Faculty Affiliation Enhancing the Patient-Provider Connection: Practical Strategies for Improving Outcomes Colleen M. Fairbanks, PhD in Management Licensed Clinical Health Psychologist

Provided by Integrity Continuing Education, Inc. Supported by an educational grant from Novo Nordisk Inc. 1 2

Faculty Disclosures Learning Objectives

Dr. Fairbanks has no conflicts of interest to disclose. . Analyze regional and ethnic disparities in obesity . Address patients with obesity with sensitivity and a greater understanding of this disorder’s causes, challenges, and treatments . Apply current practice guidelines to optimize screening, diagnosis, and treatment . Implement proven communication strategies, such as The 5 A’s of Obesity Counseling, to effectively engage patients in weight loss discussion . Evaluate the efficacy and safety of available and emerging pharmacologic therapies for weight loss

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Obesity is the single greatest threat to public health for this century

Obesity Prevalence and Impact —US Department of Agriculture and US Department of Health and Human Services

U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2010. 7th Edition. 5 Washington, DC: U.S. Government Printing Offices; 2010. 6

1 Overweight/Obesity Classifications Obesity in America: 2011

NIH Guidelines for Identifying Obesity Class in Adults1 BMI for Asian Category BMI Class Populations Overweight 25.0–29.9 Prevalence of 30.0–34.9 I Epidemiologic data Obesity indicate people of obesity, by 35.0–39.9 II Asian descent are at state, in 2011, Extreme obesity* ≥40 III risk for T2DM at lower according to BMI ranges.3,4 Obesity Definitions in Children/Adolescents2 the CDC’s Lower BMI cutpoints BRFSS Sex-specific BMI for age at or above _____ are recommended for of CDC growth charts Asian Americans: . 2011 the first Obesity Extreme Obesity year of BRFSS 95th percentile 120% of the 95th percentile Overweight: ≥23–<27.5 survey Obesity: ≥27.5 *“Class III extreme obesity” now the preferred terminology over “morbid obesity.” BMI, body mass index; CDC, Centers for Disease Control and Prevention; NIH, National Institutes of Health; T2DM, type 2 diabetes mellitus. BRFSS, Behavioral Risk Factor Surveillance System. 1. NIH. Obes Res. 1998;6(Suppl 2):51S-209S; 2. Hales C, Seitz AE. MMWR Morb Mortal Wkly Rep. 2018;67:966; 3. WHO. Lancet. 2004;363:157-163; 4. Hsu WC, et al. Diabetes Care. 2015;38:150-158. 7 CDC. Overweight and Obesity. https://www.cdc.gov/obesity/data/prevalence-maps.html 8

Obesity in America: 2017 A Nation Growing Larger

. Incidence of obesity has more than doubled since 19801,2 . . . And prevalence of Obesity by the Numbers: NHANES Data from 2015–20162 obesity, by Population Obesity (%) Extreme Obesity (%) state, in 2017 Adults (≥20 years) 93.3 million (39.8) 17.8 million (7.6)

Youth (2–19 years) 13.7 million (18.5) 4.2 million (5.6)

NHANES, National Health and Nutrition Examination Survey.

CDC: Overweight and Obesity. https://www.cdc.gov/obesity/data/prevalence-maps.html 9 1. Fryar CD, et al. Natl Health Stat Report. 2018;122:1-16; 2. Hales C, Seitz AE. MMWR Morb Mortal Wkly Rep. 2018;67:966. 10

A Nation Growing Larger (cont) Obesity Rates by Race/Ethnicity

Age-Adjusted Prevalence of Overweight, Obesity, and Extreme Obesity 60 Among Adults: United States 1960–2016 55 50 53 45 51 47 47 47 40 40 43 NH White 35 3837 38 38 38 30 NH Black 30 Hispanic 25 Percent* 20 Asian 20 Overweight

Percent 15 10 13 AIAN† 15 Obesity 10 Extreme Obesity 10 0 Men Women Total 5 †Prevalence of Obesity in US Adults Age ≥20 NHANES Data 2015–2016 0

*Percentages are rounded; †AIAN not included in NHANES; data from Am J Health Promot. 2010;24:246-254.

AIAN, American Indian, Alaska Native; NH, non-Hispanic. Fryar CD, et al. NCHS Health E-Stats. September 2018. https://www.cdc.gov/nchs/data/hestat/obesity_adult_15_16/obesity_adult_15_16.pdf. 11 Hales CM, et al. NCHS Data Brief. 2017;288:1-8; Slattery ML, et al. Am J Health Promot. 2010;24:246-254. 12

2 Obesity: More Than Just Appearance

T2DM CVD Cancer Others • Insulin • Dyslipidemia • Breast • Depression insensitivity • Hypertension • Colorectal • Gallbladder • Insulin resistance • Ischemic stroke • Kidney • GERD • Metabolic • Triglyceridemia • Liver • Renal disease syndrome • Non-Hodgkin • Osteoarthritis Obesity Bias, Stigma, and Empowering Patients MI lymphoma • Respiratory • Sleep apnea

Obesity’s serious sequelae: associated comorbidities and complications

CVD, cardiovascular disease; GERD, gastroesophageal reflux disease; MI, myocardial infarction.

CDC. https://www.cdc.gov/healthyweight/effects/index.html; NIH. https://www.nhlbi.nih.gov/health-topics/managing-overweight-obesity-in-adults. 13 14

Obesity: Last Socially Acceptable Prejudice The Vicious Cycle of Weight Stigma

. Irony: as obesity rates rise, so does bias and Rather than motivating Bias & discrimination toward those affected weight loss and improved Additional Discrimination Weight Gain . People with obesity often openly, publicly humiliated, or health, stigmatizing and denied services social shaming accelerates Physical & Mental weight gain and Health Outcomes – No consequences for “fat-shamers” vs outrage for those who exacerbates poor mental High-Risk, ridicule other subset populations and physical health. Health-Related . Law provides protection against discrimination for racial, Anxiety & Behaviors Internalized Depression Mobility & QOL Shame & religious, and sexual orientation minorities; women, Worthlessness aged, disabled Morbidity & Mortality – No laws against discrimination on the basis of weight Dysregulated Health Biomarkers BP, blood pressure; CRP, C-reactive protein; LDL-C, low-density (A1c, BP, CRP, lipoprotein cholesterol; QOL, quality of life. LDL-C)

Neporent L. ABC News. January 21, 2013. https://abcnews.go.com/Health/stigma-obese-acceptable-prejudice/story?id=18276788; Phelan SM, et al. J Gen Intern Med. 2015;30:1251-1258; Sutin AR, Terracciano A. Obesity (Sliver Spring). 2017;25:1183-1186; Tomiyama AJ, et al. BMC Med. 2018;16:123. 15 Tomiyama AJ, et al. BMC Med. 2018;16:123. 16

Obesity Origins: Myths vs Realities Stigma in the Healthcare Setting . Studies show clinicians believe obesity Myths1,2 Realities2-4 stereotypes1 – Many published articles documenting physician views . Obesity solely caused by . Obesity caused by complex, – Lack of self-discipline of patients with obesity as lazy, undisciplined, stupid, impaired interplay between unattractive, and unlikely to be adherent2 – Laziness and gluttony – Genetic factors – Poor food choices and lack of exercise – Endocrinologic and metabolic . PCPs/HCPs in one study rated patients with obesity a “waste physiology – Inferior education and intelligence of time” and spent 28% less time with them3 – Personal and moral failure – Behavioral and psychosocial . It’s simple: too many calories in, elements . A test of weight bias in 2,284 male and female US physicians too few calories out – Environment found strong implicit and explicit anti-fat bias in nearly all4 . It’s complicated: not a lifestyle – Bias particularly strong in the 1,046 male physicians choice – Anti-obesity attitudes even among the 221 physicians who were themselves struggling with obesity AMA: Obesity is a complex, chronic disease — it needs medical intervention5 HCPs, healthcare providers; PCPs, primary care providers/physicians. 1. Phelan SM, et al. Patient Educ Couns. 2015;98:1446-1449; 2. Tomiyama AJ, et al BMC Med. 2018;16:123; 3. Di Ciaula Agostino, et al. Eur J Intern Med. 2014;25:865-873; 4. Piaggi P, et al. J Endocrinol Invest. 2018;41:83-89; 1. Tomiyama AJ, et al. BMC Med. 2018;16:123; 2. Phelan SM, et al. Obes Rev. 2015;16:319-326; 5. Kyle TK, et al. Endocrinol Metab Clin North Am. 2016;45:511-520. 17 3. Huizinga MM, et al. J Gen Intern Med. 2009;24:1236-1239; 4. Sabin JA, et al. PLoS One. 2012;109:195701. 18

3 Stigma in Healthcare: Blame the Victim Beyond Advice: Empowering Patients

. Survey of 1,244 fourth-year medical students on Partner with the Patient to Develop a Plan their beliefs about the causes of obesity Simple goals to start: Not 100 lbs, but 5% of Strategies for overcoming body weight; Individualized physical activity barriers and setbacks

Bad Choices by Person with Obesity 28% Locate Resources with the Patient 46% Genetic/Metabolic Dysfunction Community resources for physical activity Weight loss support groups and programs 27% Choices & Genetic/Metabolic Dysfunction Independent Contributors Follow-Up Increase accountability with regular Review progress, help patient (eg, monthly) consultations problem-solve to eliminate barriers

Phelan SM, et al. Patient Educ Couns. 2015 98:1446-1449. 19 Fitzpatrick SL, et al. Am J Med. 2016;129:115.e1-115.e7. 20

Empowering Patients: Advocates for Improved Asking and Counseling: The 5 A’s Access to Care Obesity Flow Chart

Assess comorbidities known to interfere with weight loss . Obesity Action Coalition (www.obesityaction.org)* BMI >=30.0, or >=25.0 with comorbidities Specialty ASSESS (depression, sleep problems, chronic pain, stress, binge eating) Yes referral – Promotes respect and access to effective treatment No Yes options on federal and local levels

Advise weight – Works with patients to intervene with health Educate on benefits of weight loss ADVISE maintenance insurance and employers Not ready Ready – Educates against bias and for health and treatment “Let me know when you are Discuss weight loss treatment options. Consider physician ability and – Connects patients with community and local resources ready to do something about AGREE willingness to provide intensive weight loss counseling. your weight. I can help you.” . Obesity Medicine Association (www.obesitymedicine.org) – The largest organization of clinical obesity experts Physician supervision Physician-delivered intensive behavioral (physicians and other clinicians) to provide support Referral to intensive weight management program ASSIST weight loss counseling and accountability – Advocates for comprehensive, effective, and individualized treatment Evidence-based Hospital- Behavioral Assess progress regularly, follow-up on referral made – Educates clinicians about the pathophysiology of commercial Dietitian based medicine ARRANGE to other providers or programs as appropriate obesity and effective management strategies program program provider

*OAC website offers a wide variety of handouts, fact sheets, brochures, and guides for patient education. These can be found under the “Get Educated” tab, then “Public Educational Resources.” 21 Adapted from: Fitzpatrick SL, et al. Am J Med. 2016;115:115.e1-115.e7. 22

Case Study: Mary Case Study: Discussion

. 42-year-old Hispanic woman . Direct consequences of HCP bias and stigmatization – Height: 5′6″; Weight: 240 lbs – Additional weight gain – BMI: 38 (Class II obesity) – Avoidance of medical care – Comorbidity: T2DM; A1c ~7.5 – No patient-provider trust . Mary is visiting a new doctor – Weight and A1c not controlled – She avoids HCPs because they are sometimes condescending . What should this new doctor do to turn this around? – Nag her about her weight, imply she’s lazy and gluttonous . What questions should the new doctor ask? . She wants to ask for anti-obesity medication but is afraid . Should the new doctor prescribe anti-obesity medication? – Last time she asked, doctor said she had to prove she was serious by – Why or why not? losing 10 lbs before he would prescribe – What would be your concerns about prescribing anti-obesity – He told her he didn’t think she would take it as prescribed medication? – Defeated, she didn’t return for several months and in that time, gained – Which medications would you consider? even more weight

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4 Multiple Hormones and Organs Involved in Developing and Maintaining Obesity

• Ghrelin • Adipokines • GLP-1 • Proinflammatory • GIP cytokines • CCK • NEFA • OXM

• Insulin Pathophysiology: Hormonal • Amylin and Metabolic Adaptation • Excess visceral • Microbiota changes (ectopic) fat • Gut barrier dysfunction • Adiposopathy

• Beta cell burden, dysfunction, or apoptosis

CCK, cholecystokinin; GIP, glucose-dependent insulinotropic polypeptide; GLP-1, glucagon-like peptide-1; NEFA, non-esterified fatty acids; OXM, oxyntomodulin.

25 Adapted from Scheen AJ, et al. Lancet Diabetes Endocrinol. 2014;2:911-922. 26

Complex Interplay Between Biology and Fighting to Keep the Fat: Physiologic Adaptations Psychosocial Components to Weight Loss

. When eating behavior changes because of dieting… Epigenetics – Hormone activity/functionality increases or decreases •  Orexigenic hormones (appetite stimulating) Effect:  , desire for •  Anorexigenic hormones (appetite suppressing) calorie-dense foods Environment Genes – Metabolism changes •  Fat oxidation Obesity •  Cortisol •  T4 – Energy expenditure slows Culture Physiology •  Resting energy expenditure •  Non-resting energy expenditure •  Total energy expenditure Behaviors Goal: Protect the fat supplies! Result: Weight loss DEcelerates, weight gain ACCelerates…weight is regained T4, thyroxine. Bray GA, et al. Lancet. 2016;387:1947-1956. 27 Apovian CM, et al. J Clin Endocrinol Metab. 2015;100:342-362; Sumithran P, Proietto J. Clin Sci (Lond). 2013;124:231-241. 28

Key Hormones Dysregulated with Weight Gain and Regain

Hormone Normal Function Dysfunction with Weight  or  CCK Suppresses appetite Decreases during dieting and weight loss Ghrelin Stimulates appetite and desire for Increases during dieting and weight loss high-fat, high-sugar foods GIP Stores energy Increases during dieting and weight loss

GLP-1 Suppresses appetite, increases satiety Functionality decreases Insulin Regulates energy balance; signals satiety Decreases after dieting; insulin resistance to the brain develops in people with obesity Obesity Management: Current Guidelines Leptin Regulates energy balance; suppresses Decreases during weight loss and Therapy Options appetite PYY Suppresses appetite Decreases in people with obesity

PYY, peptide YY.

Sumithran P, Proietto J. Clin Sci (Lond). 2013;124:231-241. 29 30

5 Clinical Guidelines Clinical Guidelines (cont) There is no singular, universally accepted algorithm for obesity Question: 1 . AACE/ACE Is weight loss . AHA/ACC/TOS 2 . Endocrine Society effective to – Defines obesity and – Like AHA/ACC/TOS, ranks Grade A Recommendation: – Follow-up to AHA/ACC/TOS treat diabetes cardiometabolic risk based on evidence for interventions Medication-assisted weight focused on pharmacotherapy risk and loss using liraglutide, • BMI, waist circumference, • Purpose of medication is to from A (strong) to D (weak) prevent /, comorbidities ameliorate comorbidities – Focused on inter-relationship T2DM? or should be – Ranks evidence for various and enhance adherence to considered in patients at risk for future T2DM and interventions from Class I lifestyle changes between obesity and weight-related comorbidities should be used when (high benefit, low risk) to Class – Explores dosing, pros/cons Question: needed to achieve 10% III (no benefit, harmful) of the 6 FDA-approved – Organized as a series Is weight loss weight loss in conjunction • Diet/physical activity anti-obesity medications effective to with lifestyle therapy. of questions with treat HTN? • Behavior/lifestyle – Discusses patient selection • Pharmacotherapy/surgery evidence-based responses and individualizing therapy Grade A Recommendation: – Algorithm to determine when and recommendations Patients with HTN should be treated with – Recommends GLP-1 analog or pharmacotherapy and surgery lifestyle therapy to achieve 5%–15% SGLT2 for obesity + T2DM weight loss to achieve blood pressure might be needed reduction goals.

AHA/ACC/TOS, American Heart Association/American College of Cardiology/The Obesity Society; AACE/ACE, American Association of Clinical Endocrinologists/American College of Endocrinology; HTN, hypertension. SGLT2, sodium-glucose cotransporter 2. 1. Jensen MD, et al. Circulation. 2014;129(Suppl 2):S102-S128; 2. Apovian CM, et al. J Clin Endocrinol Metab. 2015;100:342-362 31 Garvey WT, et al. Endocr Pract. 2016;22(Suppl 3):1-203. 32

AHA/ACC/TOS Treatment Algorithm AHA/ACC/TOS Treatment Algorithm (cont)

High-intensity comprehensive lifestyle Follow-up and Measure BMI 25-29.9 (overweight) Assess and treat risk Assess weight intervention Patient Yes weight loss Yes, ready weight, height; or 30-34.9 (Class I obese) factors for CVD and and lifestyle Encounter or 35-35.9 (Class II obese) BMI ≥25 obesity-related maintenance calculate BMI histories Alternative or ≥40 (Class III obese) comorbidities delivery of lifestyle Determine weight loss No intervention and health goals and Yes BMI 18.5-24.9 intervention strategies Evaluation Assess need to Intensive behavioral Yes lose weight: treatment; reassess and No, insufficient risk BMI ≥30 or Weight loss ≥5% address medical or other Weight loss ≥5% Measure weight Advise to avoid contributory factors; Comprehensive lifestyle and calculate BMI weight gain; BMI 25-29.9 with and sufficient and sufficient Treatment risk factor(s) consider adding or No intervention alone or with annually or more address and treat improvement in reevaluating obesity improvement in adjunctive therapies frequently other risk factors Yes health targets pharmacotherapy, and/or health targets (BMI ≥30 or ≥27 with refer to an experienced comorbidity) bariatric surgeon No Assess readiness to make lifestyle No, not yet ready changes to achieve Continue intensive BMI ≥40 or BMI ≥35 with weight loss medical management of BMI ≥30 or BMI ≥27 with comorbidity. Offer referral to an CVD risk factors and comorbidity—option for adding experienced bariatric surgeon for obesity-related pharmacotherapy as an adjunct to Yes, ready consultation and evaluation as an conditions; weight comprehensive lifestyle adjunct to comprehensive lifestyle management options intervention intervention

Adapted from: Jensen MD, et al. Circulation. 2014;129(Suppl 2):S102-S128. 33 Adapted from: Jensen MD, et al. Circulation. 2014;129(Suppl 2):S102-S128. 34

AACE Algorithm: Identifying Obesity Patients at AACE Algorithm: When to Start Anti-Obesity Increased Health Risk Medications

Initiate Lifestyle Therapy Initiate Anti-Obesity Medications Screening Annual BMI

No Complications Lifestyle Therapy Failure Patients with overweight/obesity who have Add medication for patients with BMI ≥30 with no no significant weight-related complications weight-related complications or with BMI ≥27 with ≥1 weight-related complications. Diagnosis • BMI ≥25 kg/m2 • BMI ≥25 kg/m2 (eg, T2DM, hypertension, CVD). (Anthropometric • BMI ≥23 kg/m2 for • BMI ≥23 kg/m2 for Weight Regain on Lifestyle Therapy Component) some ethnicities some ethnicities Add medication for patients who continue to gain weight Mild to Moderate Complications or whose weight-related complications have not Patients with overweight/obesity who have improved or who experience weight regain despite initial mild to moderate weight-related success on lifestyle therapy alone. complications but for whom lifestyle therapy 1. Clinical interpretation of BMI: Ensure elevated BMI is indicative of is expected to yield sufficient weight loss to Presence of Weight-Related Complications excess adiposity by assessing: age, gender, muscularity, hydration resolve complications. Anti-obesity Start anti-obesity medication and lifestyle therapy status, edema, third space fluid collection, large tumors, sarcopenia Clinical medication can also be started based on simultaneously for patients who have weight-related 2. Waist circumference if BMI <35 kg/m2: Adds information pertaining Component of clinical judgment. complications, particularly if severe. to cardiometabolic disease risk; use gender- and ethnicity-specific Diagnosis cut-off values 3. Can consider using body composition technologies

Garvey WT, et al. Endocr Pract. 2016;22(Suppl 3):1-203. 35 Adapted from: Garvey WT, et al. Endocr Pract. 2016;22(Suppl 3):1-203. 36

6 FDA-Approved Anti-Obesity Medications FDA-Approved Anti-Obesity Medications (cont)

Agent (Trade Name) MOA % Use with Caution in Agent (Trade Name) MOA % Use with Caution in Year Approved Route TBWL* Contraindications Patients with/Monitor for Year Approved Route TBWL* Contraindications Patients with/Monitor for Liraglutide (Saxenda®) • GLP-1 RA 5.2% • Personal or family history of • Pancreatitis + • Opiate 4.1% • Uncontrolled HTN • Suicidal ideation 2014† • SC injection MTC or MEN2 • Acute gallbladder disease antagonist + • Seizure disorders • Depression • • Cholelithiasis (Contrave®) DA and NE • Anorexia or bulimia • Psychiatric disorders • Suicidal ideation 2014 reuptake • Alcohol withdrawal • Concomitant use of MAOI Inhibitor • Opioid abuse • Liver dysfunction Most Common AEs (≥5%): Patients without T2DM: headache, dizziness, fatigue, nausea, dry mouth, • Oral • Pregnancy • Concomitant use of OADs† Patients with T2DM: hypoglycemia, headache, back pain, cough, fatigue (Belviq®, • Serotonin RA 3.3% • Serotonin syndrome • Concomitant use of SSRI, Most Common AEs (≥5%): nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, Belviq XR®) • Oral • Neuroleptic malignant SNRI, MAOI Orlistat (Xenical®, • Lipase inhibitor 3% • Chronic • Liver dysfunction‡ 2012 syndrome • Cardiac valve disease Alli®– OTC) • Oral syndrome • Renal impairment • Pregnancy • Depression 1999 • Cholestasis • Malabsorption of • Pregnancy fat-soluble vitamins Most Common AEs (≥5%): Patients without T2DM: headache, dizziness, fatigue, nausea, dry mouth, constipation Patients with T2DM: hypoglycemia, headache, back pain, cough, fatigue Most Common AEs (≥5%): Oily spotting, flatus with discharge, fecal urgency, fatty/oily stool, oily evacuation, increased defecation, fecal incontinence

*Average TBWL compared with placebo in clinical trials; all percentages taken from package insert with maximum *Average TBWL compared with placebo in clinical trials; all percentages taken from relevant package insert with maximum number cited; †Liraglude number cited; †Weight loss may cause hypoglycemia in paents taking drugs for diabetes; ‡Rare cases of severe liver originally approved in 2010 at a lower dose range and under a different trade name, for type 2 diabetes. injury have been reported. AEs, adverse events; MEN2, multiple endocrine neoplasia type 2; MTC, medullary thyroid carcinoma; MAOI, monamine oxidase inhibitor; MOA, mechanism of action; RA, receptor agonist; SC, subcutaneous; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TBWL, total body weight loss. DA, dopamine; NE, norepinephrine; OADs, oral antidiabetic drugs; OTC, over the counter.

Belviq® PI 2017; Apovian CM, et al. J Clin Endocrinol Metab. 2015;100:342-362; Garvey WT, et al. Endocr Pract. 2016;22(Suppl 3):1-203; Apovian CM, et al. J Clin Endocrinol Metab. 2015;100:342-362; Contrave® PI 2017; Garvey WT, et al. Endocr Pract. 2016;22(Suppl 3):1-203; Saxenda® PI 2018. 37 Xenical® PI 2015. 38

FDA-Approved Anti-Obesity Medications (cont) Individualizing Pharmacotherapy

Agent (Trade Name) MOA % Use with Caution in AACE/ACE: To select optimal anti-obesity medication for an Year Approved Route TBWL* Contraindications Patients with/Monitor for individual patient, consider differences in efficacy, side Phentermine + • NE-releasing 9.4% • Hyperthyroidism • Suicidal ideation effects, and cautions and warnings, as well as the presence of Topiramate ER agent; CNS • Glaucoma • Depression weight-related complications and medical history.1 (Qsymia®) + • Recent use of MAOI • Mood and sleep disorders 2012 GABA receptor • Pregnancy • Increased heart rate . CVD: Orlistat, lorcaserin, and liraglutide are preferred.* The combination of phentermine/topiramate is not agonist • Cognitive impairment contraindicated in CVD but should be used with caution with monitoring of heart rate and rhythm. • Oral • Concomitant use of OADs† . Depression: Naltrexone/bupropion and lorcaserin should be used with caution after careful review of concomitant antidepressants. Orlistat, liraglutide, and phentermine/topiramate may be considered. When Most Common AEs (≥5%): paresthesia, dizziness, dysgeusia, insomnia, constipation, dry mouth possible, weight-neutral antidepressants should be chosen. Phentermine‡ • NE-releasing N/A • Cardiovascular disease • Anxiety disorders . CKD: All anti-obesity medications can be used with caution in patients with mild renal impairment. The (Adipex-P, Suprenza) agent; CNS • Hyperthyroidism • Uncontrolled hypertension combinations of naltrexone/buproprion and phentermine/topiramate can be used in low doses in moderate 1959 stimulant • Glaucoma • History of drug abuse impairment, but should not be used in patients with severe impairment. Liraglutide and orlistat can be • Pregnancy • History of seizures considered in ESRD with a high level of caution. Most Common AEs (≥5%): Headache, increased BP and HR, tachycardia, palpitations, dry mouth, dysgeusia, insomnia, . Seizure disorder: Avoid naltrexone/bupropion in this population. Phentermine/topiramate, lorcaserin, anxiety, constipation liraglutide, and orlistat are preferred. * Average TBWL compared with placebo in clinical trials; all percentages taken from package insert with maximum number cited; †Weight loss may cause hypoglycemia in paents taking drugs for diabetes; ‡Approved for short-term *Liraglutide for obesity (3 mg) has demonstrated no increased risk for CVD based on the LEADER trial, which looked use ≥3 months. at CVD risk in individuals with T2DM as well as in established CVD on a 1.8 mg dose of liraglutide.2

CNS, central nervous system; ER, extended release; GABA, γ-aminobutyric acid; HR, heart rate. CKD, chronic kidney disease; ESRD, end-stage renal disease; LEADER, Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results. Adipex-P® PI 2012; Apovian CM, et al. J Clin Endocrinol Metab. 2015;100:342-362; Garvey WT, et al. Endocr Pract. 2016;22(Suppl 3):1-203; Qsymia® PI 2018; Suprenza® PI 2013. 39 1. Garvey WT, et al. Endocr Pract. 2016;22(Suppl 3):1-203; 2. Marso SP, et al. N Engl J Med. 2016;375:311-322. 40

Individualizing Pharmacotherapy (cont) New and Emerging Treatments: Gelesis100

Endocrine Society: Diet, exercise, and behavioral modification 1 should be included in all obesity management approaches. . A hydrogel-filled capsule ingested orally, gelesis100 (Plenity™) is NOT a drug Patients who have a history of being unable to successfully – Approved by FDA in April 2019 as a device lose and maintain weight and who meet label indications are candidates for anti-obesity medications. – Contraindicated or to be avoided in patients who are pregnant or who have . T2DM: Liraglutide or other GLP-1 analogues or SGLT2 inhibitors should be chosen due to the dual benefit certain GI conditions of these agents in glucose regulation and weight-negative profiles. Clinicians should use weight-losing . After swallowing, hydrogel expands to fill the stomach, producing feelings of or weight-neutral medications in the management of T2DM patients who are affected by obesity. For patients who use insulin, consider adding , pramlintide, or a GLP-1 analogue to mitigate against weight gain. fullness . Psychiatric disorders: Clinicians should choose weight-neutral antipsychotics when indicated over those – Gel passes through GI system naturally known to cause weight gain. – Has no caloric value . Contraception: Recommend oral contraceptives over injectables due to weight gain potential with injectables. . Approved for adults with BMI 25–40 based on results from GLOW trial2 – Phase 3 trial in 436 patients • 59% of patients achieved weight loss of ≥5% vs 42% taking placebo • 27% achieved ≥10% weight loss vs 15% in placebo group

Apovian CM, et al. J Clin Endocrinol Metab. 2015;100:342-362. 41 1. Business Wire. April 14, 2019. https://www.businesswire.com; 2. Greenway FL, et al. Obesity. 2019;27:205-216. 42

7 Anti-Obesity Medications in Phase 3 Trials Using ADAPT in Conversations

Name Study ID # Total No. Step Goal Things to Say (Drug Class) (Acronym) Pts Enrolled Study Populations A: Attitude Overcome attitudes of “I know you feel stuck; a lot of people feel that discouragement or defeat way when they think about trying to lose 5,510 • Adults with BMI ≥30 or ≥27 + ≥1 Semaglutide NCT03548935 (STEP 1) weight. Let’s see if we can come up with a (GLP-1 RA) NCT03552757 (STEP 2) weight-related comorbidity (ie, HTN, way to get you unstuck.” NCT03611582 (STEP 3) DYS, OSA, CVD) NCT03548987 (STEP 4) • Adults with BMI ≥27 + T2DM D: Defining the Identify barrier(s) to weight loss “What do you think is the biggest obstacle NCT03693430 (STEP 5) • Adults with BMI ≥27 + ≥2 problem preventing you from losing weight?” NCT03811574 (STEP 6) weight-related comorbidities or A: Alternative Come up with alternative ways to “What are some possible solutions to this • BMI ≥35 + 1 weight-related solutions overcome the barriers problem?” “Which solution do you think comorbidity would be the most effective?” “Which solution are you willing to try in the next week?” Dapagliflozin NCT02338193 (DAPA-GDM)* 264 • Women with Class I, II, or III obesity (SGLT2) NCT02635386† + PCOS P: Predicting Consider possible consequences of “What things could prevent you from trying NCT03419624† • Women with overweight or obesity consequences the proposed solutions and decide this solution?” “What might happen if you which solution is best tried the solution this week?” (BMI ≥25) + recent GDM • Adults with BMI ≥30 + T2DM with high T: Trying the Trying the solutions and evaluating “Name a day and time you will attempt this A1c (ie, ≥8%–11%) solution their efficacy solution in the next week.”

*Obesity the primary outcome measure; †Obesity a secondary outcome measure. ADAPT, Attitude, Defining the problem, generating Alternative Solutions, Predicting consequences, DYS, dyslipidemia; GDM, gestational diabetes mellitus; OSA, obstructive sleep apnea; PCOS, polycystic ovary syndrome. Trying the solution.

Source: ClinicalTrials.gov using filters for “obesity,” “interventional studies,” “recruiting,” “active, not recruiting,” and “phase 3.” 43 Adapted from: Fitzpatrick SL, et al. Am J Med. 2016;115:115.e1-115.e7. 44

Summary

. Prevalence of obesity and extreme obesity has more than doubled since 1980 – Adds tremendous disease burden from weight-related comorbidities and complications . Clinicians often regard obesity as a character flaw, instead of a disease that needs medical treatment – Studies reveal explicit and implicit bias against patients with obesity, yielding inadequate medical care – Few clinicians recognize the complex pathophysiologic, metabolic, and psychosocial components involved in etiology . Obesity can be successfully managed using – The 5 A’s of Obesity Counseling – Recent clinical guidelines – Empathetic, nonjudgmental language and approach – Anti-obesity medications as well as lifestyle interventions 45

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