Obesity Continuum of Care: Behavior Modification Through Pharmacotherapy and Surgery

1. Speaker notes included in notes section below Obesity Continuum of Care: Behavior Modification Through Pharmacotherapy and Surgery

2. Obesity Treatment Guidelines www.nhlbi.nih.gov www.naaso.org

3. Obesity Treatment Recommendations

4. Classification of Overweight and Obesity by BMI, Waist Circumference and Associated Disease Risks • Additional risks: • Large waist circumference (men > 40 in; women > 35 in) • Poor aerobic fitness • Specific races and ethnic groups • Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in • Adults—The Evidence Report. Obes Res 1998;6(suppl 2).

5. Metabolic Syndrome: NCEP ATP III compared to IDF * requires presence of 3 or more criteria ** requires central adiposity and presence of 2 more criteria

6. Metabolic Risk Identified by “Hypertriglyceridemic Waist” waist TG waist TG waist TG waist TG Insulin Resistance (HOMA) Waist = 95 cm M 88 cm F TG = 128 mg/dl Men Women Men Women Age 55-74 Age 18-34 • Cutpoints are lower with increased risk • Kahn and Valdez. AJCN 2003;78:928-34

7. BMI  40 35 30 25 Surgery Pharmacotherapy Lifestyle Modification Diet Physical Activity Obesity Treatment Pyramid

8. A Guide to Selecting Treatment The Practical Guide. 2000.

9. Assessing Readiness • Why now? • What changes will you have to make? • What will change if you lose weight? • What do others think about your weight? • What else is going on in your life?

10. Assessing Readiness • We are not good at predicting outcomes. • Patients ultimately make the decision. • Providers assess costs/benefits in a variety of contexts.

11. 5 Steps to Behavior Change 1. Have patient identify specific goals • Activity (i.e., one specific goal for exercise) • Intake (i.e., one specific goal for diet) 2. Identify when, where, and how behaviors will be performed 3. Have patient keep record of behavior change (i.e., diet and activity diaries) 4. Follow-up progress at next treatment visit 5. Congratulate patient on successes; do not criticize shortcomings Wadden & Foster. Medical Clinics of North America, 2000.

12. Patient’s Dietary Intake and Trends • 70% of American adults say they are eating “pretty much whatever they want”1 • Caloric intake has increased by 300 calories per person per day from 1985-20001 • Refined grains accounted for 46% of increase • Added fats: 24% of increase • Added sugars: 23% of increase • Fruits and vegetables: 8% of increase • Meat and dairy declined • Americans will spend 47% of their food dollar in restaurants in 20052 1 Putnam J et al. USDA FoodReview, Vol 25 (3); 2002. 2www.restaurant.org/pressroom/pressrelease.cfm?ID=979, obtained 3/14/05.

13. New Food Pyramid &Dietary Guidelines www.mypyramid.gov and www.healthierus.gov/dietaryguidelines

14. MyPyramid.gov • Website designed for easy patient use • MyPyramid plan provides estimates of amounts of food by a patients entering their age, sex and activity level • Assessment of food intake and physical activity levels available on MyPyramid Tracker • Other advice and tips available at “Inside MyPyramid”

15. Dietary Factors to Address Fat Fruits and Vegetables Eating Out Portion Size Fiber Caloric Beverages

16. One “Diet” Does Not Fit All Low Calorie Diet Low Fat Diet Low Carb Diet

17. Comparison of Popular Diets Mean Changes in Weight and Cardiac Risk at 12 Months Dansinger, et al. JAMA 2005;293:43-53.

18. Meal Replacements Promote Long and Short term Weight Loss *1200–1500 kcal/d diet prescription A: conventional foods B: meal and snack replacement for 1 meal, 1 snack Fletchner-Mors et al. Obes Res 2000;8:399.

19. “Do not judge the impact of physical activity by weight loss” Dr. Steve Blair - Cooper Institute September 20, 2004

20. Why the difference in impact for physical activity between weight loss and weight loss maintenance?

21. Differences Between Weight Loss and Weight Loss Maintenance

22. How Much is Enough?Current Physical Activity Recommendations • Minimal public health recommendations to improve health related outcomes • 30 min moderate activity most days of the week (150 minutes/week) • CDC - Centers for Disease Control • ACSM - American College of Sports Medicine • SG - Surgeon General • Maximize weight loss and prevent weight regain • 45-60 minutes/day • IOM - Institutes of Medicine • 60-90 minutes/day • IASO - International Assoc for Study of Obesity • 60 minutes/day (300 minutes/week) • ACSM - American College Sports Medicine • Preventing general weight gain • Unclear

23. Principles of Obesity Medication Use • Lifestyle interventions are the foundation of medicating for obesity • The benefits of modest (5 - 10% of body weight) should be emphasized • The behavioral approach should be implemented with knowledge of the medication’s mechanism of action • Orlistat with 30% fat diet • Sibutramine with meal plan that takes advantage of its satiety promotion • Obesity medications do not cure obesity, just as antihypertensives do not cure hypertension • Not all patients respond to a weight loss medication. • If the drug’s use is not associated with weight loss within four weeks, it should be stopped • Medications work as long as they are used • Weight gain occurs on stopping medications, although there is some evidence in support of efficacy of intermittent medication

24. Antiobesity Drugs Approved for Long-Term Use: How They Work

25. Sibutramine Key Facts • Multiple large clinical trials demonstrating: • Dose-related weight loss occurs for 6 months • Amount of weight loss related to intensity of behavioral approach • Efficacy in weight loss maintenance demonstrated ≥ 2 years • Weight loss produces benefits in lipids, body composition and is associated with mean blood pressure decrease • Trials in patients with hypertension and diabetes • Favorable side effect profile: • No abuse potential • No valvuloplasty, no PPH • Cautions • Blood pressure should be monitored • Should not use with MAOIs, erythromycin, ketoconazole

26. Sibutramine + Group Sessions + Meal Replacements Sibutramine + Group Sessions Sibutramine The Amount of Weight Loss with Sibutramine Is Related to the Intensity of the Behavioral Intervention* * Weight loss at 6 months Wadden TA et al. Arch Intern Med 2001;161:218-227.

27. STORM: 77% (ITT) Achieved > 5% Weight Loss at Six Months Weight Loss Weight Maintenance 230 Placebo 225 220 215 Body Weight (lb) 210 205 200 Sibutramine 195 0 2 4 6 8 10 12 14 16 18 20 22 24 Month *Same diet, exercise for sibutramine, placebo; P  0.001, sibutramine vs placebo for weight maintenance James WPT et al. Lancet. 2000;356:2119.

28. Weight Loss with Sibutramine Is Associated with Improvement in Waist Circumference (STORM data) 44 43 Placebo 42 Waist Circumference (in.) 41 40 Sibutramine 39 38 0 2 4 6 8 10 12 14 16 18 20 22 24 Month NB: Same diet and exercise for both sibutramine and placebo James WPT et al. Lancet. 2000;356:2119.

29. Weight Loss with Sibutramine Is Associated with Improvements in Lipids(STORM Data) Triglycerides VLDL-Cholesterol 5 5 0 0 Placebo Placebo –5 –5 % Change –10 –10 % Change ‡ §  * * †    –15 * –15    Sibutramine     Sibutramine    –20 –20  –25 –25 24 0 6 12 18 0 6 12 18 24 Month Assessed Month Assessed HDL-Cholesterol 25 * *   Sibutramine 20    15 % Change Weight loss = months 1–6; Weight maintenance = months 7–24; *P < 0.001; †P = 0.002; ‡P = 0.005; §P = 0.001 vs placebo Placebo 10  5  0 Adapted with permission from James WPT et al. Lancet. 2000;356:2119. 0 6 12 18 24 Month Assessed

30. Dose Related Effects of Sibutramineon Systolic Blood Pressure (SBP) Sibutramine 10 mg n=1318 Sibutramine 15 mg n=1924 Sibutramine 20 mg n=1126 Sibutramine 30 mg n=128 Placebo n=1944 10 8 6 +3.8 * Change in SBP (mmHg) 4 +2.6 * +1.0 * 2 -0.1 -0.1 0 -1 * p < 0.05 compared to placebo **The shaded area represents doses not approved for use by the FDA. Data on file, Abbott Laboratories.

31. Sibutramine: Effect on Blood Pressure • Mean BP changes in recommended dose range is ~ 1 mm Hg increase • A few, < 5%, have unacceptable blood pressure increases while on sibutramine • Significant weight loss, > 5%, is associated with mean BP decrease on sibutramine • BP effects of sibutramine are blocked by beta blockers1 • BP effects of sibutramine are blocked by exercise program2 • In addition to peripheral effects, sibutramine may have central “clonidine-like” sympatholytic effects1 • BP changes are usually seen in the first four weeks of therapy (need to add reference for this) • Birkenfeld AL et al. Circulation 2002;106: 2459-2465. • Berube-Parent S et al. IJO 2001;25: 1144-1153.

32. Tips for Managing Patients on Sibutramine • Start at 10 mg once daily • Prescribe a sensible diet • Meal replacements for two meals and two snacks + one sensible meal per day • Portion controlled diet with at least three meals per day • Follow-up: • 4 pounds weight loss in first 4 weeks helps predict success • Monitor blood pressure. Use clinical judgement about continuing • Increase dose to increase weight loss, provided BP is well controlled. Decrease dose or discontinue for BP concerns • Stay within recommended dose range of 5 to 15 mg • Encourage long term use

33. Orlistat: Key Facts • Multiple large clinical trials demonstrating • Weight loss occurs for 6 months • Efficacy in weight loss maintenance demonstrated ≥ 4 years • Weight loss produces benefits in glycemic control, lipids, waist circumference, BP • Trials in persons with diabetes and hypertension • Independent action on LDL cholesterol • Favorable side effect profile • No abuse potential • No valvulopathy, no PPH • Cautions • Vitamin supplement required for long term use • May interfere with cyclosporin absorption • Likely to be available over the counter in 2006

34. Orlistat + lifestyle(n=853) Placebo + lifestyle(n=557) Weight change (kg) 0 -3 -4.1 kg -6 -6.9 kg -9 -12 0 52 104 156 208 Week Effect of Long-Term Treatment With Orlistat (The XENDOS Study) Completers Data p < 0.001 vs placebo Torgerson JS et al, Diabetes Care 2004; 27(1): 155-61.

35. Effect of Orlistat on Weight and Body Composition in Obese Adolescents • 54-week multi-center, double-blind, placebo-controlled study • 539 obese adolescents, aged 12-16 (357 receiving orlistat 120 mg three times daily, 182 receiving placebo) • Baseline BMI – 2 units > than US weighted mean for the 95th percentile based on age and gender • Patients placed on reduced-calorie diet and behavior modification program • 65% of patients in each treatment group completed study Chanoine JP, JAMA 2005 Jun 15;293(23):2873-83.

36. Obese Adolescents with ≥ 5% and ≥ 10% Decrease in BMI and Body Weight after 1-Year Treatment* * Treatment designates orlistat 120 mg three times a day plus diet or placebo plus diet. † Last observation carried forward. Chanoine JP, JAMA 2005 Jun 15;293(23):2873-83.

37. Tips for Managing Patients on Orlistat • Discuss potential bowel effects and mechanism with patient • Start at 120 mg before each meal • Prescribe a moderate fat diet • Caution patients about high fat meal or snack • Metamucil has been shown to reduce bowel effects • For long term use, prescribe a multivitamin • Orlistat can interfere with cyclosporin absorption • Encourage long term use.

38. Obesity Pharmacotherapy Summary • Medications approved for long-term use • sibutramine (Meridia) • orlistat (Xenical) • Medications approved for short-term use • phentermine • others rarely used: mazindol, diethylpropion • Medications for use in special patients • the depressed obese patient – bupropion (Wellbutrin) and venlafaxine (Effexor) • type 2 diabetes – metformin , pramlintide (Symlin), exendin-4 (Exenatide) • patients with neuropsychiatric problems – topiramate (Topamax) and zonisamide (Zonegran) • Medications in development • rimonabant (Acomplia)

39. Bariatric Surgery: Recommendations for Patient Selection • Between ages 18 and 50 • Stable preoperative weight for 3-5 years • Smoking cessation for at least 6 weeks • Those with psychiatric history require careful assessment • Tests to predict success of surgery: • Personality factors • Eating habits • Motivation Grace DM. Gastroenterol Clin North Am. 1987;16:399.

40. Recommendations for Patient Selection- NIH Guidelines • Motivated subjects with acceptable surgical risks with • BMI ≥ 40 • OR • BMI ≥ 35 with comorbid conditions Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults—The Evidence Report. Obes Res 1998;6(suppl 2).

41. Update: Bariatric Surgery Currently Popular Procedures Gastric Bypass LapBandTM Restriction Malabsorption

42. Bariatric Surgery: Mechanisms • Operations dramatically restrict gastric size, reducing nutritional intake • Some types of surgery decrease the absorption efficiency of nutrients • Roux-en-Y gastric bypass • Biliopancreatic diversion (BPD) • Malabsorption procedures create a greater risk for nutritional deficiencies

43. Iron deficiency Vitamin B12 deficiency Folic Acid deficiency Dehydration Vitamin A deficiency Electrolyte deficiency Protein deficiency Hyperparathyroidism Follow up of nutritional and metabolic problems after bariatric surgery Nausea Vomiting Abdominal pain Constipation Marginal ulceration Gallstones Bleeding ulcer Obstruction of the stomach outlet Bariatric Surgery: Side Effects & Complications 1 in 200-300 patients in the US die from bariatric surgery Fujioka K, Diabetes Care 28:481-484,2005. Shikora SA. Nutrition in Clinical Practice. 2000;15:13. www.mayoclinic.com. Surgery for obesity: What is it and is it for you?. Accessed February 15, 2005.

44. Bariatric Surgery: Mortality • Roux-en-Y gastric bypass surgery appears to have a mortality rate ranging from 0.3% (95% CI, 0.2% to 0.4%) from case series data to 1.0% (95% CI, 0.5% to 1.9%) in controlled trials. • Adjustable gastric banding appears to have an early mortality rate of 0.4% (95% CI, 0.01% to 2.1%) for controlled trials and 0.02% (95% CI, 0.9% to 0.78%) for case series data. • No statistically significant difference in mortality seen between procedures. Snow V.  Ann Int Med 2005;142:525-531.

45. Surgical Volume and Mortality • Surgical technique involved a significant learning curve • Centers that perform more procedures have a lower mortality rate • One study (Flum D, et al) found surgeons who performed fewer than 20 procedures had patient mortality rates of 5%, as compared with a near 0% mortality for surgeons who had performed 250 or more procedures. Snow V.  Ann Int Med 2005;142:525-531.