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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.

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clinical dilemmas in obesity management
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
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
CLASSIFICATION OF OVERWEIGHT AND OBESITY BY BMI
  • Obesity Class BMI (kg/m2)

Underweight <18.5

Normal 18.5 – 24.9

  • Overweight 25.0 – 29.9
  • Obesity I 30.0 – 34.9
  • II 35.0 – 39.9
  • Extreme Obesity III >40
bmi and mortality overall
BMI AND MORTALITY: Overall
  • Combined NHANES I, II, and III data set
  • BMI 25-59 y 60-69 y ≥70 y
  • <18.5 1.38 2.30 1.69
  • 18.5-<25 1.00 1.00 1.00
  • 25 to <30 0.83 0.95 0.91
  • 30 to <35 1.20 1.13 1.03
  • ≥35 1.83 1.63 1.17

Flegal, JAMA, 2005

an office based approach
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
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
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
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
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
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
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
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):
  • 1y 2y 3y 4y 5y
  • LCDs 7.2 4.2 3.5 2.8 2.0
  • VLCDs 16.1 9.7 7.8 7.0 6.2

Anderson, Am J Clin Nutr, 2001

comparison of atkins ornish weight watchers and zone
COMPARISON OF ATKINS, ORNISH, WEIGHT WATCHERS, AND ZONE

160 patients, randomly assigned

  • Intention to treat at 1 year
  • AtkinsOrnishWWZone
  • Wt Loss (kg) 2.1 3.3 3.0 3.2
  • Completers (%) 53 50 65 65
  • Completers at 1 year
  • AtkinsOrnishWWZone
  • Wt Loss (kg) 3.9 6.6 4.6 4.9

Dansinger, JAMA 2005

comparison of atkins ornish weight watchers and zone14
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
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
FITNESS AND MORTALITYAerobics Center Longitudinal Study

25,714 men, 44 years old, 14 year observational study

  • CV death (RR)
  • normal overweight obese
  • Fit 1.0 1.5 1.6
  • Not fit 3.1 4.5 5.0
  • Total death (RR)
  • normal overweight obese
  • Fit 1.0 1.1 1.1
  • Not fit 2.2 2.5 3.1

Wei, JAMA 1999

fitness and obesity nurses health study
FITNESS AND OBESITYNurses Health Study

116,564 women, 24 year observational study

  • Total death (RR)
  • normal overweight
  • Active 1.00 1.91
  • Not active 1.55 2.42

Hu FB, NEJM 2004

successful weight loss maintenance
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 maintenance19
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
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
“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

slide22

SIBUTRAMINE ALONE AND WITH LIFESTYLE MODIFICATION

Wadden, T. A. et al. N Engl J Med 2005;353:2111-2120

off label use
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
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
RIMONABANT (Acomplia™)
  • 1,507 severely obese people, Europe, 2-years (2005)
  • rimonabant 7.3 kg loss
  • placebo 2.5 kg loss
  • 3,040 obese people, US, 2-years (2004)
  • rimonabant 7.6 kg loss
  • placebo 2.3 kg loss
slide26

Placebo

5 mg of Rimonabant

20 mg of Rimonabant

0

12

24

36

52

Year 1 Body Weight

Change From Baseline, kg

Weeks

slide27

Placebo/Placebo

20 mg rimonabant/Placebo

20 mg rimonabant/20 mg

Year 2 Body Weight

Change From Baseline, kg

52

60

68

76

84

92

104

Weeks

rimonabant acomplia side effects
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
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
slide31

Projection based on preliminary data from 12 states for 2003

1998

1999

2000

2001

2002

2003

National Trends in Annual Numbers

of Bariatric Procedures, 1998-2003

Data based on nationwide inpatient sample

No. of Procedures

Year

Error bars indicate 95% confidence intervals

who s getting surgery
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
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)
slide34

Restrictive Procedures

Roux-en-Y GB

Adjustable Gastric Banding

VBG

bariatric surgery meta analysis
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
  • Biliopancreatic diversion
  • or duodenal switch -46.39 -17.99 -70.12

Buchwald, JAMA, 2004

bariatric surgery meta analysis37
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

slide38

Mortality Rate After Bariatric Surgery

Flum, D. R. et al. JAMA 2005;294:1903-1908.

.

slide39

Survival After Bariatric Surgery by Age Group

Flum, D. R. et al. JAMA 2005;294:1903-1908.

lack of metabolic effects of liposuction
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