CLINICAL DILEMMAS IN OBESITY
MANAGEMENT
Robert B. Baron MD MS
Professor and Associate Dean
UCSF School of Medicine
Declaration of full disclosure: No conflict of interest
Case 1
50 year old woman, in good health, no
history of cigarettes, in for check up.
BMI 29.
Should you tell her she is overweight?
What further assessment and
treatment should you begin?
CLASSIFICATION OF OVERWEIGHT
AND OBESITY BY BMI
Obesity Class
BMI (kg/m2)
I
II
III
<18.5
18.5 – 24.9
25.0 – 29.9
30.0 – 34.9
35.0 – 39.9
>40
Underweight
Normal
Overweight
Obesity
Extreme Obesity
BMI AND MORTALITY:
Overall
Combined NHANES I, II, and III data set
BMI
<18.5
18.5-<25
25 to <30
30 to <35
≥35
25-59 y
60-69 y
≥70 y
1.38
1.00
0.83
1.20
1.83
2.30
1.00
0.95
1.13
1.63
1.69
1.00
0.91
1.03
1.17
Flegal, JAMA, 2005
An Office-Based Approach
Make the diagnosis (and
communicate it)
Assess readiness for change
Prescribe diet and exercise
Consider medications and
surgery
HEALTH PROFESSIONAL ADVICE
AND WEIGHT LOSS
12,835 adults, BMI over 30 kg/m2, check-up in last year
Random-digit, population-based sample, 50 states
•
42% told by health professional to lose weight
 Those told to lose weight more likely to report
trying to lose weight: OR 2.79 (95% CI 2.53-3.08)
INTENTIONAL WEIGHT LOSS AND
DEATH
Prospective CDC cohort study, 6391 adults, followed for 9 years
•
Those reporting intentional weight loss had 24% reduction in mortality
•
Those reporting unintentional weight loss had 31% higher mortality
•
Those reporting attempted but unsuccessful weight loss also had 20%
reduction in mortality
Gregg, Ann Int Med 2003
METABOLIC SYNDROME
Fulfill 3 or more criteria:
 Waist: men > 102 cm ( > 40 in); women > 88 cm ( > 35
in)
 HDL: men < 40; women < 50
 Triglycerides: ≥150 mg/dl
 BP: ≥130/85 (or use of medications)
 Fasting glucose: ≥110 mg/dl
ICD-9: 277.7
NCEP, JAMA 2001
GOALS OF MANAGEMENT

Be as fit as possible at current weight

Prevent further weight gain

If successful at 1 and 2, begin weight
loss
Case 2
50 year old woman, in good health, in for
check up. BMI 32 with metabolic
syndrome.
She says, “ I have to lose weight, and I
am planning on doing that. I am about
to try the South Beach diet.”
DIET THERAPY
• 48 RCT’S
• Average weight loss 8% over
3-12 months
VLCD’s vs LCD’s:
Meta-analysis of 29 U.S. Studies
• Weight loss studies with > two year f/u
• 13 VLCDs, 14 LCDs
• Mostly observational studies (few RCT’s)
Weight loss (as % of initial weight):
LCDs
VLCDs
1y
7.2
16.1
2y
4.2
9.7
3y
3.5
7.8
4y
2.8
7.0
5y
2.0
6.2
Anderson, Am J Clin Nutr, 2001
COMPARISON OF ATKINS, ORNISH,
WEIGHT WATCHERS, AND ZONE
160 patients, randomly assigned
Intention to treat at 1 year
Wt Loss (kg)
Completers (%)
Atkins
2.1
53
Ornish
3.3
50
WW
3.0
65
Zone
3.2
65
Ornish
6.6
WW
4.6
Zone
4.9
Completers at 1 year
Wt Loss (kg)
Atkins
3.9
Dansinger, JAMA 2005
COMPARISON OF ATKINS, ORNISH,
WEIGHT WATCHERS, AND ZONE
 Each group: 25% lost 5%, 10% lost 10% of initial
weight
 Each diet reduced LDL/HDL by 10%
 No significant effects on BP or glucose
 Weight loss associated with adherence, but not
diet type
 CRP and insulin reductions associated with
weight loss, but not diet
Dansinger, JAMA, 2005
DIET APPROACHES
 Diets
low cal (low fat, low carbohydrate),
meal replacement
 Commercial programs
Weight Watchers™, Jenny Craig™,
TOPS™, Overeaters Anonymous™,
Nutrisystem.com,™ Shapedown,™
The Solution™
 Internet programs (by RDs)
Fitday.com, Dietwatch.com,
Cyberdiet.com, eDiets.com,
Shapeup.org
FITNESS AND MORTALITY
Aerobics Center Longitudinal Study
25,714 men, 44 years old, 14 year observational study
CV death (RR)
normal
Fit
1.0
Not fit
3.1
overweight
1.5
4.5
obese
1.6
5.0
Total death (RR)
normal
Fit
1.0
Not fit
2.2
overweight
1.1
2.5
obese
1.1
3.1
Wei, JAMA 1999
FITNESS AND OBESITY
Nurses Health Study
116,564 women, 24 year observational study
Total death (RR)
Active
Not active
normal
1.00
1.55
overweight
1.91
2.42
Hu FB, NEJM 2004
SUCCESSFUL WEIGHT LOSS
MAINTENANCE
 3000 subjects in National Weight Control
Registry: 30-lb weight loss for 1-year
 Average weight loss 30kg (10 BMI units less),
average weight maintenance 5.5 years
 45 years old, 80% women, 97% Caucasian
 46% overweight as child, 46% one parent obese,
27% both parents
Wing and Hill, Ann Rev Nutr, 2001
SUCCESSFUL WEIGHT LOSS
MAINTENANCE
• High levels of physical activity
• Women 2545 kcal/week, men 3293 kcal/week
• (1-hour moderate intensity per day
• Only 9% report no physical activity
• Diet low in fat, high in carbohydrate
• 1381 kcal day, 24% fat, 19% protein, 56% CHO
• 4.87 meals or snacks/day
• Fast food 0.74/week
• Regular self-monitoring of weight
• 44% weigh once per day; 31% once per week
Wing and Hill, Ann Rev Nutr, 2001
Case 3
46 year old woman, in good health, in for check
up. BMI 42 with diabetes.
In 1996 she lost 20 pounds on phen-fen. She
wants a new weight loss drug and a referral
for weight loss surgery.
“LONG TERM” PHARMACOTHERAPY OF
OBESITY
Review of all RCT’s more than 36 weeks published since 1960
Weight loss in excess of placebo:
% of initial
kg’s
Phen-fen
11.0%
9.6 kg
Phentermine
8.1%
7.9 kg
Sibutramine
5.0%
4.3 kg
Orlistat
3.4%
3.4 kg
Dexfenfluramine
3.0%
2.5 Kg
Fluoxetine
-0.4%
-0.4 kg
Diethyproprion
-1.5%
-1.5 kg
Glazer, Arch Int Med 2001
SIBUTRAMINE ALONE AND WITH LIFESTYLE MODIFICATION
Wadden, T. A. et al. N Engl J Med 2005;353:2111-2120
OFF-LABEL USE
Sertraline – SSRI
– More selective 5-HT uptake inhibitor
– In Phase III trials now
Buproprion – NA re-uptake inhibitor
– RCT of 327 obese pts, 24 weeks;
– Wt. loss: 2% placebo vs. 5% in 300/400 mg
Topiramate – CA inhibitor
– RCT in 385 obese pts; dose-ranging; 24 wks
– Wt loss: -2.6% placebo vs. -5 to -6% w/drug
OTHER DRUGS OFF-LABEL
Amantadine
Other SSRIs (fuvoxamine, venlafaxine, citalopram, others)
H2 blockers (cimetidine)
Metformin
– Wt loss: -2 kg with drug vs. -0 kg with placebo vs. -4 kg
with lifestyle in DPP
Exenatide (Byetta)
- Wt loss: -4-5 kg in open label study at 80+ weeks
Zonisamide – antiepileptic
– Wt loss: -5.9 kg with drug vs. 0.9 kg with placebo
RIMONABANT (Acomplia™)
• 1,507 severely obese people, Europe, 2-years (2005)
rimonabant
placebo
7.3 kg loss
2.5 kg loss
• 3,040 obese people, US, 2-years (2004)
rimonabant
placebo
7.6 kg loss
2.3 kg loss
Year 1 Body
Weight
Placebo
5 mg of Rimonabant
20 mg of Rimonabant
0
-2
-4
-6
-8
-10
0
12
2
4
Weeks
36
52
Year 2 Body
Weight
Placebo/Placebo
20 mg rimonabant/Placebo
20 mg rimonabant/20 mg
0
-2
-4
-6
-8
-10
52
60
68
76
84
Weeks
92
104
RIMONABANT (Acomplia™)
Side Effects
Nausea: 13.7% with drug vs. 5.5% on placebo
Dizziness: double with drug
Diarrhea: double with drug
Depression: 2.8% vs. 1.6%
Drop outs: 19% with drug vs. 13% with placebo
PRINCIPLES OF DRUG THERAPY
•
NIH: BMI > 30 kg/m2 or 27 kg/m2 with co-morbidity (but in
practice almost never)
•
Motivated to begin structured exercise and low calorie diet
•
Begin medications at completion of one month successful
diet and exercise
•
Continue medications only if additional weight loss achieved
in first month with meds
Wouldn’t It Be Easier Just To Have
Surgery?
National Trends in Annual Numbers
of Bariatric Procedures, 1998-2003
Data based on nationwide inpatient
sample
Projection based on preliminary
data from 12 states for 2003
1998
1999
2000
2001
2002
2003
Year
Error bars indicate 95% confidence intervals
Who’s Getting Surgery?
Approved by most payers; cost effective
Recent review indicates more surgeries done in:
– women
– those with private insurance
– those living in wealthier zip codes
Santry HP et al JAMA 2005;294:1909
Types of Surgery
Restrictive
•
•
•
•
Horizontal Gastroplasties
Vertical Banded Gastroplasty (VGB)
Silastic Ring Vertical Gastroplasty (SRVG)
Adjustable Gastric Banding
Malabsorptive
•
•
•
•
Jejunoileal Bypass (JIB)
Biliopancreatic Diversion (BPD)
Duodenal Switch
Long Limb Gastric Bypass
Restrictive with Malabsorptive Component
•
Roux-en-Y Gastric Bypass (RYGPB)
Restrictive Procedures
VBG
Adjustable Gastric Banding
Roux-en-Y GB
BARIATRIC SURGERY META-ANALYSIS
Review of bariatric surgery (136 studies), 1990-2003, 22,092 patients
weight loss (kgs)
BMI decrease
% excess weight loss
Total
-39.71
-14.20
-61.23
Gastric Banding
-28.64
-10.43
-47.45
Gastric Bypass
-43.48
-16.70
-61.56
Gastroplasty
-39.82
-14.20
-68.17
-46.39
-17.99
-70.12
Biliopancreatic diversion
or duodenal switch
Buchwald, JAMA, 2004
Resolution of Comorbidities
Bariatric Surgery – A Systematic Review and Meta-analysis
Buchwald H. et al.
JAMA. 2004; 292(14):1724-37
100
% Resolution Comorbidity
90
80
70
Band
VBG
60
50
GBP
D Switch
40
30
20
10
0
Diabetes
Hyperlipidemia
HTN
Sleep apnea
BARIATRIC SURGERY META-ANALYSIS
Review of bariatric surgery (136 studies), 22,092 patients
Operative Mortality
Gastric Banding
0.1%
Gastric Bypass
0.5%
Gastroplasty
0.1%
Biliopancreatic diversion
or duodenal switch
1.1%
Buchwald, JAMA, 2004
Mortality Rate After Bariatric Surgery
Flum, D. R. et al. JAMA 2005;294:1903-1908.
.
Survival After Bariatric Surgery by Age Group
Flum, D. R. et al. JAMA 2005;294:1903-1908.
LACK OF METABOLIC EFFECTS OF
LIPOSUCTION
• 15 women, before and after liposuction (8
with normal glucose tolerance, 7 with
diabetes)
• Weight loss: 9.1 kg (NLs) and 10.5kg (DM)
• No change in insulin sensitivity of muscle,
liver, or adipose tissue
• No change in C-reactive protein, IL-6, TNF
alpha or adiponectin
• No change BP, glucose, insulin, lipids
Klein, NEJM 2004
The Magic Formula