (n=43,457) associated with

53% reduction in cancer-deaths, 44% reduction indiabetes-associated mortality and 20% reduction intotal mortality

Survival increased 3-4 months for every kilogram of

weight loss Reduced hyperlipidemia, hypertension and insulin

resistance

Improvement in severity of diseases

Person feels fit and mentally more active


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Treatment goals

Prevention of further weight gain

Weight loss to achieve a realistic, target BMI

Long-term maintenance of a lower body-weight


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How much weight loss is significant?

A 5-10% reduction in weight (within 6 months) and

weight maintenance should be stressed in any weight

loss program and contributes significantly to

decreased morbidity


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Diet Activity Drugs VLCD Surgery

BMI 23-25

No risk factors

DM/CHD/HT/HL

-

BMI 25 30

No risk factors

DM/CHD/HT/HL

(consider)

BMI > 30

No risk factors

DM/CHD/HT/HL

(insevere)

(considerin severe

Approaches to obesity management


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Drug therapy

Appetite suppressants

Adrenergic agents (e.g. amphetamine, methamphetamine,phenylpropanol amine, phentermine)

Serotonergic agents (e.g. fenfluramine, dexfenfluramine,SSRIs like sertraline, fluoxetine)

Thermogenic agents ephedrine, caffeine

New ones

Sibutramine ; Orlistat

Sib i i hibi i d


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Noradrenaline Serotonin

Sibutramine inhibits serotonin andnoradrenaline reuptake


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STORM Study : Effect of sibutramine on weight loss

98

104

102100

96

94

9290

0 12 22 2420181614108642

Placebo

Sibutramine

Month

Weight loss Weight maintenance

B

odyweight(kg)

Lancet 2000; 356:2119-2125


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STORM Study:

Effect on Waist Circumference and Waist/Hip Ratio

-9.2

-4.5

-10

-9

-8

-7

-6

-5

-4

-3

-2

-1

0

Sibutramine Placebo

Decreaseinwaist

circumference(cm)

-1.2

0.8

-1.5

-1

-0.5

0

0.5

1

Sibutramine Placebo

Change

(a) Waist Circumference (b) Waist/Hip Ratio


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STORM Study : Effects on lipids

5

0

-5

-10-15

-20

-25

Placebo

Sibutramine

Triglycerides

%change

00 2418126

50

-5

-10

-15

-20

-25

Placebo

Sibutramine

VLDL cholesterol

180 24126

%change

Lancet 2000; 356:2119-2125


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STORM Study : Effects on lipids (Contd.)

180 24126

25

20

15

10

5

0

HDL cholesterol

%

change Sibutramine

Placebo

Month of assessment

Weightloss

Weightmaintenance

Lancet 2000; 356:2119-21

30


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STORM study: Conclusions

Almost all patients who persist with a weight

management program consisting ofsibutramine, diet and exercse can achieve atleast a 5% weight loss with sibutramine

Over half can lose more than 10% weightwithin 6 months

Weight loss was sustained in most patients

continuing therapy for two years


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Sibutramine vs. Dexfenfluramine

-3.2

-4.5-5

-4.5

-4

-3.5

-3

-2.5

-2

-1.5

-1

-0.50

Weightlo

ss(kg)

Sibutramine 10 mg Dexfenfluramine 30 mg

n=226; 12 wks

Int J Obes 1995; 19. Suppl 2: 144

Adverse effects occurring in >5% of patients treated


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Adverse effects occurring in >5% of patients treatedwith Sibutramine compared with placebo

Sibutramine % Placebo %

Adverse Effects Incidence (n=2068) Incidence (n=884)

Headache 30.3 18.6

Dry Mouth 17.2 4.2

Anorexia 13.0 3.5

Constipation 11.5 6.0

Insomnia 10.7 4.5

Dizziness 7.0 3.4

Nausea 5.9 2.8

Nervousness 5.2 2.9

Dyspepsia 5.0 2.6Ann Pharmacother 1999;33:968-978

STORM Study :


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STORM Study :Withdrawals due to BP increase

Dose of Sibutramine % patients who

withdrew due to

increase in BP

10 mg 1%

15 mg 2%

20 mg 3%

Lancet 2000; 356:2119-21

I di i & D


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Indications & Dosage

Recommended for obese patients with a BMI > 30

kg/m2

or > 27 kg/m2

in the presence of other riskfactors (e.g. hypertension, diabetes, dyslipidemia)

In Indian patients, sibutramine could be consideredin patients with BMI > 25 kg/m2 or those with BMI of

23 kg/m2

with comorbid conditions

Recommended starting dose is 10 mg once daily.

If there is inadequate weight loss, the dose may betitrated after four weeks to a total of 15 mg once

daily. The 5 mg dose should be reserved for patients who

do not tolerate the 10 mg dose.

Obesity and Sibutramine

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