1. 3 Steps to Successful Obesity Management

2. Learning objectives Review recent findings about the biologic regulation of eating and weight control Discuss the clinical recommendations and benefits of sustained weight loss in overweight and obese patients Apply principles of motivational interviewing and shared decision-making to improve the clinical management of obesity and promote behavioral changes Understand current guidelines for managing obesity, including the role of pharmacological therapy as an adjunct to lifestyle changes in reducing weight gain and promoting weight loss Review reimbursement options for intensive behavioral therapy (IBT) in obesity management

3. Disclosures Brought to you by a medical education collaboration between the Louisiana Osteopathic Medical Association and the Endocrine Society. Developed by Knighten Health. Supported by an education grant from Novo Nordisk Inc. Janet Ricks, DO: No relevant financial relationships with any commercial interests

4. The case for putting weight first

5. How much body weight does a patient with obesity need to lose to lower his or her risk of health problems and death? A.10% B.25% C.3% D.8%

6. Obesity is a complex and multifactorial disease 1-6 1. Woods SC et al. Int J Obes Relat Metab Disord. 2002;26(suppl 4):S8-S10. 2. Ludwig DS. JAMA. 2014;311:2167-2168. 3. Speliotes EK et al. Nat Genet. 210;42:937-948. 4. Garvey WT et al. Endocr Pract. 2014;20:977-989. 5. Bray GA, Ryan DH. Ann NY Acad Sci. 2014;1311:1-13. 6. The Obesity Society Infographic Task Force, November 2015. http://www.obesity.org/obesity/resources/facts-about-obesity/infographics. Accessed December 10, 2015. Energy balance ExpenditureIntake Gut microbiota Fat cells Genetics/ epigenetics Medications Environment

7. Obesity is “getting worse in this country,” rapidly Ogden CL, Carroll MD, Flegal KM. JAMA. 2014 Jul;312(2);189-90. BMI <18.518.5-24.925.0-29.930.0-34.935.0-39.9>40 underweightnormaloverweightobesity Iobesity IIobesity III U.S. adult population 31%34%20.6%8.1%6.4% 35.1% obese 69% overweight and obese More than two-thirds of U.S. adults

8. Overweight and Obesity Increase Risk of Disease Ogden CL, Carroll MD, Flegal KM. JAMA. 2014 Jul;312(2);189-90. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity Obes Res. 1998;6(suppl 2). BMI <18.518.5-24.925.0-29.930.0-34.935.0-39.9>40 underweightnormaloverweightobesity Iobesity IIobesity III Extremely High Disease risk relative to normal weight and waist circumference Very HighHigh Waist Circumference: Men > 40 in, Women > 35 in

9. As little as 3% - 5% weight loss reduces the risk of disease Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity Obes Res. 1998;6(suppl 2). BMI <18.518.5-24.925.0-29.930.0-34.935.0-39.9>40 underweightnormaloverweightobesity Iobesity IIobesity III Extremely High Disease risk relative to normal weight and waist circumference Very HighHigh Waist Circumference: Men > 40 in, Women > 35 in

10. Why is losing weight and keeping it off so difficult?

11. Morton GJ, Meek TH, Schwartz MW. Nat Rev Neurosci. 2014 Jun;15(6):367-78. Obesity as an endocrine-related disease American Medical Association (AMA) recognizes obesity as a disease: It is a multi-metabolic and hormonal disease state It has characteristic signs and symptoms Increase in fat mass associated with obesity is directly related to comorbidities such as type 2 diabetes mellitus, cardiovascular disease, and some types of cancer Disease results through a perturbation in the central nervous system (CNS) regulation of energy homeostasis Under normal conditions, food intake and energy expenditure are balanced by a homeostatic system that maintains stability of body fat content over time. Obesity results through a perturbation in CNS regulation of energy homeostasis.

12. Multiple hormonal signals influence hypothalamic neurons and appetite 1-3 1. Woods SC et al. Int J Obes Relat Metab Disord. 2002;26(suppl 4):S8-S10. 2. Suzuki K et al. Exp Diabetes Res. 2012;2012:824305. 3. Valassi E et al. Nutr Metab Cardiovasc. 2008;18:158-168. Gut GLP-1, CCK, PYY Fat cells Leptin Increases appetite Suppresses appetite Pancreas Insulin, Amylin Stomach Ghrelin Appetite

13. Physiology of reduced obese state Metabolic and hormonal changes drive weight regain The metabolic handicap: reduction in energy expenditure disproportionate to weight reduction. Mr. Smith 220 pounds needs 2200 kcal/day Loses weight to 200 pounds Needs 1830 kcal/day ↑ hunger, ↓satiety Mr. Jones 200 pounds needs 2000 kcal/day ≠ Smith Jones

14. 30 lb LOSS 11 lb GAIN Long-term persistence of hormonal adaptations to weight loss Sumithran P et al. N Engl J Med. 2011;365:1597-1604. Changes in Weight from Baseline to Week 62 10 week weight-loss program

15. 14% weight loss produced changes in 8 hormones that encourage weight regain Sumithran P et al. N Engl J Med. 2011;365:1597-1604. 14% weight loss reduced: 14% weight loss increased: Leptin – 65% Peptide YY Cholecystokinin Insulin Amylin Ghrelin Pancreatic polypeptide Gastric inhibitory polypeptide Measures of appetite Mean fasting and postprandial levels of some peripheral signals at baseline and 62 weeks 10-week, lifestyle-based weight loss intervention in healthy overweight and obese adults (n=34) led to sustained elevations in appetite stimulating hormone(s) and decreases in appetite suppressing hormones Net result of these hormonal changes is WEIGHT GAIN!

16. What are the risks of overweight? How much weight loss is needed for health benefit?

17. Pulmonary disease Abnormal function Obstructive sleep apnea Hypoventilation syndrome Nonalcoholic fatty liver disease Steatosis Steatohepatitis Cirrhosis Coronary heart disease Diabetes Dyslipidemia Hypertension Gynecologic abnormalities Abnormal menses Infertility Polycystic ovarian syndrome Osteoarthritis Skin Gall bladder disease Cancer Breast, uterus, cervix, colon, esophagus, pancreas, kidney, prostate Phlebitis Venous stasis Gout Obesity and comorbidities Idiopathic intracranial hypertension Stroke Cataracts Severe pancreatitis

18. Modest weight loss has benefits, with greater weight loss associated with greater benefit Measures of glycemia 1 -3% Triglycerides 1 HDL cholesterol 1 -5% Systolic and diastolic blood pressure Hepatic steatosis measured by MRS 2 Measures of feeling and function: Symptoms of urinary stress incontinence 3 Measures of sexual function 4,5 Quality of life measures(IWQOL) 6 NASH Activity Score measured on biopsy 7 -10% Apnea-hypopnea index 8 Reduction in CV events, mortality, remission of T2DM -15% 1. Wing et al. Diabetes Care 2011;34:1481-1486. 2. Lazo et al. Diabetes Care 2010;33:2156–2163. 3. Phelan et al. Urol. 2012;187:939-944. 4. Wing et al. Diab Care 2013;36:2937-2944. 5. Wing et al. Journal of Sexual Medicine 2010 ; 7:156-65. 6. Crosby, Manual for the IWQOL-LITE Measure. 7. Promrat et al. Hepatology 2010;51:121–129. 8. Foster et al. Arch Intern Med 2009;169:1619–1626

19. Why is modest weight loss beneficial? Adapted from: Després J, et al. BMJ. 2001;322:716-720. SCAT = Subcutaneous Adipose Tissue VAT = Visceral Adipose Tissue VAT Abdominal obesity, increased waist circumference After weight loss, reduced waist circumference DeteriorationLipid profileImprovement ImpairedInsulin sensitivityImproved  Blood insulin   Blood glucose   Risk markers for thrombosis   Inflammatory markers  Impaired Endothelial function Improved 10% weight loss = 30% VAT Loss Increased riskLowered risk

20. Summary (Risks of overweight & obesity, Benefits of weight modest weight loss) Obesity is associated with an increased risk for coronary heart disease, type 2 diabetes, various types of cancer, gallstones, and disability. Obesity is associated with an increased risk for death, particularly in adults younger than 65 years. The risk of disease increases with BMI and waist circumference. Weight loss as little as 3% - 5% in obese individuals is associated with a lower incidence of health problems and death.

21. Obesity is a disease, but are we talking about it? USPSTF recommends screening all adults for obesity yet: A third of patients with a BMI ≥ 30 were never told by their doctors that they have obesity Rates of physician counseling appear to be decreasing, by as much as 25 percent. Those rates are worse for patients with obesity co-morbidities Family practitioner–patient conversations about nutrition last an average of 55 seconds Intensive behavioral counseling can induce clinically meaningful weight loss, but there is little research on primary care practitioners providing such care Post RE et al. Arch Intern Med. 2011;171(4):316-321 Kraschnewski JL et al. Med Care. 2013;51:186–92. Eaton CB, Am J Prev Med. 2002 Oct;23(3):174-9. Wadden TA et al. JAMA. 2014 Nov 5;312(17):1779-91

22. How much body weight does a patient with obesity need to lose to lower his or her risk of health problems and death? A.10% B.25% C.3% D.8%

23. STEP 1: Talk to patients about obesity Motivational interviewing and shared decision-making with patients

24. What is the first thing you should do when discussing weight with patients? A.Recommend a diet. B.Ask permission to discuss weight. C.Ask about their exercise routines. D.Explain a high BMI's health risks.

25. Meet Rosalia: Working mom with a family history of type 2 diabetes CC: in for annual visit. SH: 49-year-old office manager for Blue Cross, recently promoted, divorced, 2 children Does not smoke or drink Took paroxetine around time of divorce for depression – continues on it. Her father has T2DM and is on dialysis; She says “I know this runs in families and I don’t want it to happen to me. Meds: Has been on paroxetine since her divorce 4 years ago, asymptomatic. Workup Height: 5’8”; weight: 223 lbs; BMI: 34 kg/m 2 (comments: “I need to lose at least 80 pounds”) BP: 130/80 mm; pulse: 70 bpm, Resp: WNL Mammogram report: normal Lab Chem Survey: glucose 107, A1c 5.8%, otherwise normal. Cholesterol 238, HDL 64, TG 124, LDL 149. CBC & UA normal. TSH 3.91. Pap smear normal.

26. How do you think about your patients’ weight struggles? What you might think: She needs to lose at least 80 pounds. I need to start her on metformin, advise her to lose weight and see her back in a year. She can lose weight by just eating a bit less and exercising a bit more. I will tell her about healthy lifestyle. If she struggles, she just needs more resolve. She doesn’t need medications. She can do this on her own. The reality: She can greatly reduce her risk for diabetes with loss of just 11 - 22 pounds. She can improve risk for diabetes, BP, and lipids with weight loss. This needs to be the first and central approach. Weight loss requires skills training. The more intensive the coaching, the greater the chance of meaningful weight loss. Some of her medications caused her to gain weight. She may need help with medications both to lose weight and to address biologic adaptations to weight loss.

27. The 5As of Obesity Management Vallis M, et al. Can Fam Physician. 2013;59:27-31; ​ Meriwether RA, et al. Am Fam Physician. 2008;77(8):1129-3. Ask Ask for permission to discuss weight Explore readiness for change Assess Assess obesity class and stage Assess for drivers (root cause), complications, and barriers Advise Advise on obesity risks (related more to obesity stage than BMI) Explain benefits of modest weight loss focusing on improving health & wellbeing Explain need for long-term strategy Discuss treatment options Agree Agree on realistic weight-loss expectations Agree on treatment plan Assist Address drivers and barriers Provide education and resources Refer to appropriate provider Arrange follow-up

28. Talk to Rosalia using the 5 As of obesity management Ask: “Let’s talk about your exam. Your mammogram is normal and your exam, and most of your tests are fine. But your blood sugar and A1c are higher than we like to see. This is pre- diabetes. The single best thing you could do for your health would be to make some lifestyle changes that produce some weight loss. Is today a good time to talk about your weight?” Rosalia: “Yes, we can talk about it. I know I need to lose weight – at least 80 pounds. I don’t want to end up like my father.” You: I’m glad to hear you are taking this seriously. We can talk about a goal later, but the good news is that you can improve your diabetes risk with 11-22 pounds loss. Let me ask you a few questions to get started.” What if she says, “No”? Assess: Comorbidities (sleep apnea symptoms, depression symptoms) Drivers of weight gain (medications including OTC; sleep deprivation, stress) Complications and Barriers to weight loss success. Current lifestyle. What has worked in the past. What hasn’t worked in the past.

29. Motivational interviewing (OARS Strategy) O Open-ended questions Ask open-ended questions that encourage thought- provoking response Engage in a 2-way dialogue Goal is to understand a patient’s barriers and expectations S Summary statements Use statements that recount and clarify the patient’s statements Identify specific points to act upon A Affirmative statements Recognize and support the patient’s personal strengths, successes, and efforts to change Goal is to promote a collaborative relationship R Reflections Use reflective listening Respond thoughtfully by paraphrasing Confirm that the patient has been heard Validate the patient’s point of view

30. Talk with Rosalia using OARS motivational interviewing strategy Clinician (you): You mentioned 80 pounds, but losing 11-22 pounds and even as little as 8 pounds can reduce your risk. How do you feel about that statement? Or, “What are some of your thoughts on losing weight?" Health is the right reason to make lifestyle changes. You CAN decrease your diabetes risk. Regaining weight is the result of our bodies’ natural defenses. It’s not your fault. It sounds like you are saying you need some help with maintaining lost weight. What do you think about that? That’s one option we can discuss for our long term strategy. I’m hearing that you’ve struggled with weight and recognize how it is affecting your health and quality of life. Ok. Now, let’s discuss some strategies to develop a long-term plan to help you address your concerns Rosalia: I know I can do it because I have done it before. With Weight Watchers online once. I lost 10 pounds in 3 months. I also did Jenny Craig with even more weight loss. I know I will never be skinny, but I want to be healthy and be around for my kids. Yes, but I can’t keep it off, so I wasn’t successful. Yes. I don’t think I can do it without help. I might need something. What about medication? OK! O A R S Open-ended Affirmative Reflections Summary

31. Talking to patients about weight: Patient-centered communication Keys to Successful Conversations Preventing Weight Bias. Module 2: Helping Without Harming in Clinical Practice. The Rudd Center for Food Policy and Obesity. Yale University. Choose words carefully: “Healthy eating habits” not “diet” “Physical activity routine” not “exercise” “Weight” or “healthy weight” not “fat” or “fatness” Other terms to avoid: “excess fat,” “heaviness,” “large size,” “weight problem” Listen actively, with empathy and encouragement Be non-judgmental

32. Summary Ask Ask for permission to discuss weight Explore readiness for change Assess Assess obesity class and stage Assess for drivers (root cause), complications, and barriers Advise Advise on obesity risks (related more to obesity stage than BMI) Explain benefits of modest weight loss focusing on improving health & wellbeing Explain need for long-term strategy Discuss treatment options Agree Agree on realistic weight-loss expectations Agree on treatment plan Assist Address drivers and barriers Provide education and resources Refer to appropriate provider Arrange follow-up Vallis M, et al. Can Fam Physician. 2013;59:27-31; ​ Meriwether RA, et al. Am Fam Physician. 2008;77(8):1129-3. ​

33. What is the first thing you should do when discussing weight with patients? A.Recommend a diet. B.Ask permission to discuss weight. C.Ask about their exercise routines. D.Explain a high BMI's health risks.

34. STEP 2: Manage obesity with a toolbox of options Guidelines on Pharmacologic Management of Obesity

35. When should you consider an obesity medication for patients? A.To help a patient better adhere to a healthy-eating plan B.To help a patient who has lost weight with healthy eating habits and physical activity keep the lost weight off C.To help a patient lose more weight than they might lose on their own D.All of these

36. Diet and Lifestyle 1 Gastric Band 2 Gastric Bypass or Sleeve 2 Lifestyle plus Obesity Medications Patients with low risk should have lower intensity, lower risk approaches. Higher risk approaches are justified when patients have more complicated obesity. 1. Jensen et al. Circulation 2014;129(25 Suppl 2):S102-38; 2. Courcoulas et al. JAMA 2013;310:2416-2425; 3. LABS consortium. N Engl J Med 2009;361:445-54. From LABS 3 : Perioperative DVT, thromboembolism or death 1% for gastric band 5% for bypass Weight management intensification options 0%3%8%32% Mean Weight Loss 16% 12%

37. Apovian C, Aronne LJ, et al. J Clin Endocrinol Metab. 2015 2015 Feb;100(2):342-62. Pharmacological Management Of Obesity: An Endocrine Society Clinical Practice Guideline January 15, 2015

38. Common Medications for Chronic Diseases Associated with Weight ? represents uncertain/under investigation. Apovian CM, et al. J Clin Endocrinol Metab. 2015;100:342-62 Weight Gain Associated With Use Alternatives (Weight Reducing in Parentheses) DiabetesInsulin, sulfonylureas, TZDs, mitiglinide, sitagliptin? (Metformin), (acarbose), (miglitol), (pramlintide), (exenatide), (liraglutide), (SGLT-2 inhibitors) Hypertension medicationsα-Blocker?, β-blocker?ACE inhibitors?, calcium channel blockers?, angiotensin-2 RAs Antidepressants and mood stabilizers Amytriptyline, doxepin, imipramine, nortriptyline, trimipramine, mirtazapine, fluoxetine?, sertraline?, paroxetine, fluvoxamine (Bupropion), nefazodone, fluoxetine (short term), sertraline < 1 year Oral contraceptivesProgestinsBarrier methods, intrauterine devices

39. Who Qualifies for Obesity Medications? We need obesity medications to: help patients better adhere to their dietary plan help more patients achieve meaningful weight loss produce more weight loss so that health benefits will be greater help patients sustain lost weight Recommendation: Prescribe as an adjunct to diet, exercise and behavior modification for individuals: with BMI 30+; or 27+ with comorbidity; who are unable to lose and successfully maintain weight; and who meet label indications. 1     * Strong recommendation based on High quality evidence Apovian CM et al. J Clin Endocrinol Metab, February 2015, 100(2):34

40. Where obesity treatments work: Gut hormone and neuroendocrine targets FDA approved drugs Naltrexone/Bupropion Liraglutide 3 Mg Phentermine/ Topiramate Lorcaserin Orlistat Mendieta-Zero´n H, Lo´pez M, Die´guez C. Gen Comp Endocrinol. 2008 Feb 1;155(3):481-95. doi: 10.1016/j.ygcen.2007.11.009. Epub 2007 Nov 21. LAGB surgery Stomach Fat Metabolism Drugs (Beloranib) Adipose Tissue Appetite Suppressing Drugs Hypothalamus Lipase Inhibitors (Orlistat) Intestines Vagal Blocking Device Vagus nerve Gastric Bypass, BPD Gastric Sleeve surgeries Intestines

41. FDA-approved medications and how they work http://www.accessdata.fda.gov/scripts/cder/drugsatfda/http://www.accessdata.fda.gov/scripts/cder/drugsatfda/ AgentActionApproval Scheduled drug PhentermineSympathomimetic agentApproved, short term use, 1956 Yes Orlistat Xenical®, Alli® Pancreatic lipase inhibitorApproved, 1997No Lorcaserin Belviq® 5-HT2C serotonin agonist Little affinity for other serotonergic receptors Approved 2012Yes Phentermine/Topiramate ER Qsymia™ Sympathomimetic Anticonvulsant (GABA receptor modulator carbonic anhydrase inhibitor, glutamate antagonist) Approved 2012Yes Naltrexone SR/Bupropion SR Contrave® Opioid receptor antagonist Dopamine/noradrenaline reuptake inhibitor Approved 2014No Liraglutide 3.0 mg Saxenda® GLP-1 receptor agonistApproved 2014No

42. Medications approved for chronic weight management – safety and tolerability All data from product label AgentSafetyContraindicationsTolerability OrlistatWarning: ↑cyclosporine exposure; rare liver failure; multivit advised Chronic malabsorption; gall bladder disease All the symptoms of steatorrhea (fatty discharge, etc.) LorcaserinWarnings: serotonin syndrome; valvular heart disease; cognitive impairment; depression; hypoglycemia; priapism Do not use with MAOIs. Use with “extreme caution” with serotonergic drugs (SSRIs, SNRIs); Pregnancy Headache, dizziness, fatigue Phentermine/ Topiramate ER Warning: fetal toxicity; acute myopia; cognitive dysfunction; metabolic acidosis; hypoglycemia Glaucoma; hyperthyroidism; MAOIs; Pregnancy Paresthesias, dysgeusia; dizziness, dry mouth Naltrexone SR/ Bupropion SR Boxed warning: suicidality; Warning: BP, HR; ↑ seizure risk; glaucoma; hepatotoxicity Seizure disorder; uncontrolled HTN; chronic opioid use; MAOIs; Pregnancy Nausea, vomiting, headache, dizziness, insomnia Liraglutide 3 mg Boxed warning: rodent thyroid c-cell tumors. Warnings: acute pancreatitis, acute gallbladder disease, hypoglycemia, heart rate increase; renal impairment; suicidal behavior Patients with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia.; Pregnancy Nausea, vomiting, diarrhea, constipation, dyspepsia, abdominal pain.

43. Orlistat Two forms Alli 60mg (OTC) and Xenical 120mg (Rx) Should be taken three times daily prior to meals in conjunction with reduced calorie diet Meals should contain <30% fat to decrease risk of GI side effects Side effects are mostly GI: abdominal pain, nausea, oily stools. Fecal urgency, flatus with discharge Has been used out to 4 years Drug interactions: cyclosporine, fat-soluble vitamin, levothyroxine, warfarin, amiodarone, antiepileptic drugs (mostly due to decreased absorption) Reversible inhibitor of gastric lipase – unable to hydrolyze dietary fats and triglycerides into absorbable free fatty acids and monoglycerides Mean percentage weight loss (treated vs placebo) at one year was 3% (13.4 lbs vs 5.8 lbs)

44. Lorcaserin (Belviq®) Serotonin 2C receptor agonist acting in the hypothalamus to promote satiety and decrease food consumption Dose is 1mg twice daily – discontinue use if 5% weight loss not achieved by week 12 Safety with other serotonergic or antidopaminergic drugs has not been established – concern for Serotonin Syndrome or Neuroleptic Malignant Syndrome Side effects: headache, dizziness, fatigue, nausea, dry mouth, constipation Potential drug interactions: Serotonergic drugs (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), triptans, bupropion, dextromethorphan, St. John’s Wort): use with extreme caution due to the risk of serotonin syndrome Used in conjunction with reduced calorie diet Weight loss at 52 weeks vs placebo: 5.8 kg vs 2.5 kg. % of patients losing >5% of body weight: 47.1% vs 22.6%. % of patient losing >10% body weight: 22.4% vs 8.7%

45. Phentermine/Topiramate (Qsymia®) Phentermine – sympathetic amine – release of catecholamines in the hypothalamus resulting in reduced appetite Topiramate – MOA for weight loss unknown, but augments the activity of gamma-aminobutyrate, modulates voltage-gated ion channels, inhibits glutamate receptors, inhibits carbonic anhydrase Adverse effects and contraindications are specific to the components of the drugs: CI: pregnancy, glaucoma, hyperthyroidism, during or within 14 days of using MAOI, known hypersensitivity Adverse effects: fetal toxicity, elevation in heart rate, suicidal behavior and ideation, mood and sleep disorders, cognitive impairment, metabolic acidosis Others: paresthesias, dysgeusia Four dosing options: 3.75mg/23mg, 7.5mg/46mg, 11.5mg/69mg, 15mg/92mg – the 3.75/23mg and 11.5/69mg doses are used for titration only Start 3.75/23mg daily for 14 days, then titrate to 7.5/46mg – if weight loss <3% at 12 week, then titrate again. 11.5/69 for 14 days then increase to 15/92mg. If not achieved at least 5% weight loss at 12 weeks, discontinue medication. Used in conjunction with reduce calorie intake and increased physical activity Weight reduction (% change from baseline) 7.8 - 10.9 vs placebo 1.2-1.6 Patients losing >5% body weight: 62-70% vs 17-21% Patients losing > 10% body weight: 37-48% vs 7%

46. Naltrexone 8mg/Buproprion 90mg Extended Release (Contrave®) MOA: effects on two separate areas of the brain involved in the regulation of food intake: the hypothalamus (appetite regulatory center) and the mesolimbic dopamine circuit (reward system). Adverse effects and contraindications are specific to the components of the drugs Contraindications: Uncontrolled hypertension, Seizure disorders, anorexia nervosa or bulimia, or undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs; Chronic opioid use; During or within 14 days of taking monoamine oxidase inhibitors (MAOI), pregnancy Adverse effects: Most common adverse reactions (greater than or equal to 5%): nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth and diarrhea Dose must be titrated up over 4 weeks: once daily x 1 week, twice daily x 1 week, 2 pills in the am, one in the pm x 1 week, 2 twice daily Used in conjunction with reduce calorie intake and increased physical activity Weight reduction vs placebo (% change from baseline): 3.7-8.1 vs 1.3-4.9 % Patients losing >5% body weight vs placebo: 36-57 vs 17-43 % Patients losing >10% body weight vs placebo: 15-35 vs 5-21

47. Liraglutide (Saxenda®) Liraglutide approved for adjunctive treatment of diabetes, however, when used for weight management, the dose is higher – goal dose is 3mg daily Same adverse effects and contraindications when used for diabetes: Contraindications: Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2, Pregnancy Adverse effects: nausea, hypoglycemia, diarrhea, constipation, vomiting, headache, decreased appetite, dyspepsia, fatigue, dizziness, abdominal pain, and increased lipase Dosing is once again higher – initiate dose at 0.6mg daily and titrate up by 0.6mg weekly GLP-1 is a physiological regulator of appetite and calorie intake, and the GLP-1 receptor is present in several areas of the brain involved in appetite regulation Weight changes vs placebo (% change from baseline): 4.9-7.4 vs 0.3-3 % Patients losing >5% body weight vs placebo: 44-62 vs 16-34 % Patients losing >10% body weight vs placebo: 22-33 vs 5-15

48. SNRI, serotonin–norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; MAOI monoamine reuptake inhibitor; BP blood pressure HR heart rate; http://www.accessdata.fda.gov/scripts/cder/drugsatfda/http://www.accessdata.fda.gov/scripts/cder/drugsatfda/ Weight loss effects and effects independent of weight loss AgentWeight loss-related Weight loss independent – positive Weight loss independent – negative Orlistat ExpectedIndependent effect on ↓ LDL cholesterol Reduction in fat soluble vitamin levels Lorcaserin Expected? Independent effect on glycemia- Phentermine/ Topiramate ER Expected-- Naltrexone SR/ Bupropion SR Expected; Except less than expected reduction in pulse, BP -Less than expected decrease in BP and pulse Liraglutide 3 mg Expected; Except increased pulse Independent effect on glycemiaIncrease in lipase, uncertain significance

49. Orlistat 1,2 120 mg TID 52 weeks Lorcaserin 5,6 10 mg BID 52 weeks PHEN/TPM 9,10 7.5/46 mg ER QD 56 weeks Liraglutide 7,8 3.0 mg QD 56 weeks Naltrexone/bupropion 3,4 32/360 mg ER QD 56 weeks Percent weight loss at one year NOTE: These are not head-to-head comparisons; populations differ across studies and lifestyle intervention differs across studies. Values are placebo-subtracted and approximated from kg weight reductions where applicable 1. Torgerson et al. Diabetes Care 2004;27:155–61; 2. Berne et al. Diabet Med 2005;22:612–8; 3. Smith et al. N Engl J Med 2010;363:245–56; 4. O’Neil et al. Obesity 2012;20:1426–36; 5. Apovian et al. Obesity (Silver Spring) 2013;21:935–43; 6. Hollander et al. Diabetes Care 2013;36:4022–9; 7. Pi-Sunyer et al. Diabetologia 2014;57:73-OR; 8. Davies et al. Diabetologia 2014;57:39-OR; 9. Gadde et al. Lancet 2011;377:1341–52; 10. Garvey et al. Diabetes Care online September, 2014 Placebo-subtracted weight loss in patients with and without T2DM

50. McCullough PA, et al. Poster AANP 2013. Weight loss: Individual variation

51. NOTE: These are not head-to-head comparisons; patient populations differ across studies and lifestyle interventions differ across studies. 1. Torgerson et al. Diabetes Care 2004;27:155–61; 2. Smith et al. N Engl J Med 2010;363:245–56; 3. Astrup, et al. Int J Obes (Lond) 2012; 843-854. 4. Greenway, et al. Lancet 2010; 595-605. 5. Wadden, et al. Obesity (2011) 19, 110–120. 6. Gadde et al. Lancet 2011;377:1341–52 Proportion (%) achieving 5% weight loss after 52 weeks at top dose Percentage (%) Orlistat 1 120 mg TID Lorcaserin 2 10 mg BID PHEN/TPM 6 7.5/46 mg ER QD Liraglutide 3 3.0 mg QD Naltrexone/bupropion 4 32/360 mg QD Naltrexone/bupropion 5 32/360 mg - BMOD

52. NOTE: These are not head-to-head comparisons; patient populations differ across studies and lifestyle interventions differ across studies. 1. Torgerson et al. Diabetes Care 2004;27:155–61; 2. Smith et al. N Engl J Med 2010;363:245–56; 3. Astrup, et al. Int J Obes (Lond) 2012; 843-854. 4. Greenway, et al. Lancet 2010; 595-605. 5. Wadden, et al. Obesity (2011) 19, 110–120. 6. Gadde et al. Lancet 2011;377:1341–52 Proportion (%) achieving 10% weight loss after 52 weeks at top dose Percentage (%) Orlistat 1 120 mg TID Lorcaserin 2 10 mg BID PHEN/TPM 6 7.5/46 mg ER QD Liraglutide 3 3.0 mg QD Naltrexone/bupropion 4 32/360 mg QD Naltrexone/bupropion 5 32/360 mg - BMOD

53. Developing a treatment plan for Rosalia Advising on treatment options You advised Rosalia that losing at least 5% of weight loss in the next 12 weeks is, for now, a good goal. You reviewed medications and other drivers of weight gain (acetominophen PM, paroxetine). Rosalia asked about weight-loss medication and you discussed the available options. Agreeing on weight goals and treatment plan* Rosalia will attend weekly Weight Watchers meetings because her office wellness program offers it. Instead of eating at her desk, Rosalia will join co-workers on lunchtime walks. She sets a goal of 150 minutes per week of brisk walking. Rosalia will adopt a low-glycemic index diet in the Weight Watchers program after a visit with a dietitian. Together, you make a decision to taper and discontinue paroxetine and to discontinue acetaminophen PM. Rosalia will monitor sleep duration on her Fitbit and has engaged in meditation through a smartphone app. Rosalia begins liraglutide 0.6 mg with a dose escalation planned to 3.0 mg. Follow-up plan Refer her to a local dietician you’ve worked with in the past. Schedule follow-up visits weekly for the next 3 weeks, then monthly for the next 3 months. Check in at 12 weeks to confirm if she’s lost at least 5% of her weight. Follow at least every three months thereafter. After 6 months, renew emphasis on physical activity, trying to push to 250 minutes of moderate activity per week. Continue liraglutide.

54. Rosalia’s treatment strategy Vallis M, et al. Can Fam Physician. 2013;59:27-31; ​ Meriwether RA, et al. Am Fam Physician. 2008;77(8):1129-3. Ask Ask for permission to discuss weight Explore readiness for change Assess Assess obesity class and stage Assess for drivers (root cause), complications, and barriers Advise Advise on obesity risks (related more to obesity stage than BMI) Explain benefits of modest weight loss focusing on improving health & wellbeing Explain need for long-term strategy Discuss treatment options Agree Agree on realistic weight-loss expectations Agree on treatment plan Assist Address drivers and barriers Provide education and resources Refer to appropriate provider Arrange follow-up

55. Diet and Lifestyle 1 Gastric Band 2 Gastric Bypass or Sleeve 2 Lifestyle plus Obesity Medications Patients with low risk should have lower intensity, less risk approaches. Higher risk approaches are justified when patients have more complicated obesity. 1. Jensen et al. Circulation 2014;129(25 Suppl 2):S102-38; 2. Courcoulas et al. JAMA 2013;310:2416-2425; 3. LABS consortium. N Engl J Med 2009;361:445-54. From LABS 3 : Perioperative DVT, thromboembolism or death 1% for gastric band 5% for bypass Weight management intensification options 0%3%8%32% Mean Weight Loss 16% 12%

56. Bariatric surgery criteria BMI <18.518.5-24.925.0-29.930.0-34.935.0-39.9>40 underweightnormaloverweightobesity Iobesity IIobesity III With ≥1 severe obesity- associated comorbidity (e.g., diabetes or OSA) With no comorbidities

57. Sleeve Gastrectomy More effective weight loss than adjustable gastric banding; comparable with gastric bypass ReShape™ Integrated Dual Balloon System 2 Two attached balloons placed into stomach through mouth and inflated 25.44% EWL and 11.27% TBWL at 12 months Effectiveness and risks of bariatric surgery and devices: RESULTS Bariatric surgery 1 : Provides substantial and sustained effects on weight loss Ameliorates obesity-attributable comorbidities in most patients Risks of complication, reoperation, and death exist An Updated Systematic Review and Meta-analysis, 2003-2012 1 Change S-H, et al. JAMA Surg. 2014;149(3):275-287; 2 ASGE Bariatric Endoscopy Task Force, et al. Gastrointest Endosc. 2015 Sep;82(3):425-38.e5 3 www.fda.gov/MedicalDevices Adjustable Gastric Banding Lower mortality Lower complication rates Higher reoperation rate Less weight loss than gastric bypass Gastric Bypass More effective weight loss More complications ORBERA™ Intragastric Balloon System 3 Balloon placed into stomach through mouth and filled with saline 10.2% WL at 6 months

58. New Device AspireAssist is a surgically-placed tube to drain a portion of the stomach contents after every meal A disk-shaped port valve that lies outside the body, flush against the skin of the abdomen, is connected to the tube and remains in place. Approximately 20 to 30 minutes after meal consumption, the patient attaches the device’s external connector and tubing to the port valve, opens the valve and drains the contents. Once opened, it takes approximately five to 10 minutes to drain food matter through the tube and into the toilet. The device removes approximately 30 percent of the calories consumed. The device also has a safety feature that keeps track of the number of times the drain tube is connected to the port and automatically stops working after 115 cycles (approximately five to six weeks of therapy); patients must return for a medical visit to get a replacement part for the device in order to continue the therapy.

59. Pulmonary disease Abnormal function Obstructive sleep apnea Hypoventilation syndrome Nonalcoholic fatty liver disease Steatosis Steatohepatitis Cirrhosis Coronary heart disease Diabetes Dyslipidemia Hypertension 69% resolved Gynecologic abnormalities Abnormal menses Infertility Polycystic ovarian syndrome Osteoarthritis Skin Gall bladder disease Cancer Breast, uterus, cervix, colon, esophagus, pancreas, kidney, prostate Phlebitis 95% resolved Venous stasis Gout 72% resolved Resolution of comorbidities Idiopathic intracranial hypertension Stroke Cataracts Severe pancreatitis 41% resolved 90% reduced 74-98% resolved

60. Bariatric surgery – low mortality When performed at a Bariatric Surgery Center of Excellence

61. Putting it all together: Obesity is a complex, chronic disease Risk for obesity is driven by environmental and biologic factors in genetically susceptible individuals Moderate weight loss can improve health, but response to treatment is highly variable and weight regain is common When patients struggle, intensification of approach is appropriate Combinations of approaches (diet, exercise, drugs, devices and surgery) produce more weight loss and health benefit

62. When should you consider an obesity medication for patients? A.To help a patient better adhere to a healthy-eating plan B.To help a patient who has lost weight with healthy eating habits and physical activity keep the lost weight off C.To help a patient lose more weight than they might lose on their own D.All of these

63. STEP 3: Get reimbursed Reimbursement for Obesity Management

64. What must be documented as part of intensive behavioral therapy for obesity? A.That the patient lost at least 6.6 pounds after six months. B.That treatment was consistent with the 5A approach. C.Up to 22 IBT sessions over 12 months. D.All of these

65. Key Considerations Centers for Medicare and Medicaid Services Reimbursement of IBT for obesity Obesity is a disease and should be treated like one. If you can’t treat it like a disease, treat comorbid conditions, billed using E&M codes. Medicare Part B allows reimbursement for IBT for obesity w/some restrictions for: screening for obesity in adults using BMI; dietary (nutritional) assessment; and, intensive behavioral counseling and therapy to promote sustained weight loss through high-intensity interventions on diet and exercise. Medicare coinsurance and Part B deductible are waived. Private insurance coverage of IBT for obesity remains highly variable However, because Medicare policy exerts a major influence on the commercial health care system, which often adopts its reimbursement and coverage policies..

66. U.S. Department of Health and Human Services. Intensive Behavioral Therapy (IBT) for Obesity. Centers for Medicare & Medicaid Services, August 2012 Requirements for Medicare coverage Eligible beneficiaries Qualified primary care providers Allowable visits Allowable primary care settings BMI>30kg/m2 Competent and alert when counseling is provided Must lose 3kg (6.6lbs) during the first 6 months for continuing coverage A physician who has a primary specialty designation of family practice, general practice, geriatric medicine, internal medicine, OB/GYN, or pediatric medicine A qualified non-physician practitioner who is a certified clinical nurse specialist, nurse practitioner, or physician assistant Auxiliary personnel such as registered dieticians working for one of the provider specialty types listed above 22 IBT sessions for obesity is maximum in a 12-month period 1 face-to-face visit every week for first month 1 face-to-face visit every other week for months 2-6 1 face-to-face visit every month for months 7-12 if beneficiary loses at least 3kg (6.6lbs) during first 6 months Independent clinics Outpatient clinics Physician’s offices State or local public health clinics

67. Medical records must document all coverage requirements, including the determination of weight loss at the 6- month visit Must document treatment consistent with the 5A’s approach Stand Alone Benefit: The IBT for obesity covered by Medicare is a stand alone billable service separate from the initial preventive physical exam (IPPE) or the Annual Wellness Visit (AMV). Medicare beneficiaries may obtain IBT for obesity services at any time following Medicare Part B enrollment, including during IPPE or AMV encounter. Note: Obesity counseling is not separately payable with another visit on the same day with the exception initial physical exams, diabetes self-management and medical nutrition therapy services (code 77X), and distinct procedural services claims (modifier 59) CMS. MLN Matters MM7641. 2012. Documentation for IBT for obesity

68. Billing and coding requirements for IBT Submitting Professional Claims Report the appropriate HCPCS code and the corresponding ICD-10-CM diagnosis code in the X12 837-P (Professional) electronic claim format Include Place of Service (POS) codes to indicate where service was provided ASCA requires providers to submit claims to Medicare electronically, with limited exceptions Submitting Institutional Claims Report the appropriate HCPCS code, revenue code, and the corresponding ICD-10-CM diagnosis code in the Xl 2 837-1 (Institutional) electronic claim format Types of Bill (TOBs) Allowed for Institutional Claims: hospital outpatient, rural health clinic (RHC), federally qualitied health center (FQHC), critical access hospital (CAH) Coding and Diagnosis Information Use the Healthcare Common Procedure Coding System (HCPCS code) G0447 (face-to-face behavioral counseling for obesity) and relevant ICD- 10-DM Diagnosis Code for BMI 30.0 and over (Z68.30-Z68.39, Z68.41-Z68.45) Do not use E66.01 or E66.09 No need to add comorbid diagnoses Use preventative codes 99401-99404 mandated by ACA for follow-up and management Covered IBT can be provided “incident to” i.e., by auxiliary staff member such as NP or PA under direct supervision of physician Can be an efficient and cost-effective way to provide IBT for obesity in a busy practice setting Physicians of other specialties may be compensated for IBT if they have multiple credentials and bill under approved taxonomy codes – e.g., NP or PA Centers for Medicare and Medicaid Services

69. Billing and coding requirements for IBT Coding and Diagnosis Information Use the Healthcare Common Procedure Coding System (HCPCS code) G0447 (face-to-face behavioral counseling for obesity) and relevant ICD- 9-DM Diagnosis Code for BMI 30.0 and over (V85.30-V85.39, V85.41 ·V85.451. Do not use 278.00 or 278.01 No need to add comorbid diagnoses Use preventative codes 99401-99404 mandated by ACA for follow-up and management Covered IBT can be provided “incident to” i.e., by auxiliary staff member such as NP or PA under direct supervision of physician. Can be an efficient and cost-effective way to provide IBT for obesity in a busy practice setting Physicians of other specialties may be compensated for IBT if they have multiple credentials and bill under approved taxonomy codes – e.g., NP or PA. Centers for Medicare and Medicaid Services

70. Summary: Learning Objectives Review recent findings about the biologic regulation of eating and weight control Discuss the clinical recommendations and benefits of sustained weight loss in overweight and obese patients Apply principles of motivational interviewing and shared decision-making to improve the clinical management of obesity and promote behavioral changes Understand current guidelines for managing obesity, including the role of pharmacological therapy as an adjunct to lifestyle changes in reducing weight gain and promoting weight loss Review reimbursement options for intensive behavioral therapy (IBT) in obesity management

71. What must be documented as part of intensive behavioral therapy for obesity? A.That the patient lost at least 6.6 pounds after six months. B.That treatment was consistent with the 5A approach. C.Up to 22 IBT sessions over 12 months. D.All of these

72. Resources On the official Weight First website, you can find: Links to guidelines, papers, and studies referenced in the presentation Access to presentation slides Opportunity for AMA PRA Category 1 CME credit More information about obesity medical management WWW.TREATWEIGHTFIRST.ORG