Transcript Hot Topics in Obesity Treatment - Dr. Moulton

Hot Topics in Obesity Treatment
Prevalence of Overweight and
Obesity Among US Adults
80
Overweight or obese
Overweight
(BMI 25.0)
(BMI 25.0-29.9)
Obese
(BMI 30.0)
64
60
56
Up 100%
in 20 years
47
% 40
34
33
32
31
23
20
0
15
NHANES II*
1976-1980
(n=11,207)
NHANES III
1988-1994
(n=14,468)
NHANES†
1999-2000
(n=3601)
NHANES=National 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. 2002;288:1723-1727.
Binge Eating
• Could there be a survival advantage to being
able to binge or eat more in an environment
with limited food?
Lateral
Hypothalamic
area
Paraventricular
Nucleus
Pituitary
Forebrain
Adrenals
Y1-receptor
Feeding behavior
Metabolic status
save calories
burn calories
MC4R
POMC
NPY
Ghrelin
Stomach
Insulin
Pancreas
MSH
PYY
Intestines
Leptin
Adipose
tissue
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
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 348:12, 2003.
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 348:12, 2003.
Homozygous Mutation in
Melanocortin-4 Receptor Gene
Sibling
With
Mutation
Farooqi IS et al. N Engl J Med. 2003;348:1085-1095.
Sibling
Without
Mutation
MC4R Mutations
• Mutations carriers were:
– Severely obese
– Increased lean mass
– Increased linear growth
– Severe hyper-insulinemia
• Homozygotes were more severely effected than
heterozygotes
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
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
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?
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
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. 1992;12:365-373. Spitzer RL et al. Int J Eat Disord.
1992;11:191-203.
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.
2001;81:1001-1014. Williamson DA, Martin CK. Eat Weight Disord. 1999;4:103-114.
BED and Depression
Patients with Depression (%)
60
Obese BED
Obese Non-BED
50
40
30
20
10
0
Major Depression
Yanovski SZ, et al. Am J Psychiatry. 1993; 150:1472-1479.
Dysthmia
Binge Eating and Overweight
Binge eaters
Nonbingers
% of Subjects
40
30
20
10
0
23-24
24-25
25-27
27-28
28-30
BMI Category
Telch CF et al. Int J Eat Disord. 1988;7:115-119.
30-31
31-34
34-42
Frequency of Binge Eating in BN
Placebo
Fluoxetine hydrochloride 20 mg/d
Fluoxetine hydrochloride 60 mg/d
Median Change,
% of Episodes
0
20
40
60
80
0
1
2
3
4
5
6
7
Study Week
Fluoxetine Bulimia Nervosa Collaborative Study Group. Arch Gen Psychiatry. 1992;49:139-147.
8
Fluoxetine in BED
Mean Binges/Week
Mean Binges/week
7
6.1
6
Placebo
5 6.0
Fluoxetine
4
3
2.7
2
1.8
1
0
0
1
2
3
4
5
6
Weeks
P = 0.03
Arnold LM et al. J Clin Psychiatry. 2002;63:1023-1028.
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
– Randomized
– Completed
n = 549
n = 304
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.
Sibutramine in BED
Binge Days Per Week
Baseline
3.0
Weight Change
Placebo
Endpoint
3.0
2.8
0
-0.5
-1
2.5
1.1
1.0
kg
Days
2.0
1.5
0.6
0.5
0.0
Placebo
Sibutramine
Sibutramine
-1.5
-2
-2.5
-3
-3.5
-4
-4.5
-5
-0.9
-4.4
Wilfley DE et al. Presented at: the Eating Disorders Research Society Annual Meeting; Charleston,
South Carolina; November 20-22, 2002.
Intermittent Drug Therapy
Effect of Continuous and Intermittent Phentermine
Therapy on Body Weight
0
Weight Loss (lbs)
-4
Continuous
Placebo
-8
-12
-16
-20
Continuous
Phentermine
-24
Alternate Phentermine
and Placebo
-28
-32
0
4
8
12
16
20
24
Time (weeks)
Munro JF et al. Brit Med J 1:352, 1968.
28
32
36
Effect of Continuous vs Intermittent
Sibutramine Therapy on Body Weight
Body Weight Change (kg)
0
Placebo
Intermittent sibutramine
Continuous sibutramine
-2
-4
-6
-8
Run-in
period
-10
0
4
8
12
Sibutramine dose = 15 mg/d
Wirth and Krause. JAMA 2001;286:1331.
16
20 24 28 32
Time (wk)
36 40
44
48
Pharmacologic and Surgical Management of
Obesity
in Primary Care:
A Clinical Practice Guideline
from the ACP
Ann Intern Med 2005;142:525-531.
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
“Off-label” Use of Medications for
Weight Loss
• Bupropion
• Fluoxetine
• Sertraline
• Topiramate
• Zonisamide
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
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
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
ACP Guidelines
Recommendation #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
ACP Guidelines
Recommendation #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
ACP Guidelines
Recommendation #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
ACP Guidelines
Recommendation #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
ACP Guidelines
Recommendation #5
• Patients should be referred to high-volume
centers with surgeons experienced in bariatric
surgery
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.
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
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
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
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
Side Effects & Complications
1 in 200-300 patients in the US die from bariatric surgery
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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 28:481-484,2005
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Nausea
Vomiting
Abdominal pain
Constipation
Marginal ulceration
Gallstones
Bleeding ulcer
Obstruction of the stomach outlet
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.