3 Steps to Successful Obesity Management

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 Association of Nurse Practitioners and the Endocrine Society • Developed by Knighten Health. • Supported by an unrestricted education grant from Novo Nordisk Inc. • Connie Hale, DNP, APRN, FNP-BC: No relevant financial relationships with any commercial interests

4. Weight First Initiative • The Endocrine Society engaged four health care practitioners -- an internist, a family practice physician, an osteopathic practitioner, and a nurse practitioner -- in a pilot program to collaborate with faculty on the Guidelines on Pharmacologic Management of Obesity to develop a curriculum for primary care practitioners in obesity medical management best practices. • The objective of the Weight First initiative 2016 pilot is to demonstrate that an obesity curriculum co-developed by endocrinologists and primary care practitioners overcomes barriers to the effective management of patients with obesity. • The goal was to encourage primary care practitioners to treat weight first, rather than treating co-morbidities without directly addressing weight as a factor in overall health.

5. Prevalence of Obesity The “Obesity Belt”: Obesity prevalence > 30% 1 in 3 American adults are obese 31.7% Source: Prevalence of Self-Reported Obesity Among U.S. Adults: “The Obesity Belt” BRFSS, 2013 Sources: Behavioral Risk Factor Surveillance System, 2012, CDC; U.S. Census Bureau, 2012 QuickFacts

6. What are the 3 Steps to Successful Obesity Management? Step 1: Motivational Interviewing Step 2: Therapeutic options Step 3: Reimbursement

7. The case for putting weight first

8. Obesity is a complex and multifactorial disease1-6 1. Woods SC et al. Int J ObesRelatMetabDisord. 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. EndocrPract. 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. Gut microbiota Fat cells Genetics/epigenetics Expenditure Intake Energy balance Medications Environment

9. Obesity is “getting worse in this country,” rapidly Ogden CL, Carroll MD, Flegal KM. JAMA. 2014 Jul;312(2);189-90.

10. 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). Waist Circumference: Men > 40 in, Women > 35 in Disease risk relative to normal weight and waist circumference High Very High Extremely High

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

12. Obesity as an endocrine-related disease • 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. Morton GJ, Meek TH, Schwartz MW. Nat Rev Neurosci. 2014 Jun;15(6):367-78. 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 cancer • Disease results through a perturbation in the central nervous system (CNS) regulation of energy homeostasis

13. Multiple hormonal signals influence hypothalamic neurons and appetite1-3 1. Woods SC et al. Int J ObesRelatMetabDisord. 2002;26(suppl 4):S8-S10. 2.Suzuki K et al. Exp Diabetes Res. 2012;2012:824305. 3. ValassiE et al. NutrMetabCardiovasc. 2008;18:158-168. StomachGhrelin Increases appetite Suppresses appetite Appetite Fat cellsLeptin GutGLP-1, CCK, PYY PancreasInsulin, Amylin

14. 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 Mr. Jones 200 pounds needs 2000 kcal/day Loses weight to 200 pounds Needs 1830 kcal/day ↑ hunger, ↓satiety ≠ Smith Jones

15. 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 11 lbGAIN 30 lb LOSS 10 week weight-loss program

16. 14% weight loss produced changes in 8 hormones that encourage weight regain Sumithran P et al. N Engl J Med. 2011;365:1597-1604. 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 • Netresult of these hormonal changes is WEIGHT GAIN!

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

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

19. 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). Waist Circumference: Men > 40 in, Women > 35 in Disease risk relative to normal weight and waist circumference High Very High Extremely High

20. Modest weight loss has benefits, with greater weight loss associated with greater benefit

21. 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 10% weight loss = 30% VAT Loss VAT VAT SCAT SCAT Abdominal obesity, increased waist circumference After weight loss, reduced waist circumference Increased risk Lowered risk

22. 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.

23. Obesity is a disease, but are we talking about it? 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 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 • Health care provider – 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

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

25. Meet Rosalia: Working mom with a family history of type 2 diabetes • In for annual visit. • 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/m2 (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.

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)

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 Open-ended Affirmative Reflections Summary R S

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.

32. Summary Vallis M, et al. Can Fam Physician. 2013;59:27-31;​ Meriwether RA, et al. Am Fam Physician. 2008;77(8):1129-3.​

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

34. Obesity management: A chronic disease requiring life-long care Considerations for patients at different obesity stages Jensen MD, et al. Obesity. 2014;22(S2):S1-S410 Apovian CM et al. J ClinEndocrinolMetab, February 2015, 100(2):34 • Stage 0 obesity • BMI 25-30 or ≥ 30, but no complications/comorbidities • Lifestyle modification, healthy eating and physical activity • Self-directed weight loss with reduced calorie meal plan and physical activity • Follow patient for development of obesity associated risks. • Stage 1 obesity • BMI ≥ 27 with co-morbidity • Address drivers of weight gain: transition off drugs for co-morbidities that cause weight gain and eliminate other drivers of weight gain • Intensive comprehensive lifestyle intervention • Consider adding weight loss medications to lifestyle therapy program • Stage 2 obesity • BMI ≥ 40 or ≥ 35 with co-morbidity • Unsuccessful with therapies that are less intensive • Consider bariatric surgery • Discuss bariatric surgery • Refer for bariatric surgery evaluation

35. Weight management intensification options 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. Mean Weight Loss 16% 0% 3% 8% 12% 32% Lifestyle plus Obesity Medications Diet and Lifestyle1 Gastric Bypass or Sleeve2 Gastric Band2 From LABS3: Perioperative DVT, thromboembolism or death 1% for gastric band 5% for bypass

36. Best Diets to Support Weight Loss Johnston, B, Kanters, S,Bandayrel, K, Wu, P, Naji,F, Siemieniuk, R, Ball, G, Busse, J, Thorlund, K,Guyatt, G, Jansen, J, Mills, E. (2014). Comparison of weight loss among named diet programs in overweight and obese adults: A meta-analysis. JAMA, 312(9):923-933. doi:10.1001/jama.2014.10397. • Comparison of Weight Loss Among Named Diet Programs in Overweight and Obese Adults: A Meta-analysis • Over a 12 month period, low-Carbohydrate and low-fat diets were associated with more weight loss than no dietary intervention • Behavioral support and exercise enhanced weight loss • Weight loss differences between individual diets were small, and likely not significant to those seeking weight loss • Conclusion: The best diet is the one the patient will adhere to in order to lose weight

37. Where obesity treatments work: Gut hormone and neuroendocrine targets 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. Appetite Suppressing DrugsHypothalamus FDA approved drugs • Naltrexone/Bupropion • Liraglutide 3 Mg • Phentermine/ Topiramate • Lorcaserin • Orlistat Vagal Blocking Device Vagus nerve LAGB surgery Stomach Lipase Inhibitors (Orlistat) Intestines Gastric Bypass, BPD Gastric Sleeve surgeries Intestines Fat Metabolism Drugs (Beloranib) Adipose Tissue

38. Pharmacological Management Of Obesity: An Endocrine Society Clinical Practice GuidelineJanuary 15, 2015 Apovian C, Aronne LJ, et al. J ClinEndocrinolMetab. 2015 2015 Feb;100(2):342-62.

39. Common Medications for Chronic Diseases Associated with Weight ? represents uncertain/under investigation. Apovian CM, et al. J ClinEndocrinolMetab. 2015;100:342-62

40. Who Qualifies for Obesity Medications? Apovian CM et al. J ClinEndocrinolMetab, February 2015, 100(2):34 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

41. FDA-approved medications and how they work http://www.accessdata.fda.gov/scripts/cder/drugsatfda/http://www.accessdata.fda.gov/scripts/cder/drugsatfda/

42. Medications approved for chronic weight management – safety and tolerability All data from product label

43. Weight loss effects and effects independent of weight loss 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/

44. Placebo-subtracted weight loss in patients with and without T2DM 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.Apovianet al. Obesity (Silver Spring) 2013;21:935–43; 6.Hollander et al. Diabetes Care 2013;36:4022–9; 7. Pi-Sunyeret al. Diabetologia2014;57:73-OR; 8. Davies et al. Diabetologia2014;57:39-OR; 9. Gadde et al. Lancet 2011;377:1341–52; 10.Garvey et al. Diabetes Care online September, 2014 Orlistat1,2120 mg TID 52 weeks Lorcaserin5,610 mg BID52 weeks Liraglutide7,83.0 mg QD 56 weeks Naltrexone/bupropion3,4 32/360 mg ER QD 56 weeks PHEN/TPM9,107.5/46 mg ER QD 56 weeks Percent weight loss at one year

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

46. Proportion (%) achieving 5% weight loss after 52 weeks at top dose 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.Astrupet 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 Percentage (%) Orlistat1120 mg TID Lorcaserin210 mg BID Liraglutide33.0 mg QD Naltrexone/bupropion4 32/360 mg QD Naltrexone/bupropion5 32/360 mg - BMOD PHEN/TPM67.5/46 mg ER QD

47. Proportion (%) achieving 10% weight loss after 52 weeks at top dose 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 Percentage (%) Orlistat1120 mg TID Lorcaserin210 mg BID Liraglutide33.0 mg QD Naltrexone/bupropion4 32/360 mg QD Naltrexone/bupropion5 32/360 mg - BMOD PHEN/TPM67.5/46 mg ER QD

48. Developing a treatment plan for Rosalia Advising on treatment options • You advise 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.

49. 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.

50. Weight management intensification options 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. Mean Weight Loss 16% 0% 3% 8% 12% 32% Lifestyle plus Obesity Medications Diet and Lifestyle1 Gastric Bypass or Sleeve2 Gastric Band2 From LABS3: Perioperative DVT, thromboembolism or death 1% for gastric band 5% for bypass