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 Class BMI (kg/m2)
Underweight <18.5
Normal – 24.9
Overweight – 29.9
Obesity I – 34.9
II – 39.9
Extreme Obesity III >40

4. BMI AND MORTALITY: Overall
Combined NHANES I, II, and III data set
BMI y y ≥70 y
<
18.5-<
25 to <
30 to < ≥
Flegal, JAMA, 2005

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/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 )

7. 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

8. 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

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 RCT’S
Average weight loss 8% over 3-12 months

12. 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
VLCDs
Anderson, Am J Clin Nutr, 2001

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

14. 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

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. FITNESS AND MORTALITY Aerobics Center Longitudinal Study
25,714 men, 44 years old, 14 year observational study
CV death (RR)
normal overweight obese
Fit
Not fit
Total death (RR)
normal overweight obese
Fit
Not fit
Wei, JAMA 1999

17. FITNESS AND OBESITY Nurses Health Study
Total death (RR)
normal overweight
Active
Not active
116,564 women, 24 year observational study
Hu FB, NEJM 2004

18. 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

19. 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

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. “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% kg
Phentermine 8.1% kg
Sibutramine 5.0% kg
Orlistat 3.4% kg
Dexfenfluramine 3.0% Kg
Fluoxetine -0.4% kg
Diethyproprion -1.5% kg
Glazer, Arch Int Med 2001

22. SIBUTRAMINE ALONE AND WITH LIFESTYLE MODIFICATION
Figure 2. Mean ({+/-}SE) Weight Loss in the Four Groups, as Determined by an Intention-to-Treat Analysis (Panel A) and a Last-Observation-Carried-Forward Analysis (Panel B). Subjects who received combined therapy lost significantly more weight at all times than subjects in the other three groups. Subjects treated with lifestyle modification alone and those treated with sibutramine plus brief therapy lost significantly more weight at week 18 than those who received sibutramine alone, with no other significant differences at any other time. Panel B shows that a last-observation-carried-forward analysis yielded the same statistical conclusions.
Wadden, T. A. et al. N Engl J Med 2005;353:

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
Topiramate: weak carbonic anhydrase inhibitor; modulates the GABA receptors – approved as an anti-epileptic drug;
Unclear mechanism that contributes to weight loss effects.

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
Topiramate: weak carbonic anhydrase inhibitor; modulates the GABA receptors – approved as an anti-epileptic drug;
Unclear mechanism that contributes to weight loss effects.

25. 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 kg loss
placebo 2.3 kg loss

26. Change From Baseline, kg
Year 1 Body Weight
Placebo
5 mg of Rimonabant
20 mg of Rimonabant
Change From Baseline, kg 12 24 36 52
Weeks

27. Change From Baseline, kg
Year 2 Body Weight
Placebo/Placebo
20 mg rimonabant/Placebo
20 mg rimonabant/20 mg
Change From Baseline, kg 52 60 68 76 84 92
104
Weeks

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/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

30. Wouldn’t It Be Easier Just To Have Surgery?

31. 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
No. of Procedures
1998
1999
2000
2001
2002
2003
Year
Error bars indicate 95% confidence intervals

32. 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

33. Types of Surgery Restrictive Malabsorptive
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 Adjustable Gastric Banding
VBG
Adjustable Gastric Banding
Roux-en-Y GB

35. 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
Buchwald, JAMA, 2004

36. Resolution of Comorbidities

37. BARIATRIC SURGERY META-ANALYSIS
Review of bariatric surgery (136 studies), 22,092 patients
Operative Mortality
Gastric Banding 0.1%
Gastric Bypass 0.5%
Gastroplasty %
Biliopancreatic diversion
or duodenal switch 1.1%
Buchwald, JAMA, 2004

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

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

40. 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

41. The Magic Formula