Hot Topics in Obesity Treatment

1
Hot Topics in Obesity Treatment
2
Prevalence of Overweight and Obesity Among US
Adults
(BMI ?25.0)
(BMI 25.0-29.9)
(BMI ?30.0)
Up 100 in 20 years
NHANES II1976-1980(n11,207)
NHANES 1999-2000(n3601)
NHANES III1988-1994(n14,468)
NHANESNational Health and Nutrition Examination
Survey. Age-adjusted by the direct method to the
year 2000 US Bureau of the Census estimates
using the age groups 20-34, 35-44, 45-54, 55-64,
and 65-74 years Flegal KM et al. JAMA.
20022881723-1727.
3
Binge Eating

• Could there be a survival advantage to being able
  to binge or eat more in an environment with
  limited food?

4
Lateral Hypothalamic area
Pituitary Forebrain Adrenals
Paraventricular Nucleus
Feeding behavior Metabolic status save
calories burn calories
Y1-receptor
MC4R
Insulin Pancreas
POMC MSH
NPY
Leptin Adipose tissue
PYY Intestines
Ghrelin Stomach
5
Binge and MC4R Gene

• Two articles in the NEJM March 2003
• Branson 5.1 of obese had MC4R gene mutations
• Farooqi 5.8 of obese had MC4R gene mutations
• All mutation carriers reported binge eating

6
Binge Eating

• 469 morbid obese Caucasian patients
• 79 female
• Found 24 pts (5.1) with a mutation of the MC4R
• Basically a defective receptor
• All 24 of these pts (100) had binge eating
• Only 14 of matched controls had binging

NEJM 34812, 2003.
7
Binge Eating

• 500 morbid obese children
• Found 29 pts (5.8) with a mutation of the MC4R
• Basically a defective receptor
• All 29 of these patients had hyperphagia
• Compared to unaffected siblings they ate three
  times as much food at a single meal
• Meal size corrected for lean body mass

NEJM 34812, 2003.
8
Homozygous Mutation in Melanocortin-4 Receptor
Gene
Farooqi IS et al. N Engl J Med.
20033481085-1095.
9
MC4R Mutations

• Mutations carriers were
• Severely obese
• Increased lean mass
• Increased linear growth
• Severe hyper-insulinemia
• Homozygotes were more severely effected than
  heterozygotes

10
Binge Eating Disorder
Definition of a Binge Episode

• Eating an amount of food that is definitely
  larger than most people would eat in similar
  circumstances during a similar period of time
  (eg, 2x a normal portion in 2 hours)
• A sense of lack of control during the episodes
• Sense of inability to stop or control eating
• Marked distress about the binge eating
• Women yes, men often not
• Binge eating is a provisional DSM code at this
  time

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Secondary Binge Criteria

• Eat alone (closet eating)
• Eat when not hungry
• Eat fast
• Eats until uncomfortably full
• Feeling of guilt or un-happiness after eating
• Loose criteria different for men and women

12
Questions for the Clinician to Ask Patients Who
Might Have Binge Eating Disorder

• Do you ever have episodes of eating where you
  feel out of control or that you just could not
  stop yourself?
• Do you ever eat large portions of food that would
  clearly be larger portions that other persons
  might eat in a similar circumstance?

13
Diagnostic Criteria for Bulimia Nervosa (BN)

• Recurrent episodes of binge eating with loss of
  control
• Recurrent inappropriate compensatory behavior to
  prevent weight gain
• Binge eating and inappropriate compensatory
  behavior both occur, on average, at least twice a
  week for 3 months
• Self-evaluation is unduly influenced by body
  shape and weight

14
Prevalence of BED in Community Samples

• BED is found in 2 to 3 of adults
• About half are obese

Bruce B, Agras WS. Int J Eat Disord.
199212365-373. Spitzer RL et al. Int J Eat
Disord. 199211191-203.
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Prevalence of BED in Clinical Samples

• BED in obese treatment seekers
• 7.6 to 18.8 (rigorously defined)
• 20 to 40 (broadly defined)
• BED in Overeaters Anonymous 70
• BED in bariatric surgery seekers 25 to 50

Stunkard AJ. In Handbook of Obesity Treatment.
2002. Wadden TA et al. Surg Clin N Am.
2001811001-1014. Williamson DA, Martin CK. Eat
Weight Disord. 19994103-114.
16
BED and Depression
Yanovski SZ, et al. Am J Psychiatry. 1993
1501472-1479.
17
Binge Eating and Overweight
Telch CF et al. Int J Eat Disord. 19887115-119.
18
Frequency of Binge Eating in BN
Fluoxetine Bulimia Nervosa Collaborative Study
Group. Arch Gen Psychiatry. 199249139-147.
19
Fluoxetine in BED
Mean Binges/Week
P 0.03
Arnold LM et al. J Clin Psychiatry.
2002631023-1028.
20
Sibutramine in BED

• Placebo-controlled, randomized, double-blind
  trial
• 15 mg/d
• 4-week placebo run-in 6-month double-blind
  treatment
• Placebo run-in n 549
• Randomized n 304
• Completed n 189
• Baseline values determined after placebo run-in
• Outcome measures
• Binge frequency and weight
• A significant difference from placebo was
  achieved for both outcomes

Wilfley DE et al. Presented at the Eating
Disorders Research Society Annual Meeting
Charleston, South Carolina November 20-22, 2002.
21
Sibutramine in BED
Binge Days Per Week
Weight Change
Wilfley DE et al. Presented at the Eating
Disorders Research Society Annual Meeting
Charleston, South Carolina November 20-22, 2002.
22
Intermittent Drug Therapy

23
Effect of Continuous and Intermittent Phentermine
Therapy on Body Weight
Munro JF et al. Brit Med J 1352, 1968.
24
Effect of Continuous vs Intermittent Sibutramine
Therapy on Body Weight
0
Placebo Intermittent sibutramine Continuous
sibutramine
-2
-4
Body Weight Change (kg)
-6
-8
Run-in period
-10
0
4
8
12
16
20
24
28
32
36
40
44
48
Time (wk)
Sibutramine dose 15 mg/d
Wirth and Krause. JAMA 20012861331.
25
Pharmacologic and Surgical Management of Obesity
in Primary Care A Clinical Practice Guideline
from the ACP

• Ann Intern Med 2005142525-531.

26
Medications Used for Weight Loss

• Phentermine
• Diethylpropion
• Sibutramine
• Orlistat
• Approved by the FDA for short term weight loss
• Approved by the FDA for weight loss and weight
  maintenance

27
Off-label Use of Medications for Weight Loss

• Bupropion
• Fluoxetine
• Sertraline
• Topiramate
• Zonisamide

28
Coverage of Weight Loss Medications

• Typically not covered as a general rule
• Although see 30 to 40 coverage
• Typically covered medical conditions that get
  coverage of weight loss medications
• Morbid obesity
• With the threat of bariatric surgery
• Diabetes
• Patients with BMI of 35 with co-morbid
  condition
• Metabolic syndrome

29
Paperwork Billing Codes

• Very rarely covered by health insurances
• Obesity 278.00
• Usually paid billing codes
• Morbid obesity 278.01
• Dysmetabolic Syndrome 277.7
• Impaired fasting glucose 790.21
• Impaired GTT 790.22

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ACP Guidelines

• 5 recommendations based on the evidence report
  and accompanying background papers developed by
  the Southern California Evidence-Based Practice
  Center
• The ACP recommends all clinicians refer to these
  guidelines as part of an overall strategy for
  managing overweight and obese patients
• Overall strategy should always include
  appropriate diet and exercise
• Target audience is patients with BMIs of above 30

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ACP GuidelinesRecommendation 1

• Clinicians should counsel all patients with a BMI
  above 30 on lifestyle and behavior modifications
  such as appropriate diet and exercise
• Patient goals should be individually determined

32
ACP GuidelinesRecommendation 2

• Pharmacologic therapy can be offered to patients
  who have failed diet and exercise alone
• Doctor-patient discussion of side effects, long
  term safety data, and temporary nature of weight
  loss achieved with medications should occur
  before medication initiation

33
ACP GuidelinesRecommendation 3

• Medication choices for the obese patient include
  sibutramine, orlistat, phentermine,
  diethylpropion, fluoxetine and bupropion
• The choice of drug should be dependent on the
  side effect profile and the patients tolerance of
  the side effects

34
ACP GuidelinesRecommendation 4

• Surgery should be considered as a treatment
  option for patients with a BMI over 40 who
• Instituted but failed an adequate exercise and
  diet program (with or without adjunctive drug
  therapy)
• AND
• Present with obesity-related comorbid conditions
  such as hypertension, impaired glucose tolerance,
  diabetes mellitus, hyperlipidemia and obstructive
  sleep apnea
• Doctor-patient discussion of surgery should
  include long term side effects

35
ACP GuidelinesRecommendation 5

• Patients should be referred to high-volume
  centers with surgeons experienced in bariatric
  surgery

36
Bariatric Surgery
37
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.
38
Types of Surgery Gastric Bypass

• Roux-en-Y gastric bypass is the most popular in
  the US
• Pouch can be created with staples or complete
  division
• Long-term weight loss of 50 of excess body
  weight
• Moving Roux limbs distally creates more rapid
  weight loss
• Malabsorption problems may be exacerbated

39
Types of Surgery Gastroplasty

• Vertical banded gastroplasty now the preferred
  type of gastroplasty
• Less enlargement over time
• Produces weight loss, but usually less than
  gastric bypass

40
Types of Surgery Gastric Banding

• Problems with original gastric band
• Pouch too large or small
• Adjustable gastric band developed in the 1980s
• Controls restriction by injection/withdrawal of
  saline
• May be performed laparoscopically

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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

42
Side Effects Complications
1 in 200-300 patients in the US die from
bariatric surgery

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

• 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 K. Fujioka 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.