Cornerstones of Obesity Management: Disease Recognition, Patient Engagement, and Lifestyle Management

Transcription

1 Education partner, the Institute for Medical and Nursing Education, Inc. Generic Name Brand Name Generic Name Brand Name amitriptyline Elavil naltrexone ER/bupropion ER Contrave aripiprazole Abilify nefazodone Serzone atorvastatin Lipitor nortriptyline Pamelor benzphetamine Didrex olanzapine Zyprexa, Zydis bupropion Wellbutrin, Zyban orlistat Alli, Zenical carbamazepine Tegretol paroxetine Paxil clozapine Clozaril phendimetrazine Bontril diethylpropion Tenuate phenelzine Nardil doxazosin Cardura phentermine Adipex-P, Fastin doxepin Sinequan phentermine/topiramate ER Qsymia duloxetine Cymbalta propranolol Inderal felbamate Felbatol pregabalin Lyrica fluoxetine Prozac protriptyline Vivactil gabapentin Neurontin quetiapine Seroquel haloperidol Haldol risperidone Risperdal imipramine Tofranil sertraline Zoloft lamotrigine Lamictal thioridazine Mellaril liraglutide 3. mg Saxenda topiramate Topamax lorcaserin Belviq valproate Depacon mirtazapine Remeron vigabatrin Sabril metformin Glucophage, Glumetza ziprasidone Geodon Learning Objectives Summarize current recommendations for screening, assessment, and treatment goals in the management of adult obesity Develop individualized therapeutic regimens for adults with obesity, incorporating lifestyle management and adjunct therapies as appropriate, based on current treatment recommendations and recent evidence Utilize clinically validated approaches and tools to engage and support patients in the management of adult obesity as a chronic disease Cornerstones of Obesity Management: Disease Recognition, Patient Engagement, and Lifestyle Management Scott Urquhart, PA-C Past President American Society of Endocrine Physician Assistants (ASEPA) Adjunct Clinical Professor, PA Program James Madison University Harrisburg, Virginia Clinical Instructor, PA Program George Washington University Washington, DC Diabetes and Thyroid Associates Fredericksburg, Virginia Talk Outline Treating obesity as a chronic disease current recommendations Recognition/screening Therapeutic goals Assessing disease severity to determine treatment options Patient engagement Addressing obesity treatment with the individual patient Discussing disease history and severity Establishing individual goals Comprehensive lifestyle management core intervention for obesity management Components (reduced caloric intake, increased activity, behavior) Current recommendations Resources, tools, and tips to help your patients TREATING OBESITY AS A CHRONIC DISEASE

2 Reputable Sources of Treatment Recommendations for Adult Obesity Determining the Need to Treat Obesity AHA/ACC/TOS (Obesity 2) 1 : focus on lifestyle intervention with guidance on referral for surgery AACE 2 : algorithm based on assessment of disease severity ASBP 3 : comprehensive and holistic approach Endocrine Society 4 : detailed description of pharmacological intervention Screen 1-3 BMI is appropriate to identify individuals at elevated risk of obesityrelated complications Assess 1-3 Risk Presence and severity of complications to guide decisions regarding treatment modality and intensity AACE, American Association of Clinical Endocrinologists; ACC, American College of Cardiology; AHA, American Heart Association; ASBP, American Society of Bariatric Physicians; TOS, The Obesity Society. 1. Jensen MD, et al. Obesity. 214;22(suppl 2):S1-S Garber AJ, et al. Endocr Pract. 213;19 (suppl 2): Seger JC, et al. Obesity algorithm, presented by the ASBP. 4. Apovian CM, et al. J Clin Endocrinol Metab. 215 Jan 15. [Epub ahead of print]. 1. Jensen MD, et al. Obesity. 214;22(suppl 2):S1-S Garber AJ, et al. Endocr Pract. 213;19: Seger JC, et al. Obesity Algorithm, presented by the ASBP. Hazard Ratio BMI and Health Risk: Rationale for Weight Categories According to BMI 3.5 BMI and All-Cause Mortality 1,a Women Men BMI Range, kg/m 2 Category 2 BMI Range, kg/m 2 US Adults, % 3 Elevated Risk 2 Normal Overweight CVD Obese, class I CVD, all-cause mortality Obese, class II CVD, all-cause mortality Obese, class III 4 6 CVD, all-cause mortality a 19 studies including 1.46 million white adults (median age, Berrington de Gonzalez A, et al. N Engl J Med. 21;363:2211- years; 58% women) who never smoked and had no history of 2219; 2. Jensen MD, et al. Obesity. 214;22(suppl 2):S1-S41; cancer or heart disease at baseline; median follow-up of 1 years. 3. Ogden C, et al. JAMA. 214;311: Health Consequences of Overweight and Obesity Impact on Multiple Systems Depression/ psychological disorders, social stigmatization Gallbladder disease/nafld, GERD, pancreatitis Cancer (eg, breast, uterus, colon, esophagus, pancreas, kidney, prostate) Osteoarthritis, disability/immobility CHD, coronary heart disease; CVD, cardiovascular disease; GERD, gastroesophageal reflux disease; HTN, hypertension; NAFLD, nonalcoholic fatty liver disease; PCOS, polycystic ovary syndrome; T2DM, type 2 diabetes mellitus. Stroke Sleep apnea/respiratory CHD/CVD, HTN, dyslipidemia T2DM and prediabetes PCOS, reproductive disorders Urinary stress incontinence CDC. Overweight and obesity. Causes and consequences. Garvey WT, et al. Endocr Pract. 214;2: ; Seger JC, et al. Obesity algorithm, presented by the ASBP. Chen SM, et al. J Dig Dis. 212;13: General Goals of Obesity Management Assessing Disease Severity to Determine Treatment Options: Multiple Considerations Objective 1-3 Medical rather than cosmetic benefit Meaningful health improvements Greater losses = greater benefits 1-3 3%-5% meaningful improvement in some CV risk factors 1% substantial benefits in managing comorbidities (cardiometabolic, mechanical) Recommendations 1-3 5%-1% as initial goal (within 6 months) Once initial goal is met, reassess health goals and adjust therapy as necessary Anthropometric assessment 1-3 Example: BMI Only part of evaluation Limitations (eg, individual variability) Health status 1-3 Presence of complications Severity of complications Consider both to determine 1-3 Treatment need Treatment type Treatment intensity Approaches for staging obesity severity have been published 4,5 1. Jensen MD, et al. Obesity. 214;22(suppl 2):S1-S Garber AJ, et al. Endocr Pract. 213;19 (suppl 2): Seger JC, et al. Obesity algorithm, presented by the ASBP. 1. Jensen MD, et al. Obesity. 214;22(suppl 2):S1-S41; 2. Garber AJ, et al. Endocr Pract. 213;19 (suppl 2):1-48; 3. Seger JC, et al. Obesity algorithm, presented by the ASBP Sharma AM, Kushner RF. Int J Obes (Lond). 29;33: ; 5. Garvey WT, et al. Endocr Pract. 214;2:

3 You Can Make a Difference Please Discuss Weight Management With Your Patients PATIENT ENGAGEMENT If patients hear from a physician or other healthcare professional that they are overweight, they are 6 more likely to perceive themselves as overweight 2.5 more likely to attempt weight loss In this study 45.2% of individuals with BMI 25 had been told they were overweight 66.4% of individuals with BMI 3 had been told they were overweight Post RE, et al. Arch Intern Med. 211;171: Modified 5 A s: One Approach to Obesity Counseling in Primary Care 1,3 ASK for permission to discuss body weight create a dialogue that is: Nonjudgmental Safe Open ASSESS health status, obesity indicators, root causes of weight gain ADVISE patient of benefits and risks of weight loss, long-term strategy AGREE on goals and treatment expectations ARRANGE/ASSIST (or REFER) to identify barriers, resources, and providers identify, educate, recommend, support The clinician and patient should agree whether weight loss is appropriate in the context of competing priorities 2 1. Vallis M, et al. Can Fam Physician. 213;59: Jensen MD, et al. Obesity. 214;22(suppl 2):S1-S Seger JC, et al. Obesity algorithm, presented by the ASBP. Best Good OK Not good Bad Discussing Weight With Patients: Patients Preferred Terms Weight Weight problem, BMI, excess weight, unhealthy body weight Unhealthy BMI Excess fat, large size, obesity, heaviness Fatness Volger S, et al. Obesity. 212;2: Assess Weight and Lifestyle Histories to Identify Factors Contributing to Weight Gain and Barriers to Weight Loss Questions to ask History of weight gain and loss over time? Previous weight loss attempts? Dietary habits? Physical activity? Family history of obesity? Other medical conditions or medications that may affect weight? Answers may guide approach to adjusting weight-loss regimen Address/readdress contributing factors and barriers Intensify lifestyle/behavioral intervention Add adjunct therapies Optimize current regimens Jensen MD, et al. Obesity. 214;22(suppl 2):S1-S41. Optimize Current Regimens Medications for Coexisting Conditions May Promote Weight Gain Category Drugs That Cause Weight Gain Possible Alternatives Neuroleptics Tricyclics (ADs) Thioridazine, haloperidol, olanzapine, quetiapine, risperidone, clozapine Amitriptyline, nortriptyline, imipramine, doxepin Phenelzine Ziprasidone, aripiprazole Protriptyline, bupropion, nefazodone MAOIs (ADs) SSRIs (ADs) Paroxetine Fluoxetine, sertraline Other (ADs) Mirtazapine, duloxetine Bupropion Anticonvulsants Valproate, carbamazepine, gabapentin, Topiramate, lamotrigine, pregabalin, vigabatrin zonisamide, felbamate Antidiabetic agents Insulin, sulfonylureas, thiazolidinediones AGIs, DPP-4i s, SGLT2i s, GLP-1 RAs, metformin Antihistamines Cyproheptadine Inhalers, decongestants β- and α-adrenergic blockers Propranolol, doxazosin ACEIs, CCBs Steroid hormones Contraceptives, glucocorticoids, progestational steroids Barrier methods, NSAIDs Kushner RF, Ryan DH. JAMA. 214;312: ; Apovian CM, et al. J Clin Endocrinol Metab. 215 Jan 15. [Epub ahead of print].

4 Addressing Patient Expectations and Negotiating Reasonable Goals Are Important First Steps Patients Expectations for Obesity Treatment Outcomes 1,a If I achieved this weight loss 38% 33% 31% 25% 17% I would feel... that I achieved my dream weight..that I met my current goal happy that it was acceptable disappointed Patients may have ambitious goals and feel disappointed with modest loss 1 Patients and providers should agree on goals 2-4 COMPREHENSIVE LIFESTYLE MANAGEMENT CORE INTERVENTION FOR OBESITY MANAGEMENT a N = 6 women; mean starting weight = lb. 1. Foster GD, et al. J Consult Clin Psychol. 1997;65:79-85; 2. Jensen MD, et al. Obesity. 214;22(suppl 2):S1-S41; 3. Garber AJ, et al. Endocr Pract. 213;19 (suppl 2):1-48; 4. Seger JC, et al. Obesity algorithm, presented by the ASBP. Prescribe a Nutritional Plan to Reduce Caloric Intake Methods to Reduce Caloric Intake 1,2 Limit calories 1 Women: kcal/d Men: kcal/d Energy deficit (5 or 75 kcal/d) 1 Evidence-based diet that restricts certain food types (eg, high carbohydrate, high fat) 1,2 Very low calorie diet (< 8 kcal/d) ONLY 1 In limited circumstances With medical monitoring and high-intensity lifestyle intervention Consider Patient Preferences and Health Status 1 Preferably refer to a nutrition professional for counseling A variety of diets will promote weight loss 1. Jensen MD, et al. Obesity. 214;22(suppl 2):S1-S Seger JC, et al. Obesity algorithm, presented by the ASBP. U.S. News & World Report Best Weight-Loss Diets: Patients Have Many Options Diet Weight Watchers Description Point system based on food characteristics encourages healthy choices; group support available Meal replacements, fruits, vegetables; quick start and transition HMR Diet phases; lifestyle training; weekly coaching; home or clinic Biggest Loser Diet Books providing guidance on calorie restriction and exercise Jenny Craig Personalized prepackaged meal/exercise plan with support a 75% to 8% of daily foods are plant based and not heated above Raw Food Diet 115 F; substantial preparation time Volumetrics Focus on low-density, high-volume foods Atkins Low carb; frozen food line is available Flexitarian Diet Mostly vegetarian; outlined 5-week meal plan Slim-Fast Meal replacement program Vegan Diet Excludes all animal products HMR, Health Management Resources. U.S. News and World Report. Best diets 215. a Consultants with access to expertise of registered dietitians. Consider Commercial Programs That Have Features Consistent With Recommendations 1-3 Self-monitoring weight and diaries Portion control meal replacements Regular, moderate physical activity Social support individual and group sessions Incremental steps to behavior change Option for long-term participation or weight maintenance support Examples: Weight Watchers, Jenny Craig, TOPS, NutriSystem, YMCA Diabetes Prevention Program Prescribe Increased Physical Activity Prescription 1,2 Include frequency, intensity, time spent, type, enjoyment level, and default and back-up plans 2 15 min/week moderate or 75 min/week vigorous aerobic activity 1,2 Resistance training to preserve lean mass 2 > 2-3 min/week moderate or > 15 min/week vigorous aerobic activity for more robust weight loss and to prevent weight regain 1,2 Accounting records eg, written or electric activity logs, pedometer/accelerometer logs, metrics (miles, laps, reps) 2 1. Moyer V, et al. Ann Intern Med. 212;157: Jensen MD, et al. Obesity. 214;22(suppl 2):S1-S Wadden T, et al. Circulation. 212;125: Jensen MD, et al. Obesity. 214;22(suppl 2):S1-S Seger JC, et al. Obesity algorithm, presented by the ASBP.

5 Encourage Patients to Also Increase Non-training Activity Priority is to increase energy expenditure and decrease sedentary time Leisure time Competitive sports Noncompetitive sports (eg, hiking, cycling) Nonsport alternatives (dancing) Daily activities Walk instead of using motorized transportation Use stairs instead of elevators or escalators Carry overnight travel bags instead of using rollers Avoid prolonged inactivity What Does the State-of-the-Art Effective Lifestyle Intervention Look Like? Look AHEAD Study Academic setting Trained TEAM of interventionists Personal weight loss goal 1% a Weight-loss induction (months 1-6) 1 individual and 3 group sessions/month Lots of contact! Weight-loss maintenance (months 7-12) 1 individual and 2 group sessions/month Participants expected to attend at least 1 group session Weight-loss maintenance (years 2-4) Monthly individual counseling (face-to-face, phone call, or ) Refresher courses 2 to 3 times/year (6-8 weeks each) Seger JC, et al. Obesity algorithm, presented by the ASBP. a Study weight loss goal 7%. Look AHEAD Research Group. Obesity. 26;14: Look AHEAD clinical trial protocol. Prescribe a Program That Offers Behavioral Intervention Ideal Initiation High contact frequency 1,2 14 group or individual sessions in 6 months 1 On-site, highintensity program with behavioral strategies 1,2,b a Includes goal setting, self-monitoring; b Health professionals (eg, registered dietitians, psychologists, exercise specialists, health counselors), and lay persons who were trained in and used formal weight-management protocols. Alternatives 1,2 Telephone or electronic counseling (with personalized feedback) Commercial programs with evidence of safety and efficacy Maintenance 1,2 Continued contact ( 1 /month) a Counseling/sessions/contact should be with trained interventionist(s) 1,b Face-to-face is recommended 1 May pose barriers (time, expense, loss of anonymity) 3 Electronic delivery may result in less weight loss than face-to-face 1 1. Jensen MD, et al. Obesity. 214;22(suppl 2):S1-S41; 2. Seger JC, et al. Obesity algorithm, presented by the ASBP Sullivan DK, et al. J Nutr Educ Behav. 213;45: Additional Resources and Tools to Facilitate Self-Monitoring and Planning Pedometers and sports watches 1 Personal-activity monitors (eg, BodyMedia FIT, DirectLife, Fitbit One, Fitbit Zip, ActiGraph, Jawbone Up, Basis B1) 2 Phone applications (eg, Calorie King, 3 GoMeals, 3 Fitter Fitness Calculator, 3 SparkPeople, 3 Strava Cycling, 3 South Beach Diet, 3 Charity Miles, 4 LiveStrong, 5 MyFitnessPal 6 ) Internet (eg, ChooseMyPlate, SparkPeople, 1. Meyer J, Hein A. Medicine ;2.e7. 2. Lee JM, et al. Med Sci Sports Exerc. 214;46(9): Diabetes Forecast Neithercott C. Diabetes apps LiveSTrong mobile apps. MyPlate calorie tracker MyFitnessPal. Apps. Summary Obesity management recommendations include Screening criteria to identify individuals who may benefit from treatment (eg, BMI 25) Assessment of disease severity to inform individualized management Patient-focused, unbiased communication approaches (eg, 5 A s, appropriate word choice) promote Productive patient and clinician collaboration Efforts to identify and address contributing factors and management barriers Identification of appropriate treatment options Comprehensive lifestyle management is the cornerstone for the management of overweight and obesity Behavioral intervention Reduced calorie intake Increased physical activity Clinicians and patients can leverage many evidence-supported resources, approaches, and tools for individualized lifestyle management CASE PRESENTATION

6 Patient Description: Tamara Female 38 years old Married, 2 children (12 and 8) High school teacher Follow-up for prediabetes and weight 1 year after starting DPPbased comprehensive lifestyle program Lost 8% (19 lb/9 kg) in 6-month intensive phase Regained 13 lb (7 kg) since transitioning to 1-year maintenance phase 6 months ago Current medications Paroxetine 3 mg/d initiated by psychiatrist 3 months ago Atorvastatin 1 mg/d for past 2 years DPP, Diabetes Prevention Program Indicator Height, in (cm) Weight, lb (kg) 1 Year Ago 71 (18) 242 (11) 6 Mo Ago 71 (18) 223 (11) Today 71 (18) 236 (18) BMI, kg/m BP, mm Hg 144/88 136/78 14/85 FBG, mg/dl A1C, % Cholesterol, mg/dl Total LDL-C HDL-C 46 5 TG QUESTION-AND-ANSWER SESSION Talk Outline Adjunct Therapeutic Approaches for Management of Adult Obesity Donna H Ryan, MD Professor Emerita Pennington Biomedical Research Center Baton Rouge, Louisiana Adjunct therapies for long-term weight management When are they appropriate? What is their role in weight management? Who are good candidates? Pharmacotherapy for long-term weight management Talking to your patient about pharmacotherapy Therapeutic expectations Efficacy Safety and tolerability Agent-specific considerations Impact on complications Bariatric surgery for long-term weight management Talking to your patient about bariatric surgery Therapeutic expectations Efficacy Safety and tolerability Impact on complications General Recommendations Regarding Therapeutic Options for Adult Obesity 1-3 Comprehensive lifestyle management - First intervention appropriate for all levels of disease severity - Patient candidates - BMI 3 - BMI 25 to 29.9 with risk factors a - Other approaches are adjunct to this core approach Adjunct Therapies Principles to Guide Choice of Therapies Use lower-risk approaches for individuals at lower risk Reserve higher-risk approaches for those at highest risk Harms are small 1 Lifestyle 5 Contraindications, precautions, warnings, AEs 2 Medication + lifestyle 6 Gastric band 7,8 Reserved for severe disease Extensive care Invasive possible complications 3,4 Gastric bypass 7,8 Pharmacotherapy - Patient candidates - BMI BMI 27 with obesity complication/manifestation a AACE lifestyle modification is also appropriate for individuals with BMI of 25 to 29.9 with no complications, with less emphasis on weight loss, more on preventing weight gain. b AACE severe comorbidity; ASBP BMI 3 with complication. Bariatric surgery - Reserved for more severe disease - Patient candidates - BMI BMI 35 with obesity complication/manifestation b 1. Jensen MD, et al. Obesity. 214;22(suppl 2):S1-S Garber A, et al. Endocr Pract. 213;19(suppl 2): Seger JC, et al. Obesity algorithm, presented by the ASBP. % 5% 1% 15% 2% 25% 3% 35% Approximate Mean Weight Loss 1. Moyer V, et al. Ann Intern Med. 212;157: ; 2. US FDA. Drugs@FDA Fried M, et al. Obes Facts. 213;6: ; 4. Mechanick JI, et al. Obesity. 213;21(suppl 1):S1-S27; 5. Jensen MD, et al. Obesity. 214;22(suppl 2):S1-S41; 6. Colman E, et al. N Engl J Med. 212;367: ;7. LABS Consortium. N Engl J Med. 29;361: ; 8. Courcoulas AP, et al. JAMA. 213;31:

7 Expert Pearls Regarding Adjunct Therapies for Obesity Management Lifestyle management is the core therapy for obesity management everything else is added to this 1-4 Adjunct therapies are an option for those who struggle to lose weight and/or maintain weight loss 1-4 Lifestyle management may need to be adjusted when adjunct therapy is added for example Low-fat diet should be used with orlistat 5 Smaller food portions are required with bariatric surgery 6 Medications employed for weight management should be approved for the indication 1-4 Use according to product label 1-4 Use lowest recommended dose that provides effective weight loss 4 PHARMACOTHERAPY 1. Jensen MD, et al. Obesity. 214;22(suppl 2):S1-S41; 2. Garber AJ, et al. Endocr Pract. 213;19 (suppl 2):1-48; 3. Seger JC, et al. Obesity algorithm, presented by the ASBP Apovian CM, et al. J Clin Endocrinol Metab. 215 Jan 15. [Epub ahead of print]; 5. US FDA. Drugs@FDA Mechanick JI, et al. Obesity. 213;21(suppl 1):S1-S27. Discussing Long-Term Weight Management With Patients: Pharmacological Agents Practice shared decision making with patient engage in discussion of potential risks/benefits and whether a medication is right for them Because obesity is a chronic disease, long-term management is required Pharmacological agents are used as an adjunct to lifestyle modification 1 Agents approved for short-term use 1,2 Modest weight loss ( 3-4 kg over 1 year) Should be discontinued after 12 weeks not approved for long-term use Agents approved for long-term use 1,2 Modest but clinically significant weight loss (5%-1%) Important to take as prescribed and monitor for efficacy and adverse effects Increase to maximum dose or discontinue if an agent is not effective a May consider an alternative agent if one is not effective Cost may not be covered by insurance FDA-Approved Medications for Obesity Management: Short-Term Use a Agent Mechanism Mean Short-Term Weight Change vs PBO 2 Phentermine b,c Schedule IV 3.6 kg (2-24 weeks) Diethylpropion b Schedule IV Phendimetrazine b,c Schedule III Benzphetamine b Schedule III Noradrenergic causing appetite suppression 3. kg (6-52 weeks) No trials met inclusion criteria 3.3 kg ( weeks) Common adverse events 1 : insomnia, elevated heart rate, dry mouth, altered taste, dizziness, tremors, headache, diarrhea, constipation, vomiting, gastrointestinal distress, anxiety, restlessness a For all but orlistat, discontinue if 5% weight loss (4% with liraglutide 3. mg) is not achieved after 12 weeks on maximum/maintenance dose US FDA. Drugs@FDA. 2. Yanovski SZ, Yanovski JA. JAMA. 214;311: a Usually considered 12 weeks. b Approved for adults with BMI 3 kg/m 2. c Approved for adults with BMI 27 kg/m 2 in the presence of other risk factors. 1. Yanovski SZ, Yanovski JA. JAMA. 214;311: Haddock et al, Int J Obes Relat Metab Disord. 22;26: US FDA. Drugs@FDA. Contraindications and Warnings/Precautions for Obesity Medications for Short-Term Use Contraindications 1 CVD history/advanced arteriosclerosis a Recent MAOI use b Hyperthyroidism Glaucoma Agitated states History of drug abuse Pregnancy c B, benzphetamine; CI, contraindication; D, diethylpropion; P, phentermine; Pz, phendimetrazine. a Approved before requirement for long-term outcome studies; risk of CV events cannot be excluded. b Within 2 weeks. c Category X, except Category B for diethylproprion. Warnings/Precautions 1 Use with other anorectic agents (CI for D, Pz) Pulmonary hypertension (CI for D) Valvular heart disease Tolerance (discontinue) Alcohol use Hypertension (CI for B, if moderate to severe) Use with antihyperglycemic agents Possible impairment (caution patients) Nursing (CI for P, Pz) Convulsions with epilepsy (D) 1. US FDA. Drugs@FDA. Mechanisms of Action of Medications Approved in the United States for Long-Term Weight Management Agent Orlistat 1,2 Lorcaserin 1,2 Schedule IV Phentermine/topiramate ER 1,2 Schedule IV Naltrexone ER/bupropion ER 2 Liraglutide 3. mg 2 Mechanism of Action Lipase inhibitor Fat excretion in stool Serotonin receptor agonist Appetite suppression Sympathomimetic/antiepileptic Appetite suppression Opioid antagonist/antidepressant Appetite regulation, reward system GLP-1 RA Appetite suppression 1. Yanovski SZ, Yanovski JA. JAMA. 214;311: US FDA. Drugs@FDA.

8 Therapeutic Efficacy of Medications Approved in the United States for Long-Term Weight Management Agent Dosage (oral, except sc for liraglutide 3. mg) 1 1-Year Efficacy, Difference vs PBO 1 Weight, % Pts Losing Pts Losing 5% of Initial 1% of Initial Weight, % Weight, % Orlistat 12 mg, 3 daily a b 12 b Lorcaserin 1 mg, 2 daily Phentermine/ topiramate ER c Naltrexone ER/ bupropion ER d 7.5 mg/46 mg 1 daily 16 mg/18 mg 2 daily Liraglutide 3. mg, 1 daily All differences significant vs PBO (P <.5) Patients in Category, % Medications for Long-Term Use: Categorical Results (5%) in Trials Longer Than 1 Year PBO 37 ORL 53 5% Loss (4 years) 1,b Patients in Category, % a PBO P/T (7.5/46) % Loss (18 weeks) 2,b 1 P <.1 for all comparisons of active agents vs comparator Patients in Category, % ORL LIRA 2.4/ > 5% Loss (2 years) 3,c a Prescription dose; 6 mg over-the-counter version has been recalled 2 ; b Estimate calculated as difference between averages across 5 trials for each treatment group; c 15 mg/92 mg dose, only for use if 7.5 mg/46 mg is not effective, yielded 9% weight loss vs PBO; d Efficacy data from COR-I trial. 1. US FDA. Drugs@FDA. 2. US FDA. Safety alerts for human medical products. yalertsforhumanmedicalproducts/ucm39113.htm. LIRA, liraglutide; ORL, orlistat; P/T, phentermine/topiramate; PBO, placebo. a With P/T(15/92), which is only for use if 7.5 mg/46 mg is not effective, 79% had 5% weight loss 4 ; b Completer population; c Intent-to-treat population, last observation carried forward. 1. Torgerson JS, et al. Diabetes Care. 24;27: Garvey WT, et al. Am J Clin Nutr. 212;95: Astrup A, et al. Int J Obes (Lond). 211;36: US FDA. Drugs@FDA. Medications for Long-Term Use: Categorical Results (1%) In Trials Longer Than 1 Year Patients in Category, % 1 PBO 16 ORL 26 1% Loss (4 years) 1,b Patients in Category, % LIRA, liraglutide; ORL, orlistat; P/T, phentermine/topiramate; PBO, placebo. a With P/T(15/92), which is only for use if 7.5 mg/46 mg is not effective, 54% had 1% weight loss 4 ; b Completer population; c Intent-to-treat population, last observation carried forward. a PBO P/T (7.5/46) % Loss (18 weeks) 2,b Patients in Category, % 1 P <.5 for all comparisons of active agents vs comparator ORL LIRA 2.4/ > 1% Loss (2 years) 3,c 1. Torgerson JS, et al. Diabetes Care. 24;27: Garvey WT, et al. Am J Clin Nutr. 212;95: Astrup A, et al. Int J Obes (Lond). 211;36: US FDA. Drugs@FDA. BW Change, % Orlistat 1,a Placebo Orlistat (12 mg) -4-8 Weight Regain After Crossover to Placebo Week SB DB DB Slightly hypocaloric diet Weight maintenance (eucaloric) diet Mean BW, kg 1 BW, body weight; DB, double-blind; PBO, placebo; SB, single-blind lead-in. a ITT population (N = 683 for year 1; N = 519 for year 2; 83% female); mean baseline characteristics: BMI, 36 kg/m 2 ; age, years; b Participants continuing past year 1, rerandomized at year 2 (N = 1523; 83%-84% female at year 1 baseline); mean baseline characteristics (start of year 1): BMI, 36 kg/m 2 ; age, 44 years. 96 Lorcaserin 2,b Year 1 Year Week PBO in years 1 and 2 Lorcaserin (1 mg) in year 1, PBO in year 2 Lorcaserin in years 1 and 2 1. Sjöström L, et al. Lancet. 1998;352: Smith SR, et al. N Engl J Med. 21;363: Weight-Loss Maintenance and Loss With Medication After Low-Energy Diet a LIRA 3. mg: PBO: Change in Body Weight, % n = 27 n = 26 n = 156 n = 144 S Run-in Treatment period F n = 153 n = ± 21. kg 2.2% -2 PBO % c -6 LIRA 3. mg Time, weeks LIRA 3. mg vs PBO Maintained run-in loss ( 5%): 81% vs 49% c Lost 5% during treatment period: 51% vs 22% c Lost 1% during treatment period: 26% vs 6% c S, screening; F, follow-up. a LIRA 3. mg vs PBO after 4 to 12 weeks of low-energy diet (12-14 kcal/d); N = 422; mean run-in weight (week 12) = 15.9 kg; mean randomization weight (week ) = 99.6 kg; c P <.1 vs PBO. Wadden T, et al. Int J Obes (Lond). 213;37: Agent Orlistat Medications for Long-Term Weight Management: Common Adverse Effects Lorcaserin Phentermine/ topiramate ER Naltrexone ER/ bupropion ER Liraglutide 3. mg a More common than with PBO and in > 5% of patients. Common Adverse Effects a Oily spotting, flatus with discharge, fecal urgency, fatty oily stool, increased defecation, fecal incontinence Headache, fatigue, dizziness, nausea, dry mouth, constipation Paresthesia, dizziness, distorted taste, insomnia, constipation, dry mouth Nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, diarrhea Nausea, hypoglycemia (in T2DM), diarrhea, constipation, vomiting, headache, decreased appetite, dyspepsia, fatigue, dizziness, abdominal pain, increased lipase levels US FDA. Drugs@FDA.

9 Medications for Long-Term Weight Management: Contraindications a Medications for Long-Term Weight Management: Warnings and Precautions Orlistat Pregnancy Chronic malabsorption syndrome Cholestasis Lorcaserin Pregnancy Phentermine/topiramate ER Pregnancy Glaucoma Hyperthyroidism During or within 14 days of taking MAOIs MAOIs, monoamine oxidase inhibitors; MEN 2, multiple endocrine neoplasia syndrome type 2; MTC, medullary thyroid carcinoma. a Known hypersensitivity to agent or any component of this product included for all agents. Naltrexone ER/bupropion ER Pregnancy Uncontrolled hypertension Seizure disorders; anorexia nervosa or bulimia; abrupt discontinuation of alcohol, benzodiazepines, barbiturates, antiepileptic drugs Use of other bupropioncontaining products Chronic opioid use During or within 14 days of taking MAOIs Liraglutide 3. mg Pregnancy Personal or family history of MTC or MEN 2 US FDA. Drugs@FDA. Orlistat Cyclosporine exposure Supplement (fat-soluble vitamins) Liver injury (rare) Urinary oxalate monitor if risk of RI Substantial weight loss can increase the risk of cholelithiasis GI effects with high-fat diet Lorcaserin Serotonin syndrome or NMS-like reactions Valvular heart disease Cognitive impairment Psychiatric disorders Depression/suicidal thoughts Hypoglycemia a Priapism NMS, neuroleptic malignant syndrome; RI, renal insufficiency. a When used with antidiabetic medications. Phentermine/topiramate ER Fetal toxicity Heart rate Suicidal behavior/ideation Acute myopia and secondary angle-closure glaucoma Mood and sleep disorders Cognitive impairment Metabolic acidosis Elevated creatinine levels Hypoglycemia a US FDA. Drugs@FDA. Medications for Long-Term Weight Management: Warnings and Precautions (cont) Naltrexone ER/bupropion ER Suicidal thoughts and behaviors Neuropsychiatric reactions Seizure risk adhere to dosing schedule and avoid administration with a high-fat meal to limit risk Increased BP and HR monitor Hepatotoxicity (naltrexone) Angle-closure glaucoma (antidepressant) Hypoglycemia a Liraglutide 3. mg Risk of thyroid C-cell tumors Acute pancreatitis Acute gallbladder disease Increased HR monitor Renal impairment Hypersensitivity Suicidal behavior and ideation Hypoglycemia a Boxes indicate boxed warnings in prescribing information Impact of Medications Approved for Long-Term Use on Obesity-Associated Complications (T2DM) Agent A1C, % A1C < 7%, % of patients A1C 6.5%, % of patients Agent PBO Agent PBO Agent PBO Orlistat 1.9 a, b.6 Other CV Risk Factors With Significant Improvement vs PBO LDL-C, TC, LDL/HDL, SBP Lorcaserin 2.9 a a,c 26.3 c 23.9 a 8.6 HDL-C, WC Phentermine/ topiramate ER 3,d 1.6 a a,c 4 c 32 a 16 SBP Naltrexone ER/ bupropion ER 4,e.6 a a a 1.2 HDL-C, TG, WC Liraglutide 3. mg 5,6 1.3 a a a 12. WC a When used with antidiabetic medications. US FDA. Drugs@FDA. SBP, systolic blood pressure; TC, total cholesterol; TG, triglycerides; WC, waist circumference. a P <.5 vs PBO; b Adjusted for changes in diabetes medications; c 7%; d Maximum dose (15 mg/92 mg). 1. Miles JM, et al. Diabetes Care. 22;25: ; 2. O Neil PM, et al. Obesity. 212;2: ; 3. Garvey WT, et al. Diabetes Care. 214;37: ; 4. Hollander P, et al. Diabetes Care. 213;36: ; 5. Davies M, et al. ADA 74th Scientific Sessions. 214 [abstract 97-OR]; 6. Astrup A, et al. Lancet. 29;374: Discussing Long-Term Weight Management With Patients: Bariatric Surgery For appropriate candidates, bariatric surgery may be a good option for improving health 1 BARIATRIC SURGERY Offer appropriate candidates referral to an experienced bariatric surgeon 1 BMI 4 or 35 with complications/manifestations of obesity who are motivated to lose weight Insufficient response to comprehensive lifestyle management with or without medication Ensure that patients are fully informed regarding risks, benefits, options (procedure, surgeon, institution), and long-term follow-up 2 1. Jensen MD, et al. Obesity. 214;22(suppl 2):S1-S Mechanick JI, et al. Obesity. 213;21(suppl 1):S1-S27.

10 Longitudinal Assessment of Bariatric Surgery-2 (LABS-2): Major Clinical Outcomes at 3 Years 1,a LABS-2: Mortality and Subsequent Bariatric Surgery at 3 Years 1 Weight Change, % LAGB Median, observed Modeled RYGB Median, observed Modeled Follow-Up Time, y LAGB, laparoscopic adjustable gastric band; RYGB, Roux-en-Y gastric bypass; SG, sleeve gastrectomy. a Prospective, observational study initiated in 26 at multiple US centers to assess longer-term outcomes. Observed Remission Rates, % Comorbidity RYGB LAGB Diabetes Dyslipidemia Hypertension Weight loss with SG procedure, based on recent meta-analysis 2 Greater than LAGB Similar to RYGB 1. Courcoulas AP, et al. JAMA. 213;31: Chang S, et al. JAMA Surg. 214;149: RYGB (n = 1738) LAGB (n = 61) Event Events/ Events/ N 3 P-Y a N 3 P-Y a Mortality, within 3 days 3 b.2 Mortality, after 3 days Subsequent bariatric surgery 4 c.3 77 d 17.5 Longer-term and detailed complication data are being collected 1 Patient characteristics (eg, history of DVT/VTE) have been associated with 3-day major adverse outcomes, including mortality 2 Recent meta-analysis suggests that mortality and complication rates with SG are between those with LAGB and RYGB 3 DVT, deep vein thrombosis; VTE, venothromboembolism. a Events per 3 person-years: estimated number of events if 1 patients were followed for 3 years. b Sepsis (1), CVD (1), pulmonary embolism (1). c Revision (2), reversal (2). d Band replacement (7), port revision (19), other revision (1), band removal (21), revision to another bariatric procedure (2). 1. Courcoulas AP, et al. JAMA. 213;31: Flum DR, et al. N Engl J Med. 29;361: Chang S, et al. JAMA Surg. 214;149: Summary Adjunct therapies (pharmacotherapy, bariatric surgery) are generally reserved for individuals with greater health risk due to complications/manifestations of obesity 5 medications are currently approved for long-term obesity management in the United States Different mechanisms of action and clinical profiles, particularly related to contraindications, safety, and tolerability More options in case of contraindications, tolerability issues, lack of efficacy CASE PRESENTATION Bariatric surgery may be an appropriate option for some individuals with obesity Patient Update: Tamara Follow-up for weight management and prediabetes 12 weeks since last appointment Based on plan developed at previous visit Switched antidepressants Began attending Weight Watchers Lost 6 lbs in first 4 weeks; weight has been stable since Current medications Bupropion 15 mg twice daily for past 3 months Atorvastatin 1 mg/d for past 2 years Indicator 12 Weeks Ago This Visit Height, in (cm) 71 (18) 71 (18) Weight, lb (kg) 236 (18) 23 (18) BMI, kg/m BP, mm Hg 14/85 142/83 FBG, mg/dl A1C, % Cholesterol, mg/dl Total LDL-C HDL-C 5 49 TG