Medical Weight Loss in the Real World

1/16/2020

Amy Warriner, MD, CCD Professor of Medicine Program Director, Endocrinology Fellowship Director, UAB Weight Loss Medicine (WLM) Division of Endocrinology Diabetes and Metabolism

Objectives

• Understand the background pathophysiology of obesity • Recognize the multi‐pronged approach necessary for successful obesity management • Review current medication options for the treatment of overweight and obesity • Recognize surgical and endoscopic treatments for obesity

Obesity as a Disease

Characteristics of a disease1: 1. Impairment of normal function of a body system 2. Has characteristic signs or symptoms 3. Results in harm or morbidity to the entity affected

1. https://www.aace.com/files/position‐statements/obesity.pdf 2. Kyle TK. Endocrinol Metab Clin North Am. 2016 September; 45(3):511‐520.

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How Obesity Causes Disease Increased expression of some hormones, suppression of others, leads to inflammation and disease

T2DM=type 2 diabetes mellitus FFA=free fatty acid PAI-1=plasminogen activator inhibitor-1 TNFα=tumor necrosis factor-alpha; Bray, G. J Clin Endocrinol Metab. 2004;89:2583-2589. IL-6=interleukin 6 ASCVD=atherosclerotic cardiovascular disease Eckel RH, et al. Lancet. 2005;365:1415-1428. C-C L2+chemokine (C-C motif) ligand2 Slide: Aronne LJ after Dr. G. Bray. ©2007 LPL=lipoprotein lipase

Obesity as a Disease

Mobility, GER, Osteoarthritis, Biomechanical Sleep Apnea, Incontinence

Obesity‐related Diabetes, CVD, Cardiometabolic Hypertension, comorbidities Dyslipidemia

Cancer (15+), Cancer/Other Psych Disorders, Androgen Deficiency

Pi‐Sunyer X. Postgrad Med. 2009;121:21‐33.

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Immunity to Obesity

• Patients and Providers fail to recognize obesity • 17‐55% patients with obesity are given that as a diagnosis • Many patients with obesity do not see themselves as having obesity

Kaplan LM et al. Obesity. 2018;26:1;61‐69. Ruser CB. J Gen Intern Med 2005. Dec;20(12):1139‐41.

AACE/ACE Obesity CPG, Endocr Pract. 2016;22(Suppl 3)

Stigma of Obesity

• Patients are frequently ashamed by their “failure” to successfully lose weight • Labeled as lazy, unmotivated1 • “Just eat less or move more” • Stigmatization limits weight loss success2 • Obesity • Reduces social, educational and financial opportunities • Limits social interactions, with individuals/partners and society • Reduces Self‐esteem

1. Wimalawansa SJ. J Clin Transl Endocrinol. 2014 Sept; 1(3): 73‐76. 2. Rebecca M. Puhl, et al. Annals of Behavioral Medicine, 51(5), 1 Oct 2017, 754–763

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Evidence‐Based Approach to Treating Obesity

• September 18, 2018Advise individuals with overweight and obesity who would benefit from weight loss to participate for ≥ 6 months in a – US Preventive Task Force Recommendation Statementcomprehensive lifestyle program that assists participants in adhering to a lower calorie diet and increasing physical activity through the use of behavioral strategies. (A‐Strong)

Challenges in Managing Obesity • Despite evidence supporting intensive behavioral interventions, most insurance providers do not cover obesity management / counseling • Only 5 FDA‐approved anti‐obesity medications • Orlistat (Xenical®, Alli®) • Phentermine/Topiramate (Qsymia®) • Locaserin (Belviq®) • Bupropion/naltrexone (Contrave®) • Liraglutide (Saxenda®) • Coverage limited • Requires Patient Activation • Time • Access to food • Family / community / workplace support

Challenges in Obesity Management

• 2018 weight loss market preObesity management per current treatment dicted to be >$70 billion1 guidelines in a single metropolitan area • Majority of dollars spent on commercial weight loss chains and meal replacements • Some estimate >$300 billion dollars per year when taking into account surgical weight loss procedures and associated costs

https://www.webwire.com/ViewPressRel.asp?aId=217481 Bloom B. Obesity (Silver Spring). Guideline‐concordant weight‐loss programs in an urban area are uncommon and difficult to identify through the internet. 2016 Mar; 24(3): 583–588.

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Challenges in Managing Obesity • Despite evidence supporting intensive behavioral interventions, most insurance providers do not cover obesity management / counseling • Only 5 FDA‐approved anti‐obesity medications • Xenical®, Qsymia®, Belviq®, Contrave®, Saxenda® • Coverage is limited • Requires Patient Activation • Time • Access to food • Family / community / workplace support • Unrealistic goals – Patients and Providers

Benefits of 5‐10% Weight Loss • Prevent T2DM1 • Increases life expectancy2 • Improves glycemic control3 • Lowers blood pressure4 • Improves serum lipid profile5 • Decrease cancer risk6 • Improves lower back pain, reflux, lower extremity arthralgias, sleep apnea7 • Can decrease drugs for obesity‐related conditions7 • Reduced Urinary incontinence, improved sexual function, improved QOL8

1. Hamman RF, et al. Diabetes Care. 2006;29(9):2102‐2107. 5. Dattilo et al. Am J Clin Nutr. 1992;56:320‐328. 2. Lean et al. Diabet Med. 1989;7:228‐233. 6. Bianchini F et al. Obesity Reviews 2002;3:5‐8 3. Wing et al. Arch Intern Med. 1987;147:1749‐1753. 7. NHLBI Guidelines, June 1998. 4. Schotte et al. Arch Intern Med. 1990;150:1701‐1704. 8. Look AHEAD. www.lookaheadtrial.org/public/bibliography.pdf

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Regulation of Hunger / Eating • Conscious and Subconscious Signaling • High prevalence of non‐normative and disordered eating associated with obesity • Emotional eating / non‐nutritional food consumption • Uncontrolled eating • Disordered eating • Binge Eating Disorder (BED) • Night Eating Syndrome (NES)

Berthoud HR. Proc Nutr Soc. 2012 Nov; 71(4): 478‐487.

Identify Weight Loss Hurdles

• Underlying Medical Conditions associated with weight gain / inability to lose weight • Medications • Sleep Disorders • Stressors – emotional, financial

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Medications Associated with Weight Gain Category Drugs That May Cause Weight Gain Possible Alternatives Antidiabetic agents Insulin, sulfonylureas, thiazolidinediones DPP‐4i, SGLT2i, GLP‐1 RAs, metformin β‐ and α‐blockers Propranolol, metoprolol, atenolol, doxazosin ACEIs, CCBs Steroid hormones Contraceptives, progesterone, glucocorticoids IUDs, Barrier methods, NSAIDs SSRIs (ADs) Paroxetine Fluoxetine, sertraline Tricyclics (ADs) Amitriptyline, nortriptyline, imipramine, doxepin Protriptyline, bupropion, nefazodone MAOIs (ADs) Phenelzine Other (ADs) Mirtazapine, duloxetine Bupropion Antihistamines Cyproheptadine Inhalers, decongestants Anticonvulsants Valproate, carbamazepine, gabapentin, pregabalin, Topiramate, lamotrigine, zonisamide, vigabatrin felbamate

Neuroleptics Thioridazine, haloperidol, olanzapine, quetiapine, Ziprasidone, aripiprazole risperidone, clozapine

Apovian CM. Pharmacologic Management of obesity: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2015;100(2):342–362.

Pharmacotherapy for Obesity

Drug Mechanism of Action Mean Weight Lossa Study Duration Phentermine Norepinephrine-releasing agent 3.6 kg 2 to 24 weeks

Pancreatic and gastric lipase inhibitor Orlistat 2.9- 3.4 kg 1 year

Lorcaserin 5HT2C receptor agonist 3.6 kg 1 year

1 year Phentermine/ GABA receptor modulation (topiramate) plus 6.6 – 8.6 kg topiramate norepinephrine-releasing agent (phentermine)

Reuptake inhibitor of dopamine and Naltrexone bupropion norepinephrine (bupropion) and opioid 4.8% 1 year antagonist (naltrexone)

Liraglutide GLP-1 agonist 5.8 kg 1 year

a. Mean weight loss in excess of placebo as percentage of initial body weight or mean kg weight loss over placebo. GABA: gamma-aminobutyric acid; GLP-1: glucagon-like peptide-1. Apovian C. J Clin Endocrinol Metab. 2015 2015 Feb;100(2):342-62.

Anti‐Obesity Medications

Srivastava G. Nature Reviews Endocrinology. Oct 2017 Mendieta-Zeron, H. Gen and Comp Endocrin. 155 (2008); 481-495.

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Low adoption of weight loss medications: A comparison of prescribing patterns of anti‐obesity pharmacotherapies and SGLT2s

Thomas CE. Obesity. 2016 September; 24(9):1955‐1961.

FDA Approval Criteria: Anti‐obesity Drug

• Standard guidelines were issued in the mid‐1990s • A new drug must induce statistically significant placebo‐ adjusted weight loss of: • >5% at 1 year or • >35% of patients should achieve >5% weight loss (which must be at least twice that induced by placebo) • In addition, the medication is required to show evidence of improvement in metabolic biomarkers, including blood pressure, lipid levels and glycemic control

www.fda.gov/downloads/Drugs/Guidances/ucm071612.pdf

Choosing an Anti‐Obesity Medication • Medications are indicated for • BMI >30 or >27 + comorbidity • Patients who have tried / failed at losing weight without medications • Improving adherence to diet and physical activity • Do no harm: know about interactions and contraindications • Consider secondary benefits of medications • Use shared decision making in choosing a medicine • Evaluate efficacy at ~3 months • Continue for long‐term use, like other chronic disease treatments

Apovian CM, Aronne LJ, Bessesen DH et al. Pharmacologic Management of obesity: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2015;100(2):342–362.

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Medications Require Behavioral Change

• All clinical trials included a “lifestyle intervention” • Diet Changes • Journaling – MyFitnessPal, LoseIT, Weight Watchers, etc. • Use of Meal Replacement products • Increased Activity • Incidental Activity • Structured Activity

Weight Maintenance EXERCISE DIET

Weight Loss Weight Maintenance

Unick JL. Clin Trials and Invest, Volume: 25(11): 1903‐1909. 20 September 2017

Physical Activity Recommendations

• On average, only 36% meet physical activity recommendations that “every U.S. adult accumulate 30 minutes or more of moderate physical activity 5 days per week or 20 minutes of vigorous physical activity 3 days per week”

www.nccd.cdc.gov

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Physical Activity – Participation in No Leisure‐time Activity

www.nccd.cdc.gov

Self‐Reported Obesity Among U.S. Adults

http://www.cdc.gov/obesity/data/prevalence‐maps.html

Fat Mass vs. Fat Free Mass

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Surgical and Endoscopic Treatments for Obesity

• Bariatric Surgery • Laparoscopic Sleeve Gastrectomy • Roux en Y Gastric Bypass • Others • Endoscopic Procedures • Intragastric Balloons • AspireAssist®

Weight Loss Surgery Options

Schauer P, Hanipah ZN, Rubino F. Cleve Clin J Med. 2017 Jul;84( Suppl 1):S47-S47- 56

Bariatric Surgery Criteria

BMI: <18.5 18.5-24.9 25.0-29.9 30.0-34.9 >35 >40 Underweight Normal Overweight Obesity I Obesity II Obesity III

With ≥1 With no Severe comorbidities Obesity‐ associated comorbidity

Mechanick JI, et al. Endocr Pract. 2013 Mar-Apr; 19(2): 337–372. 2013 Clinical Practice Guidelines for the Bariatric Patient

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Intragastric Balloons

AspireAssist

UAB Weight Loss Medicine Multidisciplinary clinic • Physicians / Nurse Practitioner: • Amy Warriner, MD, Director, Obesity Medicine Board Certified • Monica Agarwal, MD, Obesity Medicine Board Certified • Laura Rogers, MD, Obesity Medicine Board Certified • Meagan Gray, MD, Hepatologist • Mary Hanaway, NP • Amanda Edwards, NP • Dietitians / Diabetes Educators • Karin Crowell, RD, LD, MS, CDE • Karen MacPherson Harrison, RD, LD, MS, CDE • Leigh Ann Pritchett, RD, LD, MS • Erica Chen, RD, LD, MS, DMD • Behavioral Therapy • Ashley Hanson Gabriel, PhD

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UAB Weight Loss Medicine • Initial Visit: Bio‐Impedence, RMR, MD/NP, Dietitian • Clinic Membership Options • General • Bariatric • Maintenance • PREPARE Program • 3‐month partial meal‐replacement • Created for pre‐surgical weight loss requirements, i.e. ventral hernia, orthopedic • Other • Medicare Lifestyle Program • Shared Medical Visits for Pre‐Bariatric Insurance Mandated Visits • Diabetes Prevention Program

Resting Metabolic Rate Testing and Bioimpedence Analysis

Thank You