Comprehensive Overview of Obesity Management and Treatment Options

Obesity is a prevalent and severe health issue impacting both adults and children. This article delves into the prevalence of obesity, factors influencing it, and classification based on BMI. It also explores the impact of genetics, environment, behaviors, and other factors on weight gain. Additionally, it discusses various management options including medication therapy, lifestyle modifications, and bariatric surgery for individuals with different BMI levels.

• Obesity management
• Weight loss options
• BMI classification
• Medication therapy
• Bariatric surgery

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1. Obesity Management Lauren Bloch, PharmD Medication Therapy Management Pharmacist MHealth Weight Management Clinic

2. Review obesity prevalence, factors impacting obesity and obesity classification Learning Objectives Identify options for obesity management Discuss medication options currently available for weight loss

3. Obesity Prevalence Obesity is an epidemic and recognized as a disease CDC Prevalence of Obesity Among U.S. Adults, 2012 (above) 1 in 3 adults and 1 in 6 children are obese Severe obesity shortens lifespan by 10 years, similar to lifelong smoking CDC Prevalence of Obesity Among U.S. Adults, 2017 (above)

4. 1-3 What Factors Impact Obesity? GENETICS ECONOMICS DIET EXERCISE CO-MORBITIES MEDICATIONS ENVIRONMENT SLEEP SOCIETY BEHAVIORS HORMONES ???

5. Classifying Obesity BMI (kg/m Classification 2 ) < 18.5 Underweight 18.5-24.9 Normal 25-29.9 Overweight 30-34.9 Obesity (Class I) 35-39.9 Serious Obese (Class II) >40 Severe Obesity (Class III)

6. Genetics Condition related Event related What Caused Weight Gain? Drug-induced weight gain Poor eating behaviors Activity level Low socioeconomic status

7. Weight Management Options BMI 35 with co-morbidities BMI 40 without co-morbidities Bariatric Surgery Continuum of Care BMI 27 with co-morbidities BMI 30 without co-morbidities Pharmacotherapy Lifestyle Modifications BMI 25 (diet, physical activity, behavioral modifications) Reference 1

8. What is Bariatric Surgery Surgical procedure causing weight loss that alters the digestion process Types of procedures: Restriction: limiting the amount of food intake by reducing the stomach size Malabsorption: limiting the absorption of foods in the intestinal tract by bypassing a portion of the small intestine to varying degrees Combination of both restriction and malabsorption Hormonal Changes - Grehlin (hunger hormone) GLP1 and PYY (satiety hormones)

9. Types of Bariatric Surgery Lap Band Restrictive Sleeve Gastrectomy most common Restrictive, Hormonal Changes Roux-en-Y (Gastric Bypass) Restrictive, Malabsorptive, Hormone Changes Duodenal Switch (BPD-DS) Restrictive, Malabsorptive, Hormone Changes

10. Weight Management Options BMI 35 with co-morbidities BMI 40 without co-morbidities Bariatric Surgery Continuum of Care BMI 27 with co-morbidities BMI 30 without co-morbidities Pharmacotherapy Lifestyle Modifications BMI 25 (diet, physical activity, behavioral modifications) Reference 1

11. Which Weight Loss Medication is the Right One? Current eating behaviors Medical conditions Potential medication side effects Factors to Consider Insurance and cost Patient preference

12. Month 0 : Start weight loss medication (WLM) Assess safety and efficacy monthly for first 3 months Weight Loss If safety/tolerability concerns consider alter or discontinue +/- new option(s) Medication Timeline Assess for Effectiveness at Month 3 Ineffective (weight loss <5% body weight) OR safety/tolerability concerns discontinue, alter or try alternative option Effective (weight loss 5% body weight) continue Assess safety and efficacy every 3 months thereafter Reference 1

13. Weight Loss Medication Options FDA Approved for Weight Loss? Yes Yes No Yes No Liraglutide (Saxenda) - Yes Others - No Medications Phentermine/Topiramate (Qsymia) Phentermine Topiramate Naltrexone/Bupropion (Contrave) Naltrexone GLP-1 Agonists (e.g. Liraglutide, Semaglutide) Lorcaserin (Belviq) Orlistat (Xenical or Alli) Metformin Yes Yes No

14. Overview: Mechanisms of Action Reference 1 The Journal of Clinical Endocrinology & Metabolism, Volume 100, Issue 2, 1 February 2015, Pages 342 362, https://doi.org/10.1210/jc.2014-3415

15. MECHANISM: Stimulant sympathomimetic amine - reduces appetite CLINICAL PEARLS: Onset 1-2 weeks Can continue > 3 months if effective Eating behavior target: large portions or grazers DOSING: daily in AM Titrate dose slowly Tablet: 8 mg, 37.5 mg Capsule: 15 mg, 30 mg, 37.5 mg Phentermine Adipex-P , Lomaira Schedule IV DO NOT USE IN: Uncontrolled HTN or anxiety, arrhythmias, pulmonary HTN, glaucoma, hyperthyroidism, or CVD MONITORING: Blood pressure (BP), heart rate (HR), EKG? COMMON SIDE EFFECTS: constipation, dry mouth, headache, insomnia, jittery, anxiety, palpitations CAUTION 65 years old Reference 1-3

16. CLINICAL PEARLS: Takes weeks to feel effects Taste perversion: carbonated beverage use and alter taste of foods Two birds-one stone: migraines, insomnia, pain Time of dosing can be key MECHANISM: unclear, GABA enhancement? Increases satiety, reduces cravings, can alter taste of foods/drinks DOSING: Initiate nighttime dosing, then BID if necessary Titrate slowly Topiramate Topamax *Off label use DO NOT USE IN: History of kidney stones, glaucoma, cognitive impairment Risk of birth defects: women of child-bearing age, use contraception COMMON SIDE EFFECTS: drowsiness, paresthesia, dizziness, word finding issues, brain fog, taste perversion MONITORING: BMP, CBC, serum bicarb?, mental status, pregnancy test?; PHQ2/9? LESS COMMON: kidney stones, metabolic acidosis, cognitive impairment, rash Mild carbonic anhydrase inhibitor K+ & bicarb, chloride CAUTION: elderly, CKD, uncontrolled depression No target level Reference 1, 4-5

17. DOSING: once daily Initiate: 3.75mg-23 mg to 7.5 mg-46 mg Daily dose escalate at 3 months if needed Max: 15 mg-92 mg CLINICAL PEARLS: Dose dependent effectiveness synergistic relationship may decrease risk of side effects compared to singular entities split if not covered MECHANISM: Phentermine: reduces appetite Topiramate: reduces cravings, increases satiety, alter taste of foods/drinks Phentermine/ Topiramate Qsymia Schedule IV DO NOT USE IN: phentermine/topiramate slides MONITORING: phentermine/topiramate slides SIDE EFFECTS: phentermine/topiramate slides Reference 1, 6-7

18. MECHANISM: CLINICAL PEARLS: Dose around time of largest cravings/thinking about food/frequent snacking Will have to stop 4-5 days before surgery/procedure DOSING: Initiate: 1/2 (1/4?) tablet daily Titrate: to 1 tablet once or twice daily Tablet: 50 mg Opioid receptor antagonist Blocks POMC feedback loop to ensure POMC stays activated Works in mesolimbic reward pathway to decrease cravings Naltrexone ReVia *Off label use SIDE EFFECTS: Nausea, headache, anxiety?, Insomnia? MONITORING: LFTs, GAD7 if history of anxiety? DO NOT USE: Opioids on board, severe hepatic injury, uncontrolled anxiety Reference 1, 8-10

19. DOSING: NALTREXONE MECHANISM: previous BUPROPION MECHANISM: NDRI Stimulates POMC reducing hunger Mesolimbic pathway to modulate reward pathway CLINICAL PEARLS: If not covered, split Take PM dose in early evening to decrease insomnia Don t require max dose to acquire efficacy Week 1: 1 tab daily AM, Week 2: 1 tab BID, Week 3: 2 tabs in AM, 1 tab PM, Week 4: 2 tabs BID Tablet, SR 12 hour: naltrexone 8 mg/bupropion 90 mg Naltrexone/ Bupropion Contrave DO NOT USE IN: Taking opioids, MAOI or CYP2B6 inducers, history seizures, active bulimia or anorexia, uncontrolled HTN or anxiety MONITORING: BP, HR, LFTs, mental status Moderate-severe renal impairment: 1 tab BID Hepatic impairment: 1 tab daily COMMON SIDE EFFECTS: Headache, insomnia, nausea, constipation, vomiting, dizziness, dry mouth, tremor CAUTION: use with drugs metabolized by CYP2D6 or dopaminergic drugs Reference 1, 10-12

20. Glucagon-Like Peptide-1 (GLP-1) Agonists Saxenda: FDA approved Weight Loss Others: FDA approved Type 2 Diabetes, used off label in Prediabetes Daily Weekly Saxenda (liraglutide) Week 1: 0.6 mg daily, Week 2: 1.2 mg daily, Week 3: 1.8 mg daily, Week 4: 2.4 mg daily, Week 5 and after: 3 mg daily Victoza (liraglutide) Initial: 0.6 mg daily for 1-2 weeks, then 1.2 mg daily thereafter Dose escalation: 1.8 mg daily Byetta (exenatide IR) Initial: 5 mg twice daily, within 60 min before meal Dose escalation: 10 mg twice daily Ozempic (semaglutide) Initial: 0.25 mg weekly for 4 weeks, then 0.5 mg weekly thereafter Dose escalation: 1 mg weekly Trulicity (dulaglutide) Initial: 0.75 mg weekly Dose escalation: 1.5 mg weekly Bydureon (exenatide ER) Dose: 2 mg weekly Reference 1, 13

21. MECHANISMS: CLINICAL PEARLS: Subcutaneous injection Weight loss: semaglutide, liraglutide > dulaglutide, exenatide ER Dose at meal/bedtime or extend titration : side effects Cardioprotective - Liraglutide Brain GLP1 in hypothalamus, promoting satiety Pancreas insulin secretion & cell proliferation Periphery gut motility, insulin sensitivity in adipose & skeletal muscle GLP-1 Agonists COMMON SIDE EFFECTS: nausea, diarrhea, constipation, headache dyspepsia CAUTION: gastroparesis, GERD Can hypoglycemic effects of hypoglycemia-associated agents DO NOT USE IN: Self or family history of medullary thyroid carcinoma or MEN2, history of pancreatitis Exenatide if GFR <30 mL/min MONITORING: BMP, A1c, blood sugars as necessary Liraglutide, semaglutide dulaglutide: no dose adjust in CKD stage 2 & 3 Reference 1, 13-14, 23

22. CLINICAL PEARLS: Weight loss effects not as significant as other options DOSING: IR: 10 MG BID ER: 20 mg once daily MECHANISM: Selective serotonin 2C (5- HT2C) receptor agonist promoting satiety and decreasing food intake Lorcaserin Belviq DO NOT USE IN: Multiple other medications impacting serotonin Valvulopathy MONITORING: Mental status, edema, dyspnea COMMON SIDE EFFECTS: Nausea, dizziness, headache, fatigue, constipation, diarrhea, dry mouth CAUTION: Use if already taking medication impacting serotonin Reference 1, 15, 16

23. DOSING: CLINICAL PEARLS: Inhibits dietary fat absorption 25-30% Minimal absorption Good for patient eating high fat diet MECHANISM: Lipase inhibitor in stomach and intestine, inhibits hydrolysis of triglycerides to absorbable fatty acids 60 mg or 120 mg: 3 times daily at or within 1 hour of fat- containing meal Xenical: 120 mg (RX) Alli: 60 mg (OTC) Orlistat Xenical , Alli DO NOT USE IN: Cholestasis or malabsorptive syndromes MONITORING: None COMMON SIDE EFFECTS: Abdominal pain, defecation urgency, anal discharge, oily flatulence, increased defecation, steatorrhea Reference 1, 17,18

24. MECHANISM: hepatic glucose absorption and intestinal absorption, improves insulin sensitivity CLINICAL PEARLS: Take with meals ER decreases side effects Antipsychotic-induced weight gain? DOSING: Once to twice daily, titrate slowly Tablet: 500 mg, 850 mg, 1000 mg ER tablet: 500 mg Metformin Glucophage *Off label use MONITORING: BMP (Cr, GFR), blood sugars, A1c B12 every 2-3 years, cobalamin deficiency risk COMMON SIDE EFFECTS: Diarrhea, nausea, gas, stomach upset DO NOT USE: GFR <30 mL/min GFR 30 to <45 mL/min: do not start, consider decrease 1000 mg daily Reference 1, 10-12

25. Listen to the patients story this is imperative to identify best treatment approach to combat weight gain No matter the treatment option - lifestyle changes and behavioral modifications are necessary for optimal results Weight loss medications require close monitoring to assess safety and efficacy Big Picture If one weight loss medication doesn't work, that does not mean that others will not either

26. Still have questions or comments? Contact Information: Lauren Bloch lturner5@fairview.org

27. References [1] Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol & Metab. 2015;100(2):342-362. doi: 10.1210/jc.2014-3415. [2] Phentermine Hydrocholoride Oral. Drug Facts and Comparisons. Facts & Comparisons eAnswers. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.factsandcomparisons.com. Accessed May 1 2019. [3] Phentermine Hydrochloride. Micromedex Solutions. Truven Health Analytics, Inc. Ann Arbor, MI. Available at: http://www.micromedexsolutions.com. Accessed May 1 2019. [4] Topiramate Oral. Drug Facts and Comparisons. Facts & Comparisons eAnswers. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.factsandcomparisons.com. Accessed May 1 2019. [5] Topiramate. Micromedex Solutions. Truven Health Analytics, Inc. Ann Arbor, MI. Available at: http://www.micromedexsolutions.com. Accessed May 1 2019. [6] Phentermine Hydrochloride/Topiramate Oral. Drug Facts and Comparisons. Facts & Comparisons eAnswers. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.factsandcomparisons.com. Accessed May 1 2019. [7] Phentermine/Topiramate. Micromedex Solutions. Truven Health Analytics, Inc. Ann Arbor, MI. Available at: http://www.micromedexsolutions.com. Accessed May 1 2019. [8] Naltrexone Hydrochloride Oral. Drug Facts and Comparisons. Facts & Comparisons eAnswers. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.factsandcomparisons.com. Accessed May 1 2019. [9] Naltrexone Hydrochloride. Micromedex Solutions. Truven Health Analytics, Inc. Ann Arbor, MI. Available at: http://www.micromedexsolutions.com. Accessed May 1 2019.

28. References [10] About Contrave Contrave (Naltrexone HCl/Bupropion HCl). Naltropion Pharmaceuticals, Inc. 1 Apr. 2019. https://contrave.com/how-contrave- works/. [11] Naltrexone Hydrochloride/Bupropion Hydrochloride Oral. Drug Facts and Comparisons. Facts & Comparisons eAnswers. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.factsandcomparisons.com. Accessed May 1 2019. [12] Naltrexone Hydrochloride/Bupropion Hydrochloride. Micromedex Solutions. Truven Health Analytics, Inc. Ann Arbor, MI. Available at: http://www.micromedexsolutions.com. Accessed May 1 2019. [13] Glucagonlike Peptide 1 Receptor Agonists. Drug Facts and Comparisons. Facts & Comparisons eAnswers. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.factsandcomparisons.com. Accessed May 2 2019. [14] MacDonald PE, El-kholy W, Riedel MJ, et al. The Multiple Actions of GLP-1 on the Process of Glucose-Stimulated Insulin Secretion. Diabetes 2002 Dec; 51(suppl 3): S434-S442. https://doi.org/10.2337/diabetes.51.2007.S434. [15] Lorcaserin Hydrochloride Oral. Drug Facts and Comparisons. Facts & Comparisons eAnswers. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.factsandcomparisons.com. Accessed May 2 2019. [16] Lorcaserin Hydrochloride. Micromedex Solutions. Truven Health Analytics, Inc. Ann Arbor, MI. Available at: http://www.micromedexsolutions.com. Accessed May 2 2019. [17] Orlistat Oral. Drug Facts and Comparisons. Facts & Comparisons eAnswers. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.factsandcomparisons.com. Accessed May 2 2019. [18] Oralistat. Micromedex Solutions. Truven Health Analytics, Inc. Ann Arbor, MI. Available at: http://www.micromedexsolutions.com. Accessed May 2 2019.

29. References [19] Wang M , Tong JH , Zhu G et al. Metformin for treatment of antipsychotic-induced weight gain: A randomized, placebo-controlled study . Schizophr Res 2012 ; 138 : 54 57. [20] Seifarth C, Schehler B, Schneider HJ. Effectiveness of Metformin on Weight Loss in Non-Diabetic Individuals with Obesity. Exp Clin Endocrinol Diabetes 2013; 121: 27 31. http://dx.doi.org/ 10.1055/s-0032-1327734. [21] Metformin Hydrochloride Oral. Drug Facts and Comparisons. Facts & Comparisons eAnswers. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.factsandcomparisons.com. Accessed May 2 2019. [22] Metformin Hydrochloride. Micromedex Solutions. Truven Health Analytics, Inc. Ann Arbor, MI. Available at: http://www.micromedexsolutions.com. Accessed May 2 2019. [23] Dar S, Tahrani AA, Piya MK. The role of GLP-1 receptor agonists as weight loss agents in patients with and without type 2 diabetes. Practical Diabetes Vol. 32 No. 8. 17 September 2015.