Obesity Continuum of Care: Behavior Modification Through Pharmacotherapy and Surgery

Speaker notes included in notes section below

www.nhlbi.nih.gov

Obesity Treatment Guidelines

www.naaso.org

Obesity Treatment Recommendations

Classification of Overweight and Obesity by BMI, Waist Circumference and

Associated Disease Risks

Additional risks: Large waist circumference (men > 40 in; women > 35 in)Poor aerobic fitnessSpecific races and ethnic groups

Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults—The Evidence Report. Obes Res 1998;6(suppl 2).

Disease Risk Relative to Normal Weight and Waist Circumference

BMI(kg/m2)

Obesity Class

Men (≤102 cm) ≤40 inWomen (≤88 cm) ≤35 in

Men (>102 cm) >40 inWomen (>88 cm) >35 in

Underweight < 18.5 -- --

Normal 18.5 – 24.9 -- --

Overweight 25.0 – 29.9 Increased High

Obesity 30.0 – 34.9 I High Very High

35.0 – 39.9 II Very High Very High

Extreme obesity > 40 III Extremely High Extremely High

Metabolic Syndrome: NCEP ATP III compared to IDF

* requires presence of 3 or more criteria** requires central adiposity and presence of 2 more criteria

Risk Factor ATP III * IDF**

Central Adiposity (defined by waist circumference)

M (waist) > 40 in (> 102 cm) ≥ 37 in (≥ 94 cm)

F > 35 in (> 88 cm) ≥ 31.5 in (≥ 80 cm)

Triglycerides ≥ 150 mg/dL (≥ 1.7 mmol/L)

≥ 150 mg/dL (≥ 1.7 mmol/L)

HDL-C M < 40 mg/dL

(< 1.03 mmol/L)< 40 mg/dL (< 1.03 mmol/L)

F < 50 mg/dL (< 1.0 mmol/L)

< 50 mg/dL (< 1.0 mmol/L)

Blood Pressure ≥ 130/≥ 85 mm Hg ≥ 130/≥ 85 mm Hg

Fasting Glucose ≥ 110 mg/dL (≥ 6.1 mmol/L)

≥ 100 mg/dL (≥ 5.6 mmol/L)

Metabolic Risk Identified by “Hypertriglyceridemic Waist”

Men MenWomen Women

Insu

lin R

esis

tanc

e (

HO

MA

)

Age 18-34 Age 55-74

waist

waist

waist

waist

TG

TG

TG

TG

Waist = 95 cm M 88 cm F

TG = 128 mg/dl

•Cutpoints are lower with increased riskKahn and Valdez. AJCN 2003;78:928-34

Obesity Treatment Pyramid

Surgery

Pharmacotherapy

Lifestyle Modification

Diet Physical Activity

BMI 40

35

30

25

A Guide to Selecting Treatment

The Practical Guide. 2000.

BMI Category

Treatment 25 - 26.9 27 – 29.9 30 – 34.9 35 – 39.9 ≥ 40

Diet, physical activity, and behavior

With co-morbidity

+ + + +

PharmacotherapyWith

co-morbidity+ + +

SurgeryWith

co-morbidity+

Assessing Readiness

• Why now?• What changes will you have to make?• What will change if you lose weight?• What do others think about your weight?• What else is going on in your life?

Assessing Readiness

• We are not good at predicting outcomes.• Patients ultimately make the decision.• Providers assess costs/benefits in a variety of

contexts.

5 Steps to Behavior Change1. Have patient identify specific goals

– Activity (i.e., one specific goal for exercise)

– Intake (i.e., one specific goal for diet)

2. Identify when, where, and how behaviors will be performed

3. Have patient keep record of behavior change (i.e., diet and activity diaries)

4. Follow-up progress at next treatment visit

5. Congratulate patient on successes; do not criticize shortcomings

Wadden & Foster. Medical Clinics of North America, 2000.

Patient’s Dietary Intake and Trends

• 70% of American adults say they are eating “pretty much whatever they want”1

• Caloric intake has increased by 300 calories per person per day from 1985-20001

– Refined grains accounted for 46% of increase– Added fats: 24% of increase– Added sugars: 23% of increase– Fruits and vegetables: 8% of increase– Meat and dairy declined

• Americans will spend 47% of their food dollar in restaurants in 20052

1 Putnam J et al. USDA FoodReview, Vol 25 (3); 2002. 2 www.restaurant.org/pressroom/pressrelease.cfm?ID=979, obtained 3/14/05.

New Food Pyramid &Dietary Guidelines

www.mypyramid.gov and www.healthierus.gov/dietaryguidelines

MyPyramid.gov

• Website designed for easy patient use• MyPyramid plan provides estimates of amounts

of food by a patients entering their age, sex and activity level

• Assessment of food intake and physical activity levels available on MyPyramid Tracker

• Other advice and tips available at “Inside MyPyramid”

Dietary Factors to Address

Fat

Fruits and Vegetables

FiberPortion Size

Caloric Beverages

Eating Out

One “Diet” Does Not Fit All

Comparison of Popular Diets

Dansinger, et al. JAMA 2005;293:43-53.

Mean Changes in Weight and Cardiac Risk at 12 Months

-3.3

-2.2

-10.8

-2.1 -2.5

-3.0

-3.2 -2.9

-10.1

-3.0 -3.3

-8.2

-12

-10

-8

-6

-4

-2

0Weight, kg Waist circumference, cm Total cholesterol, mg/dl

Mea

n C

hang

e

Atkins Zone Weight Watchers Ornish

Meal Replacements Promote Long and Short term Weight Loss

*1200–1500 kcal/d diet prescriptionA: conventional foodsB: meal and snack replacement for 1 meal, 1 snack

Fletchner-Mors et al. Obes Res 2000;8:399.

“Do not judge the impact of physical activity by weight loss”

Dr. Steve Blair - Cooper Institute

September 20, 2004

Why the difference in impact for physical activity between weight loss and weight loss maintenance?

Differences Between Weight Loss and Weight Loss Maintenance

Weight Loss Maintenance of Weight Loss

• Time limited

• Requires a negative energy balance

• Reduced caloric intake is critical

• Physical activity not required for success

• Common

• Life-long

• Requires energy balance at a reduced body weight

• Physical activity is critical for success

• Rare

How Much is Enough?Current Physical Activity

Recommendations• Minimal public health recommendations to improve

health related outcomes– 30 min moderate activity most days of the week (150

minutes/week)– CDC - Centers for Disease Control – ACSM - American College of Sports Medicine – SG - Surgeon General

• Maximize weight loss and prevent weight regain– 45-60 minutes/day

– IOM - Institutes of Medicine– 60-90 minutes/day

– IASO - International Assoc for Study of Obesity– 60 minutes/day (300 minutes/week)

– ACSM - American College Sports Medicine

• Preventing general weight gain– Unclear

Principles of Obesity Medication Use

• Lifestyle interventions are the foundation of medicating for obesity– The benefits of modest (5 - 10% of body weight) should be emphasized

• The behavioral approach should be implemented with knowledge of the medication’s mechanism of action – Orlistat with 30% fat diet– Sibutramine with meal plan that takes advantage of its satiety promotion

• Obesity medications do not cure obesity, just as antihypertensives do not cure hypertension

• Not all patients respond to a weight loss medication. – If the drug’s use is not associated with weight loss within four weeks, it

should be stopped

• Medications work as long as they are used– Weight gain occurs on stopping medications, although there is some

evidence in support of efficacy of intermittent medication

Antiobesity Drugs Approved for Long-Term Use: How They Work

Sibutramine Orlistat• FDA approved 1997

• Induces feeling of satiety– Less preoccupation, feeling

satisfied with less food

– Greater control of food

intake

– Need to monitor BP early in

program

• Once daily with or without

food

• FDA approved 1999

• Reduces absorption of

~30% dietary fat– Fat in diet passes

undigested

– Facilitates weight loss

– GI side effects

• 3 times daily with meals

and a vitamin supplement

recommended

Sibutramine Key Facts

• Multiple large clinical trials demonstrating:• Dose-related weight loss occurs for 6 months• Amount of weight loss related to intensity of behavioral

approach• Efficacy in weight loss maintenance demonstrated ≥ 2

years • Weight loss produces benefits in lipids, body composition

and is associated with mean blood pressure decrease• Trials in patients with hypertension and diabetes

• Favorable side effect profile: • No abuse potential• No valvuloplasty, no PPH

• Cautions• Blood pressure should be monitored• Should not use with MAOIs, erythromycin, ketoconazole

The Amount of Weight Loss with Sibutramine Is Related to the Intensity

of the Behavioral Intervention*

Wadden TA et al. Arch Intern Med 2001;161:218-227.

-5.2

-11.5

-17.1

-20

-18

-16

-14

-12

-10

-8

-6

-4

-2

0

% W

eigh

t Cha

nge

at 6

mon

ths

Sibutramine

Sibutramine+ Group Sessions

Sibutramine+ Group Sessions

+ Meal Replacements

* Weight loss at 6 months

STORM: 77% (ITT) Achieved > 5% Weight Loss at Six Months

James WPT et al. Lancet. 2000;356:2119.

*Same diet, exercise for sibutramine, placebo; P 0.001, sibutramine vs placebo for weight maintenance

230

210

1950 122 4 6 8 10 14 16 18 20 22 24

Month

Bod

y W

eigh

t (lb

)

Placebo

Sibutramine

Weight Loss Weight Maintenance

225

220

215

205

200

Weight Loss with Sibutramine Is Associated with Improvement in Waist Circumference

(STORM data)

NB: Same diet and exercise for both sibutramine and placebo

Sibutramine

44

43

42

41

40

39

38

0 122 4 6 8 10 14 16 18 20 22 24

Wai

st C

ircum

fere

nce

(in.)

Month

Placebo

James WPT et al. Lancet. 2000;356:2119.

Weight Loss with Sibutramine Is Associated with Improvements in Lipids

(STORM Data)

Weight loss = months 1–6; Weight maintenance = months 7–24; *P < 0.001; †P = 0.002; ‡P = 0.005; §P = 0.001 vs placebo

Sibutramine

Placebo

Triglycerides

–25

–20

–15

–10

–5

0

5

0 6 12 18 24

Month Assessed

% C

ha

ng

e

*†*

–25

–20

–15

–10

–5

0

5

0 6 12 18 24

Sibutramine

Placebo

VLDL-Cholesterol

Month Assessed

% C

hange

§‡*

Sibutramine

Placebo

HDL-Cholesterol

0

5

10

15

20

25

0 6 12 18 24

% C

ha

ng

e

Month Assessed

**

Adapted with permission from James WPT et al. Lancet. 2000;356:2119.

-0.1+1.0*

+2.6*

+3.8*

Dose Related Effects of Sibutramineon Systolic Blood Pressure (SBP)

Change in S

BP (

mm

Hg)

Sibutramine20 mgn=1126

Sibutramine30 mgn=128

Sibutramine15 mgn=1924

Sibutramine10 mgn=1318

Placebon=1944

0

2

4

6

8

10

-1 * p < 0.05 compared to placebo

-0.1

Data on file, Abbott Laboratories.Data on file, Abbott Laboratories.

**The shaded area represents doses not approved for use by the FDA.

Sibutramine: Effect on Blood Pressure

• Mean BP changes in recommended dose range is ~ 1 mm Hg increase

• A few, < 5%, have unacceptable blood pressure increases while on sibutramine

• Significant weight loss, > 5%, is associated with mean BP decrease on sibutramine

• BP effects of sibutramine are blocked by beta blockers1

• BP effects of sibutramine are blocked by exercise program2

• In addition to peripheral effects, sibutramine may have central “clonidine-like” sympatholytic effects1

• BP changes are usually seen in the first four weeks of therapy (need to add reference for this)

1. Birkenfeld AL et al. Circulation 2002;106: 2459-2465.2. Berube-Parent S et al. IJO 2001;25: 1144-1153.

Tips for Managing Patients on Sibutramine

• Start at 10 mg once daily• Prescribe a sensible diet

– Meal replacements for two meals and two snacks + one sensible meal per day

– Portion controlled diet with at least three meals per day

• Follow-up: – 4 pounds weight loss in first 4 weeks helps predict success– Monitor blood pressure. Use clinical judgement about

continuing

• Increase dose to increase weight loss, provided BP is well controlled. Decrease dose or discontinue for BP concerns

• Stay within recommended dose range of 5 to 15 mg • Encourage long term use

Orlistat: Key Facts• Multiple large clinical trials demonstrating

• Weight loss occurs for 6 months• Efficacy in weight loss maintenance demonstrated

≥ 4 years • Weight loss produces benefits in glycemic control,

lipids, waist circumference, BP• Trials in persons with diabetes and hypertension• Independent action on LDL cholesterol

• Favorable side effect profile • No abuse potential• No valvulopathy, no PPH

• Cautions• Vitamin supplement required for long term use• May interfere with cyclosporin absorption

• Likely to be available over the counter in 2006

Effect of Long-Term Treatment With Orlistat (The XENDOS Study)

-4.1 kg

-6.9 kg

0 52 104 156 208-12

-9

-6

-3

0Placebo + lifestyle(n=557)

Orlistat + lifestyle(n=853)

Week

Wei

ght

chan

ge (

kg)

p < 0.001 vs placeboTorgerson JS et al, Diabetes Care 2004; 27(1): 155-61.

Completers Data

Effect of Orlistat on Weight and Body Composition in Obese

Adolescents• 54-week multi-center, double-blind, placebo-controlled

study• 539 obese adolescents, aged 12-16 (357 receiving

orlistat 120 mg three times daily, 182 receiving placebo)• Baseline BMI – 2 units > than US weighted mean for the

95th percentile based on age and gender• Patients placed on reduced-calorie diet and behavior

modification program• 65% of patients in each treatment group completed

study

Chanoine JP, JAMA 2005 Jun 15;293(23):2873-83.

Obese Adolescents with ≥ 5% and ≥ 10% Decrease in BMI and Body Weight after 1-

Year Treatment*

Intent-to-Treat Population†

≥ 5% Decrease ≥ 10% Decrease

Orlistat n Placebo n Orlistat n Placebo n

BMI 26.5% 347 15.7% 178 13.3% 347 4.5% 178

Body Weight

19.0% 348 11.7% 180 9.5% 348 3.3% 180

* Treatment designates orlistat 120 mg three times a day plus diet or placebo plus diet.

† Last observation carried forward.

Chanoine JP, JAMA 2005 Jun 15;293(23):2873-83.

Tips for Managing Patients on Orlistat

• Discuss potential bowel effects and mechanism with patient

• Start at 120 mg before each meal• Prescribe a moderate fat diet

– Caution patients about high fat meal or snack

• Metamucil has been shown to reduce bowel effects• For long term use, prescribe a multivitamin• Orlistat can interfere with cyclosporin absorption• Encourage long term use.

Obesity Pharmacotherapy Summary

• Medications approved for long-term use– sibutramine (Meridia)– orlistat (Xenical)

• Medications approved for short-term use– phentermine– others rarely used: mazindol, diethylpropion

• Medications for use in special patients– the depressed obese patient – bupropion (Wellbutrin) and venlafaxine

(Effexor)– type 2 diabetes – metformin , pramlintide (Symlin), exendin-4

(Exenatide)– patients with neuropsychiatric problems – topiramate (Topamax) and

zonisamide (Zonegran)

• Medications in development– rimonabant (Acomplia)

Bariatric Surgery: Recommendations for Patient Selection

• Between ages 18 and 50• Stable preoperative weight for 3-5 years• Smoking cessation for at least 6 weeks• Those with psychiatric history require careful

assessment• Tests to predict success of surgery:

– Personality factors– Eating habits– Motivation

Grace DM. Gastroenterol Clin North Am. 1987;16:399.

Recommendations for Patient Selection- NIH Guidelines

• Motivated subjects with acceptable surgical risks with– BMI ≥ 40 – OR– BMI ≥ 35 with comorbid conditions

Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults—The Evidence Report. Obes Res 1998;6(suppl 2).

Update: Bariatric SurgeryCurrently Popular Procedures

LapBandTM Gastric Bypass

Restriction Malabsorption

Bariatric Surgery: Mechanisms

• Operations dramatically restrict gastric size, reducing nutritional intake

• Some types of surgery decrease the absorption efficiency of nutrients

– Roux-en-Y gastric bypass

– Biliopancreatic diversion (BPD)

• Malabsorption procedures create a greater risk for nutritional deficiencies

Bariatric Surgery: Side Effects & Complications

• Iron deficiency• Vitamin B12 deficiency• Folic Acid deficiency• Dehydration• Vitamin A deficiency• Electrolyte deficiency• Protein deficiency• Hyperparathyroidism• Follow up of nutritional and

metabolic problems after bariatric surgery

• Nausea• Vomiting• Abdominal pain• Constipation• Marginal ulceration• Gallstones• Bleeding ulcer• Obstruction of the stomach outlet

1 in 200-300 patients in the US die from bariatric surgery

Fujioka K, Diabetes Care 28:481-484,2005.Shikora SA. Nutrition in Clinical Practice. 2000;15:13.www.mayoclinic.com. Surgery for obesity: What is it and is it for you?. Accessed February 15, 2005.

Bariatric Surgery: Mortality

• Roux-en-Y gastric bypass surgery appears to have a mortality rate ranging from 0.3% (95% CI, 0.2% to 0.4%) from case series data to 1.0% (95% CI, 0.5% to 1.9%) in controlled trials.

• Adjustable gastric banding appears to have an early mortality rate of 0.4% (95% CI, 0.01% to 2.1%) for controlled trials and 0.02% (95% CI, 0.9% to 0.78%) for case series data.

• No statistically significant difference in mortality seen between procedures.

Snow V.  Ann Int Med 2005;142:525-531.

Surgical Volume and Mortality

• Surgical technique involved a significant learning curve

• Centers that perform more procedures have a lower mortality rate

• One study (Flum D, et al) found surgeons who performed fewer than 20 procedures had patient mortality rates of 5%, as compared with a near 0% mortality for surgeons who had performed 250 or more procedures.

Snow V.  Ann Int Med 2005;142:525-531.