The Treatment of Obesity: Diet and Medication

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1 The Treatment of Obesity: Diet and Medication Doina Kulick, M.D., M.S., F.A.C.P. Associate Professor of Medicine University of Nevada Reno School of Medicine Financial Disclosure: None 2013 Washoe County Obesity Forum September 19, 2013 Stack the Odds of Health in Your Favor 1 Learning Objectives The learner should be able to improve practice, and evaluate evidence by: Learning about the trends in obesity and the their relationship with food environment and physical activity Understanding the principles and the effect of lifestyle therapy on body weight management Learning the effectiveness of different types of diet on body weight management Understanding the role of physical activity in weight loss and weight maintenance Becoming familiar with the drugs approved for weight loss, their indications, usage and efficiency. 2 1

2 Obesity is a complex, multifactorial, chronic disease that develops from the interaction of the genotype and the environment and consists in excessive accumulation of fat tissue. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults The NIH, National Heart, Lung and Blood Institute, , Sept Overweight and Obesity in USA 4 2

devices Television/computer WEIGHT GAIN CALORIES IN Portion size High energy density High glycemic index Soft

3 5 The Energy Imbalance CALORIES OUT Sedentary workplaces Sedentary schools Activity unfriendly community design Automobiles Drive through conveniences Elevators/escalators Remote controls Sedentary entertainment Labor saving devices Television/computer WEIGHT GAIN CALORIES IN Portion size High energy density High glycemic index Soft drinks/ junk food In schools Added sugar Easy food access Low cost Variety Convenience Great taste Ads/marketing 6 3

US Daily Per Capita Food Supply Adapted from Harnack LJ, et al. Am J Clin Nutr 2000;71:1478 84.

4 US Daily Per Capita Food Supply Adapted from Harnack LJ, et al. Am J Clin Nutr 2000;71: Introduction of New, Larger Portion Sizes, Young LR, Nestle M. Am J Public Health 2002;92:

5 40 Years Ago COFFEE Today Coffee (with whole milk and sugar) Mocha Coffee (with steamed whole milk and mocha syrup) 45 calories 8 ounces 350 calories 16 ounces Calorie Difference: 305 calories MUFFIN 40 Years Ago Today 210 calories 1.5 ounces 500 calories 4 ounces Calorie Difference: 290 calories 10 5

6 CHEESEBURGER 40 Years Ago Today 333 calories 590 calories Calorie Difference: 257 calories 11 SODA 40 Years Ago Today 85 Calories 6.5 ounces 250 Calories 20 ounces Calorie Difference: 165 Calories 12 6

7 40 years ago Today 673 Cal Cal. Portion Size Affects Consumption Macaroni and Cheese Study Entrée macaroni & cheese served for lunch in randomly presented portion sizes, intake measured 500 g served consumed 335 g (2286 kj) 650 g served consumed 374 g (2553 kj) 750 g served consumed 400 g (2728 kj) 1000 g served consumed 434 g (2962 kj) Largest portion size resulted in 30% more food and energy consumed than the smallest portion Reported similar ratings of hunger and fullness despite the intake differences After the study, only 45% of participants reported noticing differences in portion sizes served Rolls BJ et al Am J Clin Nutr 2002;76:

8 Total Energy Intake* Age 20 74, by Sex and Year: NHANES kcal Year Intake all foods & beverages Health, US Daily Occupational Caloric Expenditure Church TS et al. PLoS

9 Physical activity: Travel US average= 73 mins/day of driving 25% of all trips made are one mile or less, but most of these short trips (76%) are made by car School trips one mile or less: only 31% are made by walking. In the US, 6% of all trips are by walking/biking. In contrast, Italy (54%), Sweden (49%) Percent Percent Automobile Trips Walk and Bike Trips NIH Guide to Selecting Obesity Treatment Treatment Lifestyle Therapy* BMI Category > Medication with comorbid Surgery with comorbid + *dietary therapy, physical activity, and behavior therapy NHLBI and NIDDKD. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: evidence report. Obes Res. 1998;6(suppl 2):51S 210S. 18 9

10 Lifestyle Therapy It is the cornerstone of obesity treatment and includes: 1. Diet 2. Increased physical activity 3. Behavior modification Dietary Therapy The NHLBI Guidelines recommend initiating dietary management with a low calorie diet to produce a calorie deficit of 500 to 1,000 kcal/day. This type of calories reduction typically results in a loss of 1 to 2 lb/week and has been shown to reduce total body weight by an average of 8% over 6 to 12 months 20 10

11 What is the best diet for weight loss? 21 Type of Diets Based on Macronutrient Composition Used in Weight Loss Balanced low calorie diets (55% C/15% P/30% F) Low fat diets (20 25% F ) Low carbohydrate diets (~40% C) High protein diets(25 35% P) The United States (US) Dietary Guidelines report as acceptable the following range of macronutrients in the diet: 45 to 65 % from carbohydrates (C) 10 to 35 % from protein (P) 20 to 35 % from fat (F) 22 11

12 Weight loss with conventional versus low carbohydrate diet Stern L, et al. Ann Intern Med 2004; 140: POUNDS LOST: Weight Loss (ITT) 24 12

13 Meta-analysis for changes in body weight (kg) in randomized controlled trials that compared high-protein, low-fat diets with isocalorically prescribed standard-protein, low-fat, energy-restricted diets. Wycherley T P et al. Am J Clin Nutr 2012;96: Summary of Meta Analyses on Diet Comparison Studies 1. Bueno et al 2013 (13 studies) Low carb ketogenic diet vs Low fat diet Weight loss difference: 2 lbs (low carb) 2. Wycherley et al 2012 (24 studies) High protein/low fat vs Standard protein/low fat Weight loss difference: 1.7 lbs (high protein/low fat) 3. Hu et al 2012 (23 studies) Low carb vs. Low fat Weight loss difference: NONE 4. Ajala et al 2013 (20 studies) Low carb, Vegetarian, Vegan, Low GI, Mediterranean, High protein vs Low Fat Weight loss difference: Low carb > low fat by 1.5 lbs. Mediterranean > low fat by 4 lbs All other diets no different from low fat 5. Schwingshackl et al 2013 (15 studies) High protein vs Low Protein Weight Loss Difference: NONE. Pagoto, SL. JAMA, 2013, 310:7;

14 POUNDS LOST: Weight Change and Attendance Attendance at group sessions strongly predicted weight loss. Behavioral factors rather than macronutrient metabolism are main influences on weight loss. 27 The Bottom Line Diets result in clinically meaningful weight loss regardless of which macronutrient they emphasize Behavioral adherence is much more important than diet composition: the best approach is to counsel patients to choose a dietary plan they find easiest to adhere to in the long term. Do not us diets with extreme food composition (fad diets) Patients should develop an appropriate physical activity program and learn new behaviors to promote long term adherence

Meal Replacements (MR) MR refers to a calorie controlled, prepackaged product in the form of a bar, beverage (ready to drink or powder), or entree that replaces a regular meal.

15 Meal Replacements (MR) MR refers to a calorie controlled, prepackaged product in the form of a bar, beverage (ready to drink or powder), or entree that replaces a regular meal. MR products usually provide 150 to 250 calories per serving, and are fortified with vitamins and minerals They are used to replace 1 2 regular meals/day, usually in conjunction with fruits and vegetable (partial MR diets), and are used during weight loss and weight maintenance phase. Total MR diets (all meals as MR +/ fruits and vegetables) are not recommended for long term use, due to potential nutritional deficiency Keogh JB, Obes Rev Aug;6(3): Meal Replacements Enhance the Initial and Long term Weight Loss 30 15

16 Percentage reduction in initial weight at 1 year based on quartile of meal replacement products (MR) used in the Look Ahead Study Wadden TA,Obesity 2009;17:

Very low calorie diets (less than 800 kcal/day) Produce greater initial weight loss than lowcalorie diets.

Not recommended for pregnant or breastfeeding women Not appropriate for children or adolescents Not

Physical Activity To achieve a 300 calories negative energy balance: Reduce intake by: OR Increase activity

17 Very low calorie diets (less than 800 kcal/day) Produce greater initial weight loss than lowcalorie diets. However, long term (>1 year) weight loss is not different from an low calorie diets Need physician supervision Not recommended for pregnant or breastfeeding women Not appropriate for children or adolescents Not recommended for older individuals Tsai AG, Wadden TA. Obesity (Silver Spring). 2006;14(8): Physical Activity To achieve a 300 calories negative energy balance: Reduce intake by: OR Increase activity by: Eliminating 2 oz potato chips Running 3 miles in 30 min Substituting 2 diet sodas for 2 regular sodas Bicycling 8 miles in 30 min 34 17

2.Physical Activity: Exercise as a single treatment: weight loss of 0.

of weight loss: improve body composition and insulin resistance decrease overall mortality It is the

be single session or intermittent Start with walking 30 minutes 3 days/week Goal: 60 90 min of low/mod activity

Role of physical activity and exercise in obese adults, UptoDate, Aug. 2013 35 3.

18 2.Physical Activity: Exercise as a single treatment: weight loss of 0.2 lb/week Exercise added to diet: has little additional effect upon weight, BUT Has health benefits independent of weight loss: improve body composition and insulin resistance decrease overall mortality It is the intervention most likely to promote long term maintenance of weight loss Start slowly and increase gradually Can be single session or intermittent Start with walking 30 minutes 3 days/week Goal: min of low/mod activity every day Encourage increased lifestyle activities Aids: Pedometer goal 10,000 steps/day Bray G. Role of physical activity and exercise in obese adults, UptoDate, Aug Behavioral Therapy for Obesity Self Monitoring Problem Solving Cognitive Restructuring Contingency Management Social Support Stress Management Stimulus Control Wadden and Foster. Med Clin North Am 2000:84:

19 Sustained Weight Loss Can Be Achieved with Lifestyle Therapy Weight Loss (kg) Active Treatment Years No Active Treatment Women Men Björvell and Rössner. Int J Obes Relat Metab Disord ;16: Cardinal Behaviors of Successful Long term Weight Management National Weight Control Registry Data 10,000 adults who were able to lose 30 pounds or more and maintain their losses for at least one year by changing their lifestyles. Participants lost an average of 66 lbs and kept it off for an average of 5.5 years 45% of them lost the weight on their own and the other 55% lost weight with the help of some type of program 98% of participants report that they modified their food intake in some way to lose weight 94% increased their physical activity, with the most frequently reported form of activity being walking. 90% exercise, on average, about 1 hour per day 62% watch less than 10 hours of TV per week 78% eat breakfast every day 38 accessed Aug. 10,

20 Pharmacotherapy for Weight Loss 39 Obesity drugs are approved for use in: Patients with a BMI of 30 or above with no concomitant risk factors or diseases, OR Patients with a BMI of 27 or above with concomitant type 2 diabetes, hypertension, dyslipidemia, coronary heart disease, sleep apnea AND Who have not lost the recommended 1lb/week after several months on lifestyle therapy alone 20

21 FDA Approved Obesity Drugs: For long term use (>6 mo) Orlistat (Xenical), Lorcaserin (Belviq), (IV) Phentermine /Topiramate (Qsymia ), (IV) For short term use (<3 mo) Phentermine (Adipex), (IV) Diethylpropion (Tenuate), (IV) Phendimetrazine tartrate, (III) Benzphetamine (Didrex), (III) 41 Phentermine FDA approved in 1959 for short term use (<3 mo.) Appetite suppressant, noradrenergic agent The most commonly prescribed of the anorectic agents (withdrawn in Europe) Dosing: 15 to 37.5 mg before breakfast Contraindications: advanced arteriosclerosis, cardiovascular disease, HTN, hyperthyroidism, glaucoma, agitation, and drug or alcohol abuse Side effects: central nervous system stimulation, impotence, arrhythmias, hypertension, psychosis Costs $20 25/month 42 21

Effect of Continuous and Intermittent Phentermine Therapy on Body Weight Weight Loss (lbs) Continuous Placebo Continuous Phentermine 0 Alternate Phentermine and Placebo 4 8 12 16 20 24 28 32 Time

22 Effect of Continuous and Intermittent Phentermine Therapy on Body Weight Weight Loss (lbs) Continuous Placebo Continuous Phentermine 0 Alternate Phentermine and Placebo Time (weeks) 36 Munro JF et al. Brit Med J 1:352, Orlistat (Xenical) FDA approved in 1999 for long term treatment of obesity Only FDA approved drug for the management of obese adolescents age 12 to 16 years (Dec. 2003) Costs $250/month Orlistat Package Insert,

23 Orlistat Prevents Fat Digestion and Absorption by Binding to Gastrointestinal Lipases Intestinal Lumen Mucosal Cell Orlistat TG MG FA Bile Acids Micelle TG=triglyceride; MG=monoglyceride; FA=fatty acid. 45 Orlistat (Xenical) Dose: 120 mg TID within 1 hr. of food intake A lower dose (60 mg) over the counter version (Alli) Contraindications: cholestasis, malabsorption syndrome. Caution should be used with patients with IBS, hyperoxaluria and Ca oxalate nephrolithiasis Interactions: decreased absorption of the fat soluble vitamins A, D, E, and K. A multivitamin with minerals should be taken 2 hours before or after orlistat Orlistat Package Insert,

24 Effect of Long term Treatment With Orlistat (The XENDOS Study): Torgerson JS et al. Diabetes Care. 2004;27(1): Lorcaserin (Belviq) A selective agonist of the brain serotonin 2C receptor. The selectivity for central serotonin 2C receptors is approximately 15 and 100 times over that for serotonin receptors 2A and 2B respectively. Decreases appetite 10 mg twice daily PO Approved by the FDA in June 2012 (vote 18:4) Costs $220/month 48 24

Categorical Weight Change Over With Lorcaserin Therapy BLOOM Smith SR, Weissman NJ, Anderson CM, Sanchez M, Chuang E, Stubbe S, Bays H, Shanahan WR 2010 Multicenter, placebo controlled trial of

25 Categorical Weight Change Over With Lorcaserin Therapy BLOOM Smith SR, Weissman NJ, Anderson CM, Sanchez M, Chuang E, Stubbe S, Bays H, Shanahan WR 2010 Multicenter, placebo controlled trial of lorcaserin for weight management. N Engl J Med 363: Categorical Weight Change Over With Lorcaserin Therapy BLOOM 47.5% 20.3% 22.6% 7.7% Smith SR, Weissman NJ, Anderson CM, Sanchez M, Chuang E, Stubbe S, Bays H, Shanahan WR 2010 Multicenter, placebo controlled trial of lorcaserin for weight management. N Engl J Med :

26 Lorcaserin (Belviq) The efficacy of lorcaserin appears similar to that of orlistat (mean difference in weight loss between active and placebo treated groups approximately 4 kg) and perhaps slightly less than that of phentermine topiramate Lorcaserin should be discontinued if patients do not lose 5% of body weight in 12 weeks Adverse effects: headache, upper respiratory infections, nasopharyngitis, dizziness, and nausea. Echo studies showed no increased incidence of FDA defined cardiac valvulopathy, but the studies were not powered adequately for complete confidence because of a lower than expected event rate. 51 Phentermine/Topiramate (Qsymia) Phentermine induces central NE release decreasing appetite. Topiramate monotherapy ( mg/day) was approved in 1996 for the treatment of seizures and in 2004 for migraine prophylaxis (50 100mg/day) Topiramate has effect on sodium channels and GABA activated chloride channels, inhibits carbonic anhydrase isoenzymes, but the specific mechanism promoting weight loss is unclear. FDA approved phentermine/topiramate in July of 2012 (vote 20:2) 52 26

27 Phentermine/Topiramate (Qsymia) In combination the two drugs have shown greater weight reduction than either agent alone. Given once a day in escalating dose (3.75/23 mg,7.5/46 mg or 15/92 mg) If an individual does not lose 5 % of body weight after 12 weeks on the highest dose, phentermine/topiramate should be discontinued gradually, as abrupt withdrawal of topiramate can cause seizures 53 Effect of Phentermine/Topiramate ER on Weight Loss in Obese Adults After 1 Year CONQUER Gadde KM, et al. Lancet. 2011;377:

28 Effect of Phentermine/Topiramate ER on Weight Loss in Obese Adults After 1 Year CONQUER Gadde KM, et al. Lancet. 2011;377: Phentermine/Topiramate (Qsymia) Side effects: dry mouth, constipation, paraesthesia, depression, disturbance in attention. Increased risk of orofacial clefts in infants exposed to the combination drug during the first trimester of pregnancy Women of child bearing age should have a pregnancy test before starting this drug and monthly thereafter! Contraindications: hyperthyroidism, glaucoma, monoamine oxidase inhibitors intake within 14 days. Used cautiously in patients with a history: of renal stones (topiramate can produce renal stones), cardiovascular disease (hypertension or coronary heart disease) 56 28

29 Weight loss with various medications and dietary counseling Drug Length of trial Total weight loss NNT 5%WL 10%WL Phentermine 13 wks - 14 Lbs 2 3 Orlistat (Xenical) 1 year - 12 Lbs 5 9 Lorcaserin (Belviq) 1 year - 13 Lbs 5 8 Phen/Topiramate (Qsymia) 1 year - 22 Lbs 2 3 NNT=number needed to treat WL=weight loss N Engl J Med 2010 Jul 15;363(3):245, BMJ 2012; 344:d7771, Ann Intern Med 2011; 155:434, Diabetes Obes Metab 2010 Oct;12(10): The results of the weight loss clinical trial need to be interpreted cautiously because of very high rate (>35%) of patients discontinued the treatment! NNT (number needed to treat) represents the number of patients we need to treat with the drug in order to achieve 1 good outcome and incorporates the duration of treatment. Example: For Phen/Topiramate (Qsymia) they had to treat 5 patients for 1 year in order to have one of them lose 5% of their initial weight; and treat 8 patients for 1 year in order to have one of them lose 10% of their initial weight

30 Monitor the weight loss medication! Patients stared on medication should follow up in 2 4 weeks and than every 1 3 months for response to therapy and side effects If no response to therapy in 3 months (failed to lose at least 5% of initial body weight), drug should be discontinued Arch Intern Med 1998 Sep 28;158(17): Questions?

MEDICAL MANAGEMENT 101

MEDICAL MANAGEMENT 101 Christopher Still, DO, FACN, FACP Medical Director, Center for Nutrition & Weight Management Director, Geisinger Obesity Research Institute Geisinger Health Care System Your Weight