Intensification of Treatment: Pharmacotherapy for Obesity

9/17/20

Angela Golden, DNP, FNP-C, FAANP SCOPE certified OMA Advanced Certificate of Education in Obesity Medicine Owner and Provider at NP Obesity Treatment Center

Disclosures

• Related to Obesity – Novo Nordisk: Speakers bureau and Consultant – Unjury, Consultant • Other – Takeda/Lundbeck: Speakers bureau – Sanofi: Diabetes

Objectives

• Evaluate evidence-based guidelines for pharmacologic management of chronic disease of obesity • Identify available pharmacotherapeutics that can be utilized to support treatment of chronic disease of obesity

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Pharmacologic Therapy

Therapy Options, Factors to Consider When Selecting Therapy, and Efficacy/Safety Evidence

Therapeutic Goals

Reduce obesity- Weight loss of Improve patient associated 5%-10% of body complications health and weight quality of life within 6 months

Reduces CVD risk Reduces sleep factors apnea, depression Prevents/delays T2DM Improves physical Improves osteoarthritis function

Jensen MD, et al. Circulation 2014;129:S102-S138; Garvey WT, et al. Endocr Pract 2016;22 Suppl 3:1-203.; Yanovski SZ, et al. JAMA 2014;311:74-86; Apovian CM, et al. J Clin Endocrinol Metab 2015;100:342-62

FDA-Approved Short-Term (Anti) Obesity Therapies

Generic Drug* Dose Contraindications Side Effects

Phentermine 8mg-37.5mg Anxiety disorder, Insomnia, palpitations, CVD, hypertension, tachycardia, dry mouth, Diethylpropion 25 mg or 75 MAO inhibitors, taste alterations, mg, SR glaucoma, dizziness, tremors, Phendimetrazine 17.5-70 mg or hyperthyroidism, headache, diarrhea, 105 mg, SR seizures, pregnancy/ constipation, vomiting, Benzphetamine 25-50 mg breastfeeding, drug gastrointestinal distress, abuse history anxiety, restlessness, increased blood pressure

https://dailymed.nlm.nih.gov/dailymed/index.cfm; Bray GA, et al. Circulation 2012;125:1695-703 *Mechanism of action = Sympathomimetic— Apovian CM, et al. J Clin Endocrinol Metab 2015;100:342-62 noradrenergic causing appetite suppression

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Phentermine

• US Drug Enforcement Agency scheduled IV drug – Risk for addiction • Not indicated for long term use – 13 weeks by label

Endocrine Society allows for possible long-term use: § No CVD § No psychiatric/substance abuse history § Has been informed about therapies that are approved for long-term use § Document off-label use in patient’s medical record § No clinical significant increase in pulse/BP when taking phentermine § Demonstrates significant weight loss with phentermine § Start at 7.5 or 15 mg/d—dose escalate if not achieving significant weight loss § Monitor monthly during dose escalation

Apovian CM, et al. J Clin Endocrinol Metab 2015;100:342-62 7

Phentermine Study of Interest

• PC-II – 269 participants – 37.5 mg phentermine use longer than 2 years with abrupt withdrawal – Conclusions: • Phentermine abuse or psychological dependence (addiction) does not occur in patients treated with phentermine for obesity. • Amphetamine-like withdrawal does not occur upon abrupt treatment cessation even at doses much higher than commonly recommended and after treatment durations of up to 21 years Hendricks EJ, Greenway FL. A study of abrupt phentermine cessation in patients in a weight management program. Am J Ther. 2011;18(4):292-299. doi:10.1097/MJT.0b013e3181d070d7

FDA-Approved (Anti) Obesity Therapies

Generic listed Mechanism of Action alphabetically liraglutide (subcutaneous GLP-1 receptor agonist injection) naltrexone/bupropion ER Opioid receptor antagonist; dopamine and (oral) noradrenaline reuptake inhibitor orlistat (oral) Pancreatic lipase inhibitor—impairs gastrointestinal energy absorption, causing excretion of approximately 30% of ingested triglycerides in stool phentermine/ topiramate-ER Noradrenergic + GABA-receptor (oral) activator, kainite/AMPA glutamate receptor inhibitor causing appetite suppression

https://dailymed.nlm.nih.gov/dailymed/index.cfm

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Long-Term Efficacy for (Anti) Obesity Medications

Therapy (alphabetically) Length of Trial Mean Weight Loss liraglutide ≥1 year -7.4% (full dose) naltrexone/ ≥1 year -5.4% bupropion orlistat ≥1 year -6.1% phentermine/ ≥1 year - 9.8% (full dose) topiramate

; Bray GA, et al. Lancet 2016;387:1947-56

General Considerations in Pharmacologic Initiation

Pharmacologic interventions may be helpful as adjuvant therapy with lifestyle interventions for patients with BMI ≥30 kg/m2 or ≥27 kg/m2 with comorbidities.

• Different patients respond to different medications - If one option does not work, consider others § Discontinue medication in patients who do not respond with weight loss of at least 5% at 12 weeks after maximum dose* § Avoid in pregnancy - Pregnancy tests at baseline - Consider a disclosure signature *by label Liraglutide requires only 4% weight loss at 12 weeks after maximum dose

Apovian CM, et al. J Clin Endocrinol Metab 2015;100:342-62. 11

Orlistat

Dose Efficacy Contraindications/ Side Effects Frequency Precautions/ Warnings

60 mg OTC § Mean weight loss Chronic Oily spotting, ranged from 3.9%- malabsorption cramps, flatus 120 mg TID 10.2% at year 1 in 17 syndrome, with discharge, within 1 h of RCTs (120mg TID) pregnancy, fecal urgency, fat-containing § ↓ BP, TC, LDL-C, breastfeeding, fatty oily stool, meal fasting glucose at 1 cholestasis, some increased year medications (ex. defecation, fecal § Slows risk of warfarin, Incontinence Practical Considerationsprogression to T2DM antiepileptic agents, § Consider fat-soluble multivitamin levothyroxine, § Limit fat intake to 30% of calories cyclosporine) § Counsel on risk of GI adverse events

Lexicomp Bragg R, et al. J Am Assoc Nurse Pract 2016;28:107-15; Kahan S. Am J Manag Care. 2016;22:S186-S196 12

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Orlistat – Study of Interest

XENDOS • Randomized study for prevention of DM2 in patients w obesity (2004) • 4-year study of 3,305 patients with BMI >30 and normal or impaired glucose tolerance • Conclusion: “Compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinically representative obese population. Difference in diabetes incidence was detectable only in the IGT subgroup; weight loss was similar in subjects with IGT or NGT.” • DM 9% in placebo and 6.2% with orlistat – risk reduction of 37.3% Torgerson, J. (2004) XENDOS study, Diabetes Care, 27(1), 155-161. 13

Phentermine/Topiramate ER Dose Frequency Efficacy Contraindications/P Side Effects recautions/ Warnings § Initiate treatment § 10% weight loss Pregnancy and Paresthesias at 3.75 mg/23 with treatment vs breastfeeding, dizziness, taste mg for 2 weeks 2% placebo hyperthyroidism, alterations, § Increase to 7.5 § Improved glaucoma, use of insomnia, mg/46 mg cardiometabolic monoamine oxidase constipation, § Escalate to markers inhibitors dry mouth, elevation in 11.25mg/69mg § Reduced heart rate, memory or for 2 weeks then progression to cognitive changes to max 15 mg/92 T2DM mg Practical Considerations § Titrate dose at initiation and discontinuation § Drug Enforcement Agency Schedule IV drug § Risk Evaluation and Mitigation Strategy § Counsel about risk for mood disorders, suicidal thoughts § Taper highest dose every other day for 1 week if discontinuation is necessary § Women of childbearing age – pregnancy prevention plan and monthly pregnancy testing Lexicomp Bragg R, et al. J Am Assoc Nurse Pract 2016;28:107-15; Kahan S. Am J Manag Care. 2016;22:S186-S196 14

Phentermine/Topiramate ER Study of Interest

• Qsymia as an Adjunct to Surgical Therapy in the Superobese – Study done at Wake Forest University Health Sciences – ClinicalTrials.gov Identifier: NCT02301416 • This study tests the efficacy of the medication, Qsymia, as an adjunct therapy in superobese individuals planning to undergo weight loss surgery. • There was a significant increase in the odds of achieving BMI less than 40 for the experimental group compared with controls at 6 months

source: https://clinicaltrials.gov/ct2/show/NCT02301416 15

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Liraglutide

Dose Efficacy Contraindications/ Side Effects Frequency Precautions/ Warnings § Weekly § Mean weight loss Medullary thyroid Nausea, vomiting, titration by 9% at 1 year cancer history, diarrhea, 0.6mg over § Reduced multiple endocrine constipation, 5 weeks to progression to neoplasia type 2 hypoglycemia in target dose T2DM in patients history, history of patients with T2DM, of 3.0mg with prediabetes pancreatitis, increased lipase, § Reduced risk of pregnancy, increased heart rate, weight regain at 1 breastfeeding pancreatitis year Practical Considerations § Injectable administration § FDA approved for use in adults with BMI > 30kg/m2 or BMI > 27 kg/m2 with at least one complication. § Risk Evaluation and Mitigation Strategy (medullary thyroid carcinoma, acute pancreatitis)

Lexicomp Bragg R, et al. J Am Assoc Nurse Pract 2016;28:107-15; Kahan S. Am J Manag Care. 2016;22:S186-S196 16

Liraglutide Study of Interest

• SCALE Obesity and Prediabetes trial (2017) • 2,254patients – 80% less likely to develop diabetes than placebo group – 60% reverted to normoglycemia – of those that did go on to DM2 – took 2-7 times longer

leRoux, C., Astrup, A., Fujioka, K., Greenway, F., Lau, D., Gaal, L,. Ortiz, R., Wilding, J,. Skioth, T., Manning, L., & Pi-Sunyer, X. (2014). 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial, The Lancet, 389(10077), 1399-1409.

Naltrexone/Bupropion ER

Dose Frequency Efficacy Contraindications/ Side Effects Precautions/ Warnings § Initiate § Weight loss of Uncontrolled Nausea, 8mg/90mg x 1 8.2% vs 1.4% hypertension, constipation, week (placebo) seizure disorder, headache, § Weekly § Improved anorexia or bulimia, dizziness, escalation to cardiometabolic drug or alcohol vomiting, target dose of parameters withdrawal, chronic insomnia, dry 32mg/360 mg § Fewer cravings opioid use, mouth (2 tablets BID) § Lowered HbA1c in monamine oxidase patients with T2DM inhibitors, caution Transient with renal/hepatic increase in blood impairment pressure Practical Considerations § Titrate dose on initiation § Monitor blood pressure § Monitor closely for depression

Lexicomp Bragg R, et al. J Am Assoc Nurse Pract 2016;28:107-15; Kahan S. Am J Manag Care. 2016;22:S186-S196 18

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Naltrexone/Bupropion ER Studies of Interest

• CORI and II – COR II 1,496 participants – COR 1 1742 participants • Active treatment in the COR-I and COR-II trials was associated with significant improvements in eating control. • LIGHT – Cardiovascular outcome study with 8900 participants – Crashed and burned • data was released through a patent and securities filing without knowledge from the study's clinical-trial leaders • interim analysis was agreed on by the FDA but was intended only to show the medication did not double the risk of cardiovascular events, due to the reports of increased blood pressure • DSMB performed an analysis of data that included 50% of the enrolled patients. When this analysis was performed, investigators found no reduction in cardiovascular events Greenway, F. et al. (2010). Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-1): a multicenter, randomized, double-blind, placebo-cotrolled, phase 3 trial. Lancet, 21(9741), 595-605) Apovian, C. et al COR-II Study Group (2013). A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring, Md.), 21(5), 935–943. doi:10.1002/oby.20309 Nissen SE, Wolski KE, Prcela L, et al. Effect of Naltrexone-Bupropion on Major Adverse Cardiovascular Events in Overweight and Obese Patients With Cardiovascular Risk Factors: A Randomized Clinical Trial. JAMA.2016;315(10):990–1004. doi:https://doi.org/10.1001/jama.2016.1558 19

Ineffective Response to Therapy

• < 4-5% weight loss at 12 weeks of maximum dose Decrease dose • Medications with of existing AOM escalating doses – could be 16 weeks or as appropriate longer • Unable to tolerate Switch to a maximum doses different AOM • < ? 3% weight loss but with improvement in ORCs

Bray GA, et al. Lancet 2016;387:1947-56. Apovian CM, et al. J Clin Endocrinol Metab 2015;100:342-62.

IN BETWEEN “pills and surgery” Approved 4/16/2019 – early prescribers 10/2020

• Hydrogel matrix – cellulose and citric acid • First of its kind • Gelesis 100 (Plenity) – Mechanism of Action: capsule releases non-aggregating particles that absorb water – Increase the volume and elasticity of stomach and small intestines – Dosing: one capsule taken before lunch and dinner – Amount of loss: 59% lost at least 5%, 27% lost at least 10% – Can be used with BMI >25 kg/m2 < 40kg/m2 – SE GI minimal in study – Caution: patients with severe reflux or ulcers – NO RESTRICTION on how long it can be used

Greenway, et al. (2018). A Randomized, Double-Blind, Placebo-Controlled Study of Gelesis100: A Novel Nonsystemic Oral Hydrogel for Weight Loss. https://www.ncbi.nlm.nih.gov/pubmed/30421844

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Lorcaserin

• February 13th FDA requested Eisai withdraw lorcaserin – FDA – small increase in cancer] – CAMILLA-TIMI study 12,000 patients CVOT not cancer risk study • No increase in CV risk • Reduction in risk of diabetes • NEJM – signaled no difference in cancer risk • 3 years of data – lorcaserin 3.59% cancer, 3.50% placebo • FDA reported 7.7% in lorcaserin and 7.1% in placebo – No hearing, no publication https://conscienhealth.org/2020/02/fda-requests-lorcaserin-withdrawal-scant-disclosure/ https://www.fda.gov/drugs/drug-safety-and-availability/fda-requests-withdrawal-weight-loss-drug-belviq-belviq-xr-lorcaserin-market https://www.prnewswire.com/news-releases/eisai-to-voluntarily-withdraw-belviqbelviq-xr-in-the-us-301004885.html Bohula, E. et al. (2018). Cardiovascular Safety of Lorcaserin in Overweight or Obese Patients. N Engl J Med, 379, 1107-1117..

5 Step Strategy for Therapy Selection

Safety

Complications/Co- morbidities © Obesity Action Coalition

Patient history

Cost + insurance

Side effects

Example 5 step process

Safety Patient has no allergies to medication Complications HTN and insulin resistance, HTN and and/or depression are controlled Comorbidities Patient history No history of pancreatitis, seizures or FH of thyroid cancer Has tried OTC orlistat and couldn’t tolerate the SE Craving of sweets in the evening Cost & Insurance Patient has good insurance, but will require prior authorization Side Effects Has depression so will need monitored closely for all but orlistat, states cannot be fatigued

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Your Choice

Which medication would you recommend to the patient? a. liraglutide b. orlistat c. Phentermine d. naltrexone/bupropion ER e. phentermine/topiramate ER

Shared Decision Making liraglutide No contraindications – benefit on insulin (subcutaneous resistance. No history of pancreatitis or injection) FH of thyroid cancer naltrexone/bupropion No history of seizures ER (oral) Craving of sweets in the evening

0rlistat (oral) Patient tried this OTC and was unable to tolerate the GI side effects phentermine No contraindications – but will need to consider dosing at lower for long term phentermine/ No contraindications – BP will need topiramate-ER (oral) closely monitored. Patient has concern with fatigue and topiramate can have this

Maintaining Weight Loss

Weight regain typically occurs when medication is stopped1

Successful weight maintenance includes:2 • Self-monitoring • Weight loss of >2kg in 4 weeks • Frequent/regular attendance at weight loss program • Self-belief that weight can be controlled Maintaining weight loss is made difficult by the reduction in energy expenditure that weight loss induces

Continue the medical treatment program

1. Apovian CM, et al. J Clin Endocrinol Metab 2015;100:342-62.2. Thomas JG, et al. Am J Prev Med. 2014;46(1):17-23 27

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Physiology of Weight Regain

Adaptive responses to weight loss promotes weight regain.

§ Fall in energy expenditure

§ Increase in appetite

§ Dysfunctional hormonal

system Reprinted by permission, Copyright Clearance Center, Inc. Apovian CM, et al. J Clin Endocrinol Metab 2015;100:342-62 Apovian CM, et al. J Clin Endocrinol Metab 2015;100:342-62 Sumithran P, et al. New Engl J Med. 2011;365:1597-1604.

Key Take Aways

Obesity is a chronic and often progressive condition Obesity management is not about simply reducing numbers on the scale Intensify treatment with pharmacology

Evaluate medication success at “12 weeks”

If one medication doesn’t work, try another

With success, continue medical management

CONTACT INFORMATION

Angela Golden POB 25959 Munds Park, AZ 886017 (m) 928-814-8011 (f) 888-877-4669 [email protected] twitter: @DrAngieNP IG: npobesitytreatment www.npobesitytreatment.org

For an additional Obesity Resource: https://BookHip.com/RCPMFK

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© Angela K. Golden| Do not reproduce, cite or use for any purposes without explicit permission from the author any part of this presentation in any form. Requests for permission to make copies or use any part of the presentation please contact at [email protected]

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• The presentation information has been thoroughly researched and is evaluated for accuracy. Clinical practice is a constantly changing process and new information becomes available every day each provider is responsible to consult additional resources and apply information to their clinical practice as appropriate in addition to this presentation. • NP from Home, LLC disclaims any liability, loss, injury or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents of this presentation.

References/additional reading

• 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. • Armstrong, M. J., Mottershead, T. A., Ronksley, P. E., Sigal, R. J., Campbell, T. S. and Hemmelgarn, B. R. (2011), Motivational interviewing to improve weight loss in overweight and/or obese patients: a systematic review and meta-analysis of randomized controlled trials. Obesity Reviews, 12: 709–723. doi: 10.1111/j.1467-789X.2011.00892.x • Bales, C. W., Hawk, V. H., Granville, E. O., Rose, S. B., Shields, T., Bateman, L., Willis, L., Piner, L., Slentz, C., Houmard, J., Gallup, D., Samsa, G., & Kraus, W. E. (2012). Aerobic and Resistance Training Effects on Energy Intake: The STRRIDE AT/RT Study: Exercise Training Effects on Energy Intake. Medicine and Science in Sports and Exercise, 44(10), 2033–2039. http://doi.org/10.1249/MSS.0b013e318259479a • Byrne, S. & Barry, D. (2012). Predictors of weight loss success. Exercise vs. dietary self-efficacy and treatment attendance. Appetite, 58, 695-698.

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References/additional reading

• Bays HE, McCarthy W, Christensen S, Tondt J, Karjoo S, Davisson L, Ng J, Golden A, Burridge K, Conroy R, Wells S, Umashanker D, Afreen S, DeJesus R, Salter D, Shah N, Richardson L. Obesity Algorithm eBook, presented by the Obesity Medicine Association. www.obesityalgorithm.org. 2020. https://obesitymedicine.org/obesity-algorithm/ (February 22,2020). • Bragg R, Crannage E. Review of pharmacotherapy options for the management of obesity. J Am Assoc Nurse Pract. 2016;28(2):107-115. • Bray GA, Fruhbeck G, Ryan DH, Wilding JP. Management of obesity. Lancet. 2016;387(10031):1947-1956. • Bray GA, Ryan DH. Medical therapy for the patient with obesity. Circulation. 2012;125(13):1695-1703. • Chou W-yS, Prestin A, Kunath S. Obesity in social media: a mixed methods analysis. Translational Behavioral Medicine. 2014;4(3):314-323. • Clifton, P. (2017). Assessing the evidence for weight loss strategies in people with and without type 2 diabetes. World Journal of Diabetes, 8(10), 440–454. http://doi.org/10.4239/wjd.v8.i10.440 • Conlon, M. A.,&Bird, A. R. (2015). The Impact of Diet and Lifestyle on Gut Microbiota and Human Health. Nutrients, 7(1), 17–44. http://doi.org/10.3390/nu7010017

References/additional reading

• Daubenmier, J., Moran, P. J., Kristeller, J., Acree, M., Bacchetti, P., Kemeny, M. E., Dallman, M., Lustig, R., Grunfeld, C., Nixon, D., Milush, J., Goldman, V., Laraia, F., Laugero, K., Woodhouse, L., Epel, E., & Hecht, F. M. (2016). Effects of a mindfulness-based weight loss intervention in adults with obesity: A randomized clinical trial. Obesity (Silver Spring, Md.), 24(4), 794–804. http://doi.org/10.1002/oby.21396. • De Lorenzo, A., Soldati, L., Sarlo, F., Calvani, M., Di Lorenzo, N.,&Di Renzo, L. (2016). New obesity classification criteria as a toolfor bariatric surgery indication.World Journal of Gastroenterology,22(2), 681–703. http://doi.org/10.3748/wjg.v22.i2.681 • Dietrich MO, Horvath TL. Limitations in anti-obesity drug development: the critical role of hunger-promoting neurons. Nat Rev Drug Discov. 2012;11(9):675-691. • Dobkin BH. Wearable motion sensors to continuously measure real-world physical activities. Current Opinion in Neurology. 2013;26(6):602-608.

References/additional reading

• Flegal KM, Kruszon-Moran D, Carroll MD, et al. Trends in Obesity Among Adults in the United States, 2005 to 2014. JAMA. 2016;315(21):2284-2291. • Fruh, S. (2017). Obesity: Risk factors, complications, and strategies for sustainable long-term weight management. Journal of the American Association of Nurse Practitioners, 29(S1):S3-S14. • Gardner, C. D., Offringa, L. C., Hartle, J. C., Kapphahn, K. and Cherin, R. (2016), Weight loss on low-fat vs. low-carbohydrate diets by insulin resistance status among overweight adults and adults with obesity: A randomized pilot trial. Obesity, 24: 79–86. doi:10.1002/oby.21331 • Garvey WT, Mechanick JI, Brett EM, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity. Endocr Pract. 2016;22 Suppl 3:1-203. • Golden A. Obesity. In A. Hollier (Ed.), Clinical Guidelines in Primary Care. pp. 281-285, 2016. • Golden, A. (2017). Current pharmacotherapies for obesity: A practical perspective. Journal of the American Association of Nurse Practitioners, 29(S1):S43-S52.

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References/additional reading

• Goldstein, C. M., Thomas, J. G., Wing, R. R.,&Bond, D. S. (2017). Successful weight loss maintainers use health-tracking smartphone applications more than a nationally representative sample: comparison of the National Weight Control Registry to Pew Tracking for Health. Obesity Science&Practice, 3(2), 117–126. http://doi.org/10.1002/osp4.102 • Hall, K., Heymsfield, S., Kemnitz, J., Klein, S., Schoeller, D., & Speakmean, J. (2012). Consensus Statement: Energy balance and its components: Implications for body weight regulation. American Journal of Clinical Nutrition, 95, 989-94. • Harvey-Berino, J., West, D., Krukowski, R., Prewitt, E., VanBiervliet, A., Ashikaga, T., & Skelly, J. (2010). Internet Delivered Behavioral Obesity Treatment. Preventive Medicine, 51(2), 123–128. http://doi.org/10.1016/j.ypmed.2010.04.018 • Jakicic J, Davis KK, Rogers RJ et al. Effect of wearable technology combined with a lifestyle intervention on long-term weight loss: The IDEA randomized controlled trial. JAMA. 2016;316(11):1161-1171.

References/additional reading

• Jakicic, J. M. (2009), The Effect of Physical Activity on Body Weight. Obesity, 17: S34–S38. • Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guide-lines and The Obesity Society. J Am Coll Cardiol 2014;63:2985–3023.) • Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults. Circulation. 2014;129(25 suppl 2):S102-S138. • Kahan SK. Overweight and Obesity Management Strategies. Am J Manag Care 2016;22:S186-S196. • Klopfenstein, B. J., Kim, M. S., Krisky, C. M., Szumowski, J., Rooney, W. D., & Purnell, J. Q. (2012). Comparison of 3 T MRI and CT for the measurement of visceral and subcutaneous adipose tissue in humans. The British Journal of Radiology, 85(1018), e826–e830. http://doi.org/10.1259/bjr/57987644

References/additional reading

• Kushner, R. & Ryan, D. (2016). Screening and Diagnosis. The Journal of Family Practice, 65(70), S1-S4. • LeBlanc E, O’Connor E, Whitlock EP, et al. Effectiveness of primary care-relevant treatments for obesity in adults: A systemic evidence review for the US Preventive Services Task Force. Ann Intern Med. 2011;155(7):434 • leRoux, C., Astrup, A., Fujioka, K., Greenway, F., Lau, D., Gaal, L,. Ortiz, R., Wilding, J,. Skioth, T., Manning, L., & Pi-Sunyer, X. (2014). 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial, The Lancet, 389(10077), 1399-1409. • Leidy, H. J., Hoertel, H. A., Douglas, S. M., Higgins, K. A. and Shafer, R. S. (2015), A high- protein breakfast prevents body fat gain, through reductions in daily intake and hunger, in “Breakfast skipping” adolescents. Obesity, 23: 1761–1764. doi:10.1002/oby.21185 • Locke AE, Kahali B, Berndt SI, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518(7538):197-206. • Ma, C., Avenelli, A., Bollarnd, M., Hudson, J., Stewart, F., Robertson, C., Sharma, P., Fraser, Cl., & MacLennan, G. (2017). Effects of weight loss interventions for adults who are obese on mortality cardiovascular disease, and cancer: systematic review and meta- analysis. TheBMJ, 359:j4849 | doi: 10.1136/bmj.j4849 39

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References/additional reading

• McMacken, M.,&Shah, S. (2017). A plant-based diet for the prevention and treatment of type 2 diabetes. Journal of Geriatric Cardiology : JGC, 14(5), 342– 354. http://doi.org/10.11909/j.issn.1671-5411.2017.05.009 • Menni, C., Jackson, M., Pallister, T., Steves, C., Spector, T., & Valdes, A. (2017). Gut microbiome diversity and high-fibre intake are related to lower long-term weight gain. International Journal of Obesity, 41, 1099-1105. • Mozaffarian D. Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review. Circulation. 2016;133(2):187- 225. • Murray S, Tulloch A, Gold MS, Avena NM. Hormonal and neural mechanisms of food reward, eating behaviour and obesity. Nat Rev Endocrinol. 2014;10(9):540- 552. • Myles, I. A. (2014). Fast food fever: reviewing the impacts of the Western diet on immunity. Nutrition Journal, 13, 61. http://doi.org/10.1186/1475-2891-13-61 • Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA. 2014;311(8):806-814.

References/additional reading

• Perri, M., Limacher, M., Durning, P., Janicke, D., Lutes, L., Bobroff, L., Dale, M., Daniels, M., Radcliff, T., Martin, A. D. (2008). Treatment of Obesity in Underserved Rural Settings (TOURS): A Randomized Trial of Extended-Care Programs for Weight Management. Archives of Internal Medicine, 168(21), 2347–2354. http://doi.org/10.1001/archinte.168.21.2347.) • Piwek, L., Ellis, D. A., Andrews, S.,& Joinson, A. (2016). The Rise of Consumer Health Wearables: Promises and Barriers. PLoS Medicine, 13(2), e1001953. http://doi.org/10.1371/journal.pmed.1001953 • Reynolds, A.N., Mann, J.I., Williams, S. et al. Diabetologia (2016) 59: 2572. https://doi.org/10.1007/s00125-016-4085-2 • Ritten, A. & LaManna, J. (2017). Unmet needs in obesity management: From guidelines to clinic. Journal of the American Association of Nurse Practitioner, 29, S30-42. • Rogge, M., & Gautam. B. (2017). Biology of obesity and weight regain: Implications for clinical practice. Journal of the American Association of Nurse Practitioners, 29(S1):S15-S29.

References/additional reading

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