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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.

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Presentation on theme: "CLINICAL DILEMMAS IN OBESITY MANAGEMENT Robert B. Baron MD MS Professor and Associate Dean UCSF School of Medicine Declaration of full disclosure: No conflict."— Presentation transcript:

1 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

2 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?

3 CLASSIFICATION OF OVERWEIGHT AND OBESITY BY BMI Obesity ClassBMI (kg/m 2 ) Underweight <18.5 Normal18.5 – 24.9 Overweight25.0 – 29.9 Obesity I30.0 – 34.9 II35.0 – 39.9 Extreme Obesity III >40

4 Flegal, JAMA, 2005 BMI AND MORTALITY: Overall Combined NHANES I, II, and III data set BMI y y 70 y < < to < to <

5 An Office-Based Approach Make the diagnosis (and communicate it) Assess readiness for change Prescribe diet and exercise Consider medications and surgery

6 HEALTH PROFESSIONAL ADVICE AND WEIGHT LOSS 12,835 adults, BMI over 30 kg/m 2, 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 )

7 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

8 NCEP, JAMA 2001 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

9 GOALS OF MANAGEMENT Be as fit as possible at current weight Prevent further weight gain If successful at 1 and 2, begin weight loss

10 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.

11 DIET THERAPY 48 RCTS Average weight loss 8% over 3-12 months

12 Anderson, Am J Clin Nutr, 2001 VLCDs vs LCDs: Meta-analysis of 29 U.S. Studies Weight loss studies with > two year f/u 13 VLCDs, 14 LCDs Mostly observational studies (few RCTs) Weight loss (as % of initial weight): 1y2y3y4y5y LCDs VLCDs

13 Dansinger, JAMA 2005 COMPARISON OF ATKINS, ORNISH, WEIGHT WATCHERS, AND ZONE Intention to treat at 1 year Atkins Ornish WWZone Wt Loss (kg) Completers (%) Completers at 1 year Atkins Ornish WWZone Wt Loss (kg) patients, randomly assigned

14 Dansinger, JAMA, 2005 COMPARISON OF ATKINS, ORNISH, WEIGHT WATCHERS, AND ZONE

15 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

16 Wei, JAMA 1999 FITNESS AND MORTALITY Aerobics Center Longitudinal Study CV death (RR) normal overweight obese Fit Not fit Total death (RR) normal overweight obese Fit Not fit ,714 men, 44 years old, 14 year observational study

17 Hu FB, NEJM 2004 FITNESS AND OBESITY Nurses Health Study Total death (RR) normal overweight Active Not active ,564 women, 24 year observational study

18 Wing and Hill, Ann Rev Nutr, 2001 SUCCESSFUL WEIGHT LOSS MAINTENANCE <3000 subjects in National Weight Control Registry: 30-lb weight loss for 1-year

19 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

20 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.

21 Glazer, Arch Int Med 2001 LONG TERM PHARMACOTHERAPY OF OBESITY Review of all RCTs more than 36 weeks published since 1960 Weight loss in excess of placebo: % of initial kgs Phen-fen11.0%9.6 kg Phentermine8.1%7.9 kg Sibutramine5.0%4.3 kg Orlistat3.4%3.4 kg Dexfenfluramine3.0%2.5 Kg Fluoxetine-0.4%-0.4 kg Diethyproprion-1.5%-1.5 kg

22 Wadden, T. A. et al. N Engl J Med 2005;353: SIBUTRAMINE ALONE AND WITH LIFESTYLE MODIFICATION

23 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

24 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

25 RIMONABANT (Acomplia) 1,507 severely obese people, Europe, 2-years (2005) rimonabant7.3 kg loss placebo2.5 kg loss 3,040 obese people, US, 2-years (2004) rimonabant 7.6 kg loss placebo2.3 kg loss

26 Change From Baseline, kg Placebo 5 mg of Rimonabant 20 mg of Rimonabant Weeks Year 1 Body Weight

27 Change From Baseline, kg Placebo/Placebo 20 mg rimonabant/Placebo 20 mg rimonabant/20 mg Weeks Year 2 Body Weight 8468

28 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

29 PRINCIPLES OF DRUG THERAPY NIH: BMI > 30 kg/m 2 or 27 kg/m 2 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

30 Wouldnt It Be Easier Just To Have Surgery?

31 No. of Procedures Year National Trends in Annual Numbers of Bariatric Procedures, of Bariatric Procedures, Data based on nationwide inpatient sample Projection based on preliminary data from 12 states for 2003 Error bars indicate 95% confidence intervals

32 Whos 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

33 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)

34 Restrictive Procedures VBG Adjustable Gastric Banding Roux-en-Y GB

35 Buchwald, JAMA, 2004 BARIATRIC SURGERY META-ANALYSIS Review of bariatric surgery (136 studies), , 22,092 patients weight loss (kgs) BMI decrease % excess weight loss Total Gastric Banding Gastric Bypass Gastroplasty Biliopancreatic diversion or duodenal switch

36 Resolution of Comorbidities

37 Buchwald, JAMA, 2004 BARIATRIC SURGERY META-ANALYSIS Review of bariatric surgery (136 studies), 22,092 patients Operative Mortality Gastric Banding0.1% Gastric Bypass0.5% Gastroplasty0.1% Biliopancreatic diversion or duodenal switch1.1%

38 . Flum, D. R. et al. JAMA 2005;294: Mortality Rate After Bariatric Surgery

39 Flum, D. R. et al. JAMA 2005;294: Survival After Bariatric Surgery by Age Group

40 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

41 The Magic Formula


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