CLINICAL DILEMMAS IN OBESITY CLINICAL DILEMMAS IN OBESITY MANAGEMENTMANAGEMENT

Robert B. Baron MD MSRobert B. Baron MD MS

Professor and Associate Dean Professor and Associate Dean

UCSF School of MedicineUCSF School of Medicine

Declaration of full disclosure: No conflict of interest

Case 1Case 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)

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

Flegal, JAMA, 2005

BMI AND MORTALITY: BMI AND MORTALITY: OverallOverall

Combined NHANES I, II, and III data set

BMI 25-59 y 60-69 y ≥70 y

<18.5 1.38 2.30 1.6918.5-<25 1.00 1.00 1.0025 to <30 0.83 0.95 0.9130 to <35 1.20 1.13 1.03≥35 1.83 1.63 1.17

An Office-Based ApproachAn 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)

Gregg, Ann Int Med 2003

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

NCEP, JAMA 2001

METABOLIC SYNDROMEMETABOLIC 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

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 2Case 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 THERAPYDIET THERAPY

• 48 RCT’S

• Average weight loss 8% over 3-12 months

Anderson, Am J Clin Nutr, 2001

VLCD’s vs LCD’s: VLCD’s vs LCD’s: Meta-analysis of 29 U.S. StudiesMeta-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

Dansinger, JAMA 2005

COMPARISON OF ATKINS, ORNISH, COMPARISON OF ATKINS, ORNISH, WEIGHT WATCHERS, AND ZONEWEIGHT WATCHERS, AND ZONE

Intention to treat at 1 year Atkins Ornish WW Zone

Wt Loss (kg) 2.1 3.3 3.0 3.2Completers (%) 53 50 65 65

Completers at 1 year Atkins Ornish WW Zone

Wt Loss (kg) 3.9 6.6 4.6 4.9

160 patients, randomly assigned

Dansinger, JAMA, 2005

COMPARISON OF ATKINS, ORNISH, COMPARISON OF ATKINS, ORNISH, WEIGHT WATCHERS, AND ZONEWEIGHT 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

DIET APPROACHESDIET APPROACHES Diets

low cal (low fat, low carbohydrate), meal replacement

Commercial programsWeight 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

Wei, JAMA 1999

FITNESS AND MORTALITYFITNESS AND MORTALITYAerobics Center Longitudinal StudyAerobics Center Longitudinal Study

CV death (RR) normal overweight obese

Fit 1.0 1.5 1.6Not fit 3.1 4.5 5.0

Total death (RR) normal overweight obese

Fit 1.0 1.1 1.1Not fit 2.2 2.5 3.1

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

Hu FB, NEJM 2004

FITNESS AND OBESITYFITNESS AND OBESITYNurses Health StudyNurses Health Study

Total death (RR)

normal overweight Active 1.00 1.91

Not active 1.55 2.42

116,564 women, 24 year observational study

Wing and Hill, Ann Rev Nutr, 2001

SUCCESSFUL WEIGHT LOSS SUCCESSFUL WEIGHT LOSS MAINTENANCEMAINTENANCE

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 SUCCESSFUL WEIGHT LOSS MAINTENANCEMAINTENANCE

• 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

Case 3Case 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.

Glazer, Arch Int Med 2001

“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

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

SIBUTRAMINE ALONE AND WITH LIFESTYLE MODIFICATION

OFF-LABEL USESertraline – 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 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

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Placebo

5 mg of Rimonabant

20 mg of Rimonabant

Weeks

Year 1 Body Weight

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52 60 76 92 104

Placebo/Placebo

20 mg rimonabant/Placebo

20 mg rimonabant/20 mg

Weeks

Year 2 Body Weight

8468

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 THERAPYPRINCIPLES 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?

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National Trends in Annual NumbersNational Trends in Annual Numbers of Bariatric Procedures, 1998-2003of Bariatric Procedures, 1998-2003

1998 1999 2000 2001 2002 2003

Data based on nationwide inpatient sampleProjection based on preliminary data from 12 states for 2003

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

VBGVBG Adjustable Gastric Banding Roux-en-Y GB

Buchwald, JAMA, 2004

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

Resolution of Comorbidities

0

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Diabetes Hyperlipidemia HTN Sleep apnea

Band

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tyBariatric Surgery – A Systematic Review and Meta-analysis

Buchwald H. et al.JAMA. 2004; 292(14):1724-37

Buchwald, JAMA, 2004

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%

.

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

Mortality Rate After Bariatric Surgery

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

Survival After Bariatric Surgery by Age Group

Klein, NEJM 2004

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

The Magic Formula