Obesity Continuum of Care: Behavior Modification Through Pharmacotherapy and Surgery

1
Obesity Continuum of Care Behavior Modification
Through Pharmacotherapy and Surgery
Speaker notes included in notes section below
2
Obesity Treatment Guidelines
www.nhlbi.nih.gov
www.naaso.org
3
Obesity Treatment Recommendations
4
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
fitness Specific races and ethnic
groups Clinical Guidelines on the
Identification, Evaluation, and Treatment of
Overweight and Obesity in AdultsThe Evidence
Report. Obes Res 19986(suppl 2).
5
Metabolic Syndrome NCEP ATP III compared to IDF
requires presence of 3 or more criteria
requires central adiposity and presence of 2 more
criteria
6
Metabolic Risk Identified by Hypertriglyceridemic
Waist
waist
TG
waist
TG
waist
TG
waist
TG
Insulin Resistance (HOMA)
Waist 95 cm M 88 cm F TG 128
mg/dl
Men
Men
Women
Women
Age 55-74
Age 18-34

• Cutpoints are lower with increased risk
• Kahn and Valdez. AJCN 200378928-34

7
Obesity Treatment Pyramid
8
A Guide to Selecting Treatment
The Practical Guide. 2000.
9
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?

10
Assessing Readiness

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

11
5 Steps to Behavior Change

• 1. 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.
12
Patients Dietary Intake and Trends

• 70 of American adults say they are eating
  pretty much whatever they want1
• 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/p
ressrelease.cfm?ID979, obtained 3/14/05.
13
New Food Pyramid Dietary Guidelines
www.mypyramid.gov and www.healthierus.gov/dietaryg
uidelines
14
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

15
Dietary Factors to Address
Fat
Fruits and Vegetables
Eating Out
Portion Size
Fiber
Caloric Beverages
16
One Diet Does Not Fit All
Low Calorie Diet
Low Fat Diet
Low Carb Diet
17
Comparison of Popular Diets
Mean Changes in Weight and Cardiac Risk at 12
Months
Dansinger, et al. JAMA 200529343-53.
18
Meal Replacements Promote Long and Short term
Weight Loss
12001500 kcal/d diet prescription A
conventional foods B meal and snack replacement
for 1 meal, 1 snack
Fletchner-Mors et al. Obes Res 20008399.
19

• Do not judge the impact of physical activity by
  weight loss
• Dr. Steve Blair - Cooper Institute
• September 20, 2004

20

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

21
Differences Between Weight Loss and Weight Loss
Maintenance
22
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

23
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 medications 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 drugs 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

24
Antiobesity Drugs Approved for Long-Term Use
How They Work
25
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

26
The Amount of Weight Loss with Sibutramine Is
Related to the Intensity of the Behavioral
Intervention
Weight loss at 6 months
Wadden TA et al. Arch Intern Med
2001161218-227.
27
STORM 77 (ITT) Achieved 5 Weight Loss at
Six Months
Weight Loss
Weight Maintenance
230
Placebo
225
220
215
Body Weight (lb)
210
205
200
Sibutramine
195
0
12
2
4
6
8
10
14
16
18
20
22
24
Month
Same diet, exercise for sibutramine, placebo P
? 0.001, sibutramine vs placebo for weight
maintenance
James WPT et al. Lancet. 20003562119.
28
Weight Loss with Sibutramine Is Associated with
Improvement in Waist Circumference (STORM data)
44
43
Placebo
42
Waist Circumference (in.)
41
40
Sibutramine
39
38
0
12
2
4
6
8
10
14
16
18
20
22
24
Month
NB Same diet and exercise for both sibutramine
and placebo
James WPT et al. Lancet. 20003562119.
29
Weight Loss with Sibutramine Is Associated with
Improvements in Lipids(STORM Data)
Triglycerides
VLDL-Cholesterol
5
5
0
0
Placebo
Placebo
5
5
Change
10
10
Change


?



?
?
?
15

15
?
?
?
Sibutramine
?
?
?
?
Sibutramine
?
?
?
20
20
?
25
25
0
6
12
18
24
0
6
12
18
24
Month Assessed
Month Assessed
HDL-Cholesterol
25


?
?
Sibutramine
20
?
?
?
15
Change
Weight loss months 16 Weight maintenance
months 724 P 0.005 P 0.001 vs placebo
Placebo
10
5
?
?
0
Adapted with permission from James WPT et al.
Lancet. 20003562119.
0
6
12
18
24
Month Assessed
30
Dose Related Effects of Sibutramineon Systolic
Blood Pressure (SBP)
Sibutramine 15 mg n1924
Sibutramine 10 mg n1318
Sibutramine 20 mg n1126
Sibutramine 30 mg n128
Placebo n1944
10
8
6
3.8
Change in SBP (mmHg)
4
2.6
1.0
2
-0.1
-0.1
0
-1
p The shaded area represents doses not approved
for use by the FDA.
Data on file, Abbott Laboratories.
31
Sibutramine Effect on Blood Pressure

• Mean BP changes in recommended dose range is 1
  mm Hg increase
• A few, 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)

• Birkenfeld AL et al. Circulation 2002106
  2459-2465.
• Berube-Parent S et al. IJO 200125 1144-1153.

32
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

33
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

34
Effect of Long-Term Treatment With Orlistat (The
XENDOS Study)
Completers Data
p
Torgerson JS et al, Diabetes Care 2004 27(1)
155-61.
35
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 15293(23)2873-83.
36
Obese Adolescents with 5 and 10 Decrease in
BMI and Body Weight after 1-Year Treatment
Treatment designates orlistat 120 mg three
times a day plus diet or placebo plus diet.
Last observation carried forward.
Chanoine JP, JAMA 2005 Jun 15293(23)2873-83.
37
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.

38
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)

39
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.
198716399.
40
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 AdultsThe Evidence Report. Obes Res
19986(suppl 2).
41
Update Bariatric Surgery

• Currently Popular Procedures

Gastric Bypass
LapBandTM
Restriction
Malabsorption
42
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

43
Bariatric Surgery Side Effects Complications
1 in 200-300 patients in the US die from
bariatric surgery

• 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

Fujioka K, Diabetes Care 28481-484,2005. Shikora
SA. Nutrition in Clinical Practice.
20001513. www.mayoclinic.com. Surgery for
obesity What is it and is it for you?. Accessed
February 15, 2005.
44
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 2005142525-531.
45
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 2005142525-531.