Best Practices in Obesity Management: The Role of New and Emerging Therapies

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1 Angela Golden DNP, FNP-C, FAANP Angela Golden Novo Nordisk: Speaker and Advisory Bureau Health-Script (Orexigen): Speaker s Bureau Identify key recommendations and strategies from current clinical guidelines for the management of obesity Compare the safety, efficacy, and pharmacokinetic profiles of anti-obesity medications Identify best practices for selecting, initiating, and advancing appropriate pharmacological therapies for patient-specific management of obesity 1

2 Adult Obesity: 2016 Obesity and its Consequences te o fo b e si ty. o rg/a d u l t-obesity/ Overweight or obesity affects 69% of adults 20 years 1 Obesity affects ~35% adults 20 years 1 Asian American Non-Hispanic White Lat ino African American 60 Percentage Significant increase in Stage 3 obesity for women Female Male GENDER AGE ETHNICITY 1. Ogden C et al. JAMA 2014;311: Flegal KM, et al. JAMA. 2016;315(21): Flegal KM, et al. JAMA. 2016;315(21): Heritable traits Chromosomal abnormalities Genetic Environmental Endocrine disrupting chemicals Low macronut rient /high calo rie fo o ds Go lde n A. Obesity. In A. Hollier (Ed.) 2016: Lo ck e A, e t a l. Nature. 2015; 518(7538): ? Medications causing weight gain Obesogenic Medications Physiologic Altered microbiome GI/CNS regulation of hunger + satiety hormones GI, gastro inte stinal; CNS, ce ntral ne rvo us syste m The Complexity of Appetite Regulation GLP-1 = glucagon-like peptide 1 CCK = cholecystokinin YY = peptide YY FFA = free fatty acids AA = amino acids Die trich MO, e t al. Nat Re v Drug Disc. 2012;11(9): Suzuki K, et al. Exp Diabetes Re s. 2012;2012:824 Mu rra y S, e t a l. Nat Rev Endocrinol ; 1 0: Reprinted by permission from Macmillan Publishers Ltd: Nat Re v Drug Disc. 2012;11(9): ; permission conveyed through Copyright Clearance Center, Inc. 2

3 Die trich MO, e t al. Nat Re v Drug Disc. 2012;11(9): Suzuki K, et al. Exp Diabetes Re s. 2012;2012:824 Mu rra y S, e t a l. Nat Rev Endocrinol ; 1 0: The Complexity of Appetite Regulation GABA = γ-aminobutyric acid, AgRP = agouti-related protein, NPY = neuropeptide, α-msh = alpha-melanocyte-stimulating hormone, POMC = pro-opiomelanocortin, CART = cocaine and amphetamine-regulated transcript, MC4 = melanocortin 4 receptor Reprinted by permission from Macmillan Publishers Ltd: Nat Re v Drug Disc. 2012;11(9): ; permission conveyed through Copyright Clearance Center, Inc. Adaptive responses to weigh loss promotes weight regain. Fall in energy expenditure Increase in appetite Dysfunctional hormonal system Physiology of Weight Regain Apovian CM, et al. J Clin En do crino l Me tab ; 1 00 : Sumithran P, et al. Ne w Eng l J Me d. 2011;365: Reprinted by permission, Copyright Clearance Center, Inc.Apovian CM, e t a l. J Clin En d ocrin ol Me ta b 2015;100: Body Mass Index (BMI) in kg/m 2 Overweight Class 1 Obesity Class 2 Obesity Class 3 Obesity w/comorbidities Men Abdominal Obesity Waist Circumference Women Abdominal Obesity >/ = 40 inches (>102 cm) >/ = 35 inches (>88cm) Garve y WT, e t al. Endocr Pract 2016;22 Suppl 3:1-20 Apovian CM, et al. J Clin Endocrinol Me ta b 2015;100: Waist circumference cut-points differ by ethnicity Endocrine Society Pre-obesity: 26 kg/m 2 Diabetes risk, metabolic syndrome, and Nonalcoholic fatty liver disease Polycystic ovary syndrome prediabetes The Type adverse 2 diabetes health consequences of increased body Dyslipidemia fat (especially visceral Female fat) infertility are not just comorbidities Hypertension or associated Male hypogonadism risk factors. Cardiovascular disease Obstructive sleep apnea and cardiovascular Asthma disease mortality Osteoarthritis Urinary stress Depression incontinence Garve y WT, e t al. Endocr Pract 2016;22 Suppl 3:1-203; Bays HE, Seger JC, Primack C, McCarthy W, Long J, Schmidt SL, Daniel S, Wendt J, Horn DB, We stma n EC: Obesity Algorithm, presented by the Obesity Medicine Association Obesity is a complex, multifactorial, chronic disease Obesity is defined as a chronic, relapsing, multifactorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissues dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences. Obesity is associated with a significant increase in mortality and many health risks The higher the BMI, the greater the risk of morbidity and mortality Bays HE, Seger JC, Primack C, McCarthy W, Long J, Schmidt SL, Daniel S, Wendt J, Horn DB, We stma n EC: Obesity Algorithm, presented by the Obesity Medicine Association Je n se n MD, e t a l. Circulation 2014;129:S102-S138 3

4 42 years old Works part-time as a banker Lives with her husband and 2 daughters Has tried multiple times to lose weight Tried phentermine in past for weight loss but did not tolerate the side effects ( felt jittery ) Has not reached her weight goal How would you approach evaluation? Obesity Action Coalition n te n t/u p l o a d s/ob e si tya cti o n _ P ortra i ts_ -375.jpg Ask Assess Permission to discuss weight BMI, waist circumference, obesity stage Explore readiness for change Explore drivers + complications of excess weight History: weight, activity, nutrition, family Laboratory studies Complete blood count (CBC), fasting lipid panel, fasting glucose, HbA1c, liver function tests, vitamin D, thyroid stimulating hormone (TSH) Advise Health risks of obesity + benefits of weight loss Expectations + Agree targets Long-term strategy + treatment options Behavioral changes Assess + treat obesity-related comorbidities Examples: sleep apnea, depression Physical exam Measure weight + height to calculate BMI Waist circumference for patients w/ BMI >25kg/m 2 Blood pressure Assist Identify barriers to optimal health Create follow -up plan VallisM, e t a l. Can Fam Physician : Je n se n MD, e t a l. Circulation 2014;129:S102-S138; Garvey WT, et al. Endocr Pract 2016;22 Suppl 3:1-203 Sleep Apnea: intermittent use of CPAP GERD: treated with protonix Osteoarthritis both knees: takes intermittent ibuprofen Reproductive barrier: IUD Mild depression and anxiety: treated successfully with citalopram ETOH: drinks socially 1 glass of wine/week. No illicit drugs. No history of seizures, hypertension, heart disease, or pancreatitis BMI 29 kg/m 2 CMP, CBC,TSH noncontributory TC= 245 LDL = 134 TG = 173 HgbA1C = 5.8 PHQ9 = 4 BMI, body mass index; CMP, comprehensive metabolic panel; CBC, complete blood count; TSH, thyroid stimulating hormone; TC, total ch o l e ste ro LDL, l o w-density lipoprotein; TG, triglycerides; HbA1c, glycated hemoglobin; PHQ9, Patient Health Questionnaire Obesity Action Coalition I ve been overweight since I was 17. I m always thinking about food, especially sweets and snacks. I find it hard to curb my cravings inste ad of eating only a few chips, I usually end up eating the whole bag. I ve tried to lose weight many, many times at least 6 or 7. Sometimes I do lose weight, but I always gain it back again. I m getting real frustrated. 4

5 Prediabetes Depression GERD Osteoarthritis Weight gain Regain Cravings Best Practice Strategies What would you recommend as next steps in management? Similarities 1-3 Individualized eating plans Counseling patients to increase physical activity Behavioral interventions Medication may be appropriate for some patients Referral to an obesity specialist or surgery may be appropriate New Focus Differences 1 Endocrine Society paradigm shift toward pharmacologic therapy over no therapy at all for patients: With a history of unsuccessful weight lost and maintenance Who meet label indications Weight loss of 5%-10% of body weight Reduce obesityassociated complications within 6 months Reduces CVD risk factors Prevents/delays T2DM Improves osteoarthritis Improve patient health and quality of life Reduces sleep apnea, depression Improves physical function 1. Apovian CM, et al. J Clin En d o crin o l Me ta b 2015;100: Garve y WT, e t al. Endocr Pract 2016;22 Suppl 3: Jensen MD, et al. Circulation 2014;129:S102-S138 Je n se n MD, e t a l. Circulation 2014;129:S102-S138; Garvey WT, e t a l. En d o cr Pract 2016;22 Suppl3: ; Yanovski SZ, et al. JAMA 2014;311:74-86;Apovian CM, e t a l. J Clin EndocrinolMe ta b ; : Meal Plan Physical Activity Behavior Energy deficit 500kcal/day Lo w-carb Lo w-fat Volumetric High protein Vegetarian Mediterranean DASH Individualized Increase leisure time physical Track progress: activity Daily activity logs Pedometer logs Decrease Training metrics sedentary time >150 mins/week on 3-5 separate days Self-monitoring Goal setting Education Problem-solving strategies Stimulus control Stress reduction Counseling Jensen MD, et al. Circulation 2014 ;129:S102 -S138. Garve y WT, e t al. Endocr Pract 2016;22 Su pp l 3: Mo za ffa ri a n D. Ci rcu la t i on Ja n ;1 3 3( 2 ) : *Alone or with adjunctive therapies 5

6 Applications to log nutrition and physical activity Explore readiness to change Think: Motivational Interviewing & Shared Decision Making Body-weight scales w/feedback Wearable technology Continue lifestyle therapy Websites Social media Agree on weight loss goal of 5-7% of Pamela s current weight Consensus to discuss medication options Do bk in BH. Curr Opin Ne uro l : Chou WY, et al. Tra n sl Behav Me d : Ja k icic J, e t a l. JAMA 2016;316: Obesity Action Coalition A. Orlistat (Alli, Xenica) B. Phentermine/topiramate (Qsymia) C. Naltrexone/bupropion (Contrave) D. Phentermine (Adipex) E. Liraglutide (Saxenda) F. Lorcaserin (Belviq, Belviq XR) Therapy Options, Factors to Consider When Selecting Therapy, and Efficacy/Safety Evidence Generic Drug* Dose Contraindications Side Effects Phentermine Diethylpropion 8mg-37.5mg 25 mg or 75 mg, SR Anxiety disorder,cvd, hypertension, MAO inhibitors, glaucoma, Insomnia, palpitations, tachycardia, dry mouth, taste alterations, dizziness, Phendimetrazine mg or 105 hyperthyroidism, seizures, tremors, headache, pregnancy/breastfeeding, diarrhea, constipation, mg, SR drug abuse history vomiting, gastrointestinal Benzphetamine mg distress, anxiety, restlessness, increased blood pressure US Drug Enforcement Agency scheduled 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 fo r lo ng-term use Document off-label use in patient s medical record No clinical significant increase in pulse/bp when tak ing 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 m; Bray GA, e t al. Circulation 2012;125: Apovian CM, et al. J Clin Endocrinol Me ta b 2015;100: *Mechanism of action = Sympathomimetic noradrenergic ca u si n g a p p e ti te su p p re ssi o n Apovian CM, et al. J Clin Endocrinol Me ta b 2015;100:

7 Generic Drug Orlistat (oral) Lorcaserin (oral) Phentermine/ topiramate- ER (oral) Liraglutide (subcutaneous injection) Naltrexone SR/bupropion Mechanism of Action Pancreatic lipase inhibitor impairs gastrointestinal energy absorption, causing excretion of approximately 30% of ingested triglycerides in stool Highly selective serotonergic 5-HT2C receptor agonist causing appetite suppression Noradrenergic + GABA-receptor activator, kainite/ampa glutamate receptor inhibitor causing appetite suppression GLP-1 receptor agonist Opioid receptor antagonist; dopamine and noradrenaline reuptake inhibitor Therapy Length of Trial Total Weight Loss Mean Weight Loss Orlistat 1 year -5.3 kg -6.1% Lorcaserin 1 year -5.8 kg -5.8% Phentermine/ topiramate Bupropion/ naltrexone 1 year kg - 9.8% 1 year -6.1 kg -5.4% Liraglutide* 1 year -8.4kg -8.0% m Le B l a n c E, e t a l. Ann Intern Med 2011;155:434; Vilsbøll T, e t a l. BMJ 2012;344:d7771 ; Bray GA, et al. Lancet 2016;387: *Pi-Sunyer X, et al. Ne w Engl J Me d 2015; 373: Safety Pharmacologic interventions may be helpful as adjuvant therapy with lifestyle interventions for patients with BMI 30 kg/m 2 or 27 kg/m 2 with comorbidities. Co-morbidities 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 Avoid in pregnancy - Pregnancy tests at baseline - Consider a disclosure signature Patient history Cost + insurance Side effects Obesity Action Coalition Apovian CM, et al. J Clin Endocrinol Me ta b 2015;100: Dose Frequency 60 mg OTC 120 mg TID within 1 h of fat-containing meal Efficacy Side Effects Contraindications Mean weight loss ranged from 3.9%- 10.2% at year 1 in 17 RCTs (120mg TID) BP, TC, LDL-C, fasting glucose at 1 year Slows risk of progression to T2DM Practical Considerations Consider fat-soluble multivitamin Limit fat intake to 30% of calories Counsel on risk of GI adverse events Le xi co mp Oily spotting, cramps, flatus with discharge, fecal urgency, fatty oily stool, increased defecation, fecal incontinence Bragg R, et al. J Am Assoc Nurse Pract 2016;28:107-15; Kahan S. Am J Ma n a g Care. 2016;22:S186-S196 Chronic malabsorption syndrome, pregnancy, breastfeeding, cholestasis, some medications (ex. warfarin, antiepileptic agents, levothyroxine, cyclosporine) Dose Frequency Efficacy Contraindications Side Effects Initiate treatment at 3.75 mg/23 mg fo r 2 we e k s Increase to 7.5 mg/46 mg Escalate to 11.25mg/69mg fo r 2 we e k s t he n to max 15 mg/92 mg Le xi co mp 10% weight loss with treatment vs 2% placebo Improved cardiomet abolic markers Reduced progression to T2DM Pregnancy and breastfeeding, hyperthyroidism, glauco ma, use of monoamine oxidase inhibitors Paresthesias dizziness, taste alterations, insomnia, const ipat ion, dry mouth, elevation in heart rate, memory or cognitive changes 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 Bragg R, et al. J Am Assoc Nurse Pract 2016;28:107-15; Kahan S. Am J Ma n a g Care. 2016;22:S186-S196 7

8 Le xi co mp Dose Frequency Efficacy Contraindications Side Effects Weekly titration by 0.6mg over 5 weeks to target dose of 3.0mg Mean weight loss 9% at 1 year Reduced progression to T2DM in patients with prediabetes Reduced risk of weight regain at 1 year Medullary thyroid cancer history, multiple endocrine neoplasia type 2 history, history of pancreatitis, pregnancy, breastfeeding Nausea, vomiting, diarrhea, constipation, hypoglycemia in patients with T2DM, increased lipase, increased heart rate, pancreatitis Practical Considerations Injectable administration FDA approved for use in adults with BMI > 30kg/m 2 or BMI > 27 kg/m 2 with at least one complication. Risk Evaluation and Mitigation Strategy (medullary thyroid carcinoma, acute pancreatitis) Bragg R, et al. J Am Assoc Nurse Pract 2016;28:107-15; Kahan S. Am J Ma n a g Care. 2016;22:S186-S196 Dose Frequency Efficacy Contraindications Side Effects 10 mg twice daily ER 20mg daily Le xi co mp Average weight loss 8%-10% Pregnancy, breastfeeding Improved cardiovascular risk fact o rs Improved HbA1c in patients with T2DM Reduced risk of developing T2Dm in patients with prediabetes Caution with serotoninergic agents (due t o risk o f serotonin syndrome) Avoid in patients w/severe hepatic or renal insufficiency, valvular heart disease Practical Considerations Schedule IV Drug ER is slowly absorbed and lasts throughout the day Independent effect on lowering HgbA1 c Bragg R, et al. J Am Assoc Nurse Pract 2016;28:107-15; Kahan S. Am J Ma n a g Care. 2016;22:S186-S196 Headache, dizziness, fat igue, nause a, dry mouth, cough, and const ipat ion Patients w/t2dm, back pain, cough, hypoglycemia Dose Frequency Efficacy Contraindications Side Effects Initiate 8mg/90mg x 1 week Weekly escalation to target dose of 32mg/360 mg (2 tablets BID) Le xi co mp Weight loss of 8.2% vs 1.4% (placebo) Improved cardiometabolic parameters Fewer cravings Lowered HbA1c in patients with T2DM Uncontrolled hypertension, seizure disorder, anorexia or bulimia, drug or alcohol withdrawal, chronic opioid use, monamine oxidase inhibitors Practical Considerations Titrate dose on initiation Monitor blood pressure Monitor closely for depression Bragg R, et al. J Am Assoc Nurse Pract 2016;28:107-15; Kahan S. Am J Ma n a g Care. 2016;22:S186-S196 Nausea, constipation, headache, dizziness, vomiting, insomnia, dry mouth Transient increase in blood pressure Begin therapy with naltrexone-bupropion Effective response to therapy Improvement in cardiovascular risk markers Initiate 8mg/90mg x 1 week Escalate to target dose of 32mg/360 mg Weekly follow up monitoring 5% of baseline body weight at 3 months 5%-10% overall reduction of risk for T2DM, HTN, CVD At week 16 (includes titration period) Pamela has lost 2% of her baseline weight and her HbA1c remains 5.8%. What would be your next management step? If no clinical improvement after 12 weeks with one anti-obesity medication, consider: Increasing anti-obesity medication dose, if applicable OR Alternative antiobesity medication Bray GA, et al. La n ce t ; : Apovian CM, et al. J Clin Endocrinol Me ta b 2015;100:

9 Weight regain typically occurs when medication is stopped 1 LORCASERIN? No history of CVD but borderline high LDL/TC Caution w/ssri Monitor for depression LIRAGLUTIDE? HbA1c remains elevated No family history of thyroid or pancreatitis 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 1. Apovian CM, et al. J Clin Endocrinol Me ta b 2015;100: Thomas JG, et al. Am J PrevMe d. 2014;46(1):17-23 Weight loss <5% at 3 months with approved medication Safety or tolerability issues Patient-centered concerns BMI 40 kg/m 2 if surgical risk is acceptable BMI 35 kg/m 2 if >1 obesity-related disease BMI kg/m 2 for T2DM and/or metabolic syndrome Inability to achieve + sustain healthy weight loss with prior weight loss efforts Apovian CM, et al. J Clin Endocrinol Me ta b 2015;100: Rubino F, et al. Diab Care 2016;39: Apovian CM, et al. J Clin Endocrinol Me ta b 2015;100: Je n se n MD, e t a l. Circulation 2014;129:S102-S138. Obesity Action Coalition She has visited 10 times in 6 months for intensive behavioral therapy and monitoring. ü Lost 8% baseline weight ü HbA1c = 5.4% ü Sleep apnea is minimal ü No longer requires ibuprofen for osteoarthritis ü Walking 10,000 steps/day, 5 days/week ü Hiking with friends on weekends ü Signed up for a charity 5K Provider F/U ü Close follow-up ü Continue to prescribe medication with lifestyle ü Pregnancy prevention plan ü Close follow-up 9

10 Obesity is a chronic and often progressive condition Obesity management is not about simply reducing numbers on the scale Early intervention means addressing root causes and removing roadblocks Success is different for every individual A patient s best weight may never be an ideal weight NO SHAME, NO BLAME Adapted from Diabetes Prevention Program 1 LOOK AHEAD 3 Multi-center trial in patients with impaired glucose tolerance Weight loss of 7% reduced the rate of progression from impaired glucose tolerance to diabetes by 5% Reduced risk factors for CVD over 15 years ethically diverse overweight/obese adults w/t2dm Year 1: 5% weight loss in 68% who received intensive lifestyle counseling vs 13.3% who received usual care Year 8: 5% weight loss in 50.5% who received intensive lifestyle counseling vs 35.7% who received usual care Self-monitoring e.g., food diaries Controlling or modifying the stimuli that activate eating Slowing down the eating process Goal-setting Behavioral contracting and reinforcement Nutrition education and meal planning Modification of physical activity Social support Cognitive restructuring Problem-solving 1. Knowler WC, e t a l. N Engl J Me d. 2002;346(6): Diabe te s Pre ve ntio n Pro gram Re se arch Gro up. Lancet Diabetes Endocrinol (11): Lo o k A HE A D R e se a rch Gro u p. Obesity. 2014;22:5-13 Je n se n MD, e t a l. Circulation 2014;129:S102-S

11 38 behavioral treatment trials Average baseline BMI: 31.9 kg/m 2 Overweight adults with intervention sessions in year 1 lost 6% baseline weight Control groups lost little or no weight Patient education sessions: Healthy diet choices Physical activity Weight loss goals Barriers to weight loss Regular weight checks Peer support Antihistamines Steroids Hypoglycemic agents Estrogens Beta blockers Calcium channel blockers Some antidepressants Anticonvulsants/mood stabilizers Migraine medications Atypical antipsychotics HIV medications Chemotherapy Do me cq JP, e t al. J Clin Endocrinol Me ta b. 2015;100: /j c #sthash.sT2 TK9 LY.dpuf Le B l a n c E, e t a l. Ann Intern Med 2011;155:434. Short-term adjunct to comprehensive regimen in management of exogenous obesity with initial BMI 30 kg/m 2 or 27 kg/m 2 in the presence of other risk factors (eg, diabetes, hyperlipidemia, controlled hypertension). History of CVD, uncontrolled hypertension, during or within 14 days of using MAO inhibitors, glaucoma, agitated states, pregnancy, breastfeeding, drug abuse history, known hypersensitivity, or idiosyncrasy to the sympathomimetic amines. Not recommended for use in pediatric patients 16 years. Cardiac: Pulmonary hypertension and/or regurgitant cardiac valvular disease, palpitation, tachycardia, elevated blood pressure, ischemic events, CN S: overstimulation, restlessness, dizziness, insomnia, euphoria, dysphoria, tremor, headache, psychosis GI: Dryness of the mouth, unpleasant taste, diarrhea, constipation, other gastrointestinal disturbances Other: urticaria, impotence, libido changes Dosage should be individualized to obtain an adequate response with the lowest effective dose. The usual adult dose is 1 tablet TID ½ hour before meals. Tablet is scored to facilitate administering one half of the usual dosage for patients not requiring the full dose. Caution patients about potential to impair ability to operate machinery or drive a vehicle. Obesity Chronic management, including weight loss and weight maintenance, when used in conjunction with a reduced-calorie diet; to reduce the risk for weight regain after prior weight loss. Le xi co mp malabsorption syndrome, pregnancy, breastfeeding, cholestasis, some medications (ex. warfarin, antiepileptic agents, levothyroxine, cyclosporine) Bragg R, et al. J Am Assoc Nurse Pract 2016;28: Oily spotting, cramps, BMI, calorie/fat flatus with discharge, intake; serum fecal urgency, fatty oily stool, increased defecation, fecal incontinence glucose in patients with diabetes; thyroid function in patient with thyroid disease; liver function tests in patients exhibiting symptoms of hepatic impairment; renal function in patients at risk for renal impairment. Adjunct to comprehensive regimen in management of exogenous obesity with initial BMI 30 kg/m 2 or 27 kg/m 2 in the presence of at least weightrelated comorbidit y. Pregnancy and breastfeeding, hyperthyroidism, glauco ma, during/within 14 days of taking monoamine oxidase inhibitors Risk Evaluation and Mitigation Strategy Paresthesiasdizziness, taste alterations, insomnia, constipation, dry mouth, elevation in heart rate, memory or cognitive changes Bragg R, et al. J Am Assoc Nurse Pract 2016;28: Seizure frequency, hydration status, electrolytes,serum creatinine, sympt oms of acute acidosis, ammonia level in patients with unexplained lethargy, vomiting, or mental status changes; intraocular pressure, suicidality, weight + eating behaviors in patients with eating disorder symptoms/risk factors Adjunct to a reducedcalorie diet and increased physical activity for chronic weight management in adults with an initial BMI of 30 kg/m 2 or 27 kg/m 2 in the presence of at least one weight-related comorbid condition (eg, hypertension, type 2 diabetes mellitus, and/or dyslipidemia) Uncontrolled hypertension, seizure disorder, anorexia or bulimia, drug or alcohol withdrawal, chronic opioid use, monamine oxidase inhibitors Nausea, constipation, headache, dizziness, vomiting, insomnia, dry mouth Bragg R, et al. J Am Assoc Nurse Pract 2016;28: Transient increase in blood pressure Blood pressure and heart rate; blood glucose; weight; BMI; renal and liver function; mental status for depression, suicidal ideation, anxiety, social functioning, mania, and panic attacks. 11

12 Chronic weight management, as an adjunct to a reducedcalorie diet and increased physical activity, in adults with either an initial body mass index (BMI) of 30 kg/m 2 or an initial BMI of 27 kg/m 2 and at least one weight-related comorbid condition (eg, hypertension, dyslipidemia, type 2 diabetes). Pregnancy, breastfeeding Caution with serotoninergic agents (due to risk of serotonin syndrome) Avoid in patients w/severe hepatic or renal insufficiency, valvular heart disease Headache, dizziness, fatigue, nausea, dry mouth, cough, and constipation Patients w/t2dm, back pain, cough, hypoglycemia Bragg R, et al. J Am Assoc Nurse Pract 2016;28: Weight, waist circumference; CBC; blood glucose (if diabetes); prolactin; depression and/or suicidal thoughts/behavior; signs/symptoms of SS/NMS-like reaction; signs/symptoms of valvular heart disease (dyspnea, dependent edema) As an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial BMI of 30 kg/m 2 or greater (obese) or 27 kg/m 2 or greater (overweight) in the presence of at least 1 weight-related comorbid condition (eg, hypertension, type 2 diabetes mellitus, dyslipidemia) Medullary thyroid cancer history, multiple endocrine neoplasia type 2 history, history of pancreatitis, pregnancy, breastfeeding Risk Evaluation and Mitigation Strategy Nausea, vomiting, diarrhea, constipation, hypoglycemia in patients with T2DM, increased lipase, increased heart rate, pancreatitis Plasma glucose, HbA1c, renal function; signs/symptoms of pancreatitis; emergence of worsening depression, suicidal thoughts/behavior, changes in behavior; heart rate; body weight (at week 16 when used for chronic weight management) Bragg R, et al. J Am Assoc Nurse Pract 2016;28:107-15; Kahan S. Am J Ma n a g Care. 2016;22:S186-S196 Phentermine Drug Advantages Disadvantages Inexpensive Weight loss >3-5% Toperimate/phentermine Weight loss >5% Lorcaserin Orlistat Orlistat OTC Nonsystemic Inexpensive Natrexone/bupropion Weight loss 3-5% Food addiction Liraglutide Apovian CM, et al. J Clin Endocrinol Me ta b 2015;100: No long-term data Expensive Teratogen Expensive Weight loss 3-5% Weight loss 2-3% Mid-level price range Expensive Injectable 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): Bays HE, Seger JC, Primack C, McCarthy W, Long J, Schmidt SL, Daniel S, Wendt J, Horn DB, Westman EC: Obesity Algorithm, presented by the Obesity Medicine Association Bragg R, Crannage E. Review of pharmacotherapy options for the management of obesity. J Am AssocNurse Pract. 2016;28(2): Bray GA, Fruhbeck G, Ryan DH, Wilding JP. Management of obesity. Lancet. 2016;387(10031): Bray GA, Ryan DH. Medical therapy for the patient with obesity. Circulation. 2012;125(13): Chou W-yS, Prestin A, Kunath S. Obesity in social media: a mixed methods analysis. Translat ional Behavioral Medicine. 2014;4(3): Dietrich MO, Horvath TL. Limitations in anti-obesity drug development: the critical role of hunger-promoting neurons. Nat Rev Drug Discov. 2012;11(9): Dobkin BH. Wearable motion sensors to continuously measure real-world physical activities. Current Opinion in Neurology. 2013;26(6): FlegalKM, Kruszon-Moran D, Carroll MD, et al. Trends in Obesit y Among Adult s in t he Unit ed States, 2005 to JAMA. 2016;315(21): 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: Golden A. Obesity. In A. Hollier (Ed.), Clinical Guidelines in Primary Care. pp , 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): Jensen MD, Ryan DH, Apovian CM, et al 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. LeBlanc E, O Connor E, Whitlock EP, et al. Effectiveness of primary care-relevant treatments fo r o be sit y in adult s: A syst e mic e vide nce re vie w fo r t he US Pre ve nt ive Se rvice s Task F o rce. Ann Intern Med. 2011;155(7):434 Lock e AE, Kahali B, Berndt SI, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518(7538): Mozaffarian D. Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review. Circulation. 2016;133(2): 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): Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, JAMA. 2014;311(8): Rubino F, Nathan D, EckelRH, et al. Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations. Diab Care. 2016;39(6): Sumithran P, Prendergast LA, Delbridge E, et al. Long-Term Persist ence of Hormonal Adaptations to Weight Loss. New England Journal of Medicine. 2011;365(17): Suzuki K, Jayasena CN, Bloom SR. Obesity and Appetite Control. Experimental Diabetes Research. 2012;2012: VallisM, Piccinini Vallis H, Sharma AM, FreedhoffY. Modified 5 As: Minimal intervention for obesity counseling in primary care. Canadian Family Physician. 2013;59(1): VilsbollT, Christ ensen M, Junk er AE, et al. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised cont rolled trials. BMJ. 2012;344:d7771. YanovskiSZ, YanovskiJA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014;311(1):

13 Diabetes Prevention Program 1 LOOK AHEAD 3 Without Background Multi-center trial in patients with impaired glucose tolerance Weight loss of 7% reduced the rate of progression from impaired glucose tolerance to diabetes by 5% Reduced risk factors for CVD over 15 years ethically diverse overweight/obese adults w/t2dm Year 1: 5% weight loss in 68% who received intensive lifestyle counseling vs 13.3% who received usual care Year 8: 5% weight loss in 50.5% who received intensive lifestyle counseling vs 35.7% who received usual care 1. Knowler WC, e t a l. N Engl J Me d. 2002;346(6): Diabe te s Pre ve ntio n Pro gram Re se arch Gro up. Lancet Diabetes Endocrinol (11): Lo o k A HE A D R e se a rch Gro u p. Obesity. 2014;22:5-13 Self-monitoring e.g., food diaries Controlling or modifying the stimuli that activate eating Slowing down the eating process Goal-setting Behavioral contracting and reinforcement Nutrition education and meal planning Modification of physical activity Social support Cognitive restructuring Problem-solving 38 behavioral treatment trials Average baseline BMI: 31.9 kg/m 2 Overweight adults with intervention sessions in year 1 lost 6% baseline weight Control groups lost little or no weight Patient education sessions: Healthy diet choices Physical activity Weight loss goals Barriers to weight loss Regular weight checks Peer support Je n se n MD, e t a l. Circulation 2014;129:S102-S138. Le B l a n c E, e t a l. Ann Intern Med 2011;155:434. Antihistamines Steroids Hypoglycemic agents Estrogens Beta blockers Calcium channel blockers Some antidepressants Anticonvulsants/mood stabilizers Migraine medications Atypical antipsychotics HIV medications Chemotherapy Do me cq JP, e t al. J Clin Endocrinol Me ta b. 2015;100: /j c #sthash.sT2 TK9 LY.dpuf Short-term adjunct to comprehensive regimen in management of exogenous obesity with initial BMI 30 kg/m 2 or 27 kg/m 2 in the presence of other risk factors (eg, diabetes, hyperlipidemia, controlled hypertension). History of CVD, uncontrolled hypertension, during or within 14 days of using MAO inhibitors, glaucoma, agitated states, pregnancy, breastfeeding, drug abuse history, known hypersensitivity, or idiosyncrasy to the sympathomimetic amines. Not recommended for use in pediatric patients 16 years. Cardiac: Pulmonary hypertension and/or regurgitant cardiac valvular disease, palpitation, tachycardia, elevated blood pressure, ischemic events, CN S: overstimulation, restlessness, dizziness, insomnia, euphoria, dysphoria, tremor, headache, psychosis GI: Dryness of the mouth, unpleasant taste, diarrhea, constipation, other gastrointestinal disturbances Other: urticaria, impotence, libido changes Dosage should be individualized to obtain an adequate response with the lowest effective dose. The usual adult dose is 1 tablet TID ½ hour before meals. Tablet is scored to facilitate administering one half of the usual dosage for patients not requiring the full dose. Caution patients about potential to impair ability to operate machinery or drive a vehicle. 13

14 Obesity Chronic management, including weight loss and weight maintenance, when used in conjunction with a reduced-calorie diet; to reduce the risk for weight regain after prior weight loss. malabsorption syndrome, pregnancy, breastfeeding, cholestasis, some medications (ex. warfarin, antiepileptic agents, levothyroxine, cyclosporine) Oily spotting, cramps, BMI, calorie/fat flatus with discharge, intake; serum fecal urgency, fatty oily stool, increased defecation, fecal incontinence glucose in patients with diabetes; thyroid function in patient with thyroid disease; liver function tests in patients exhibiting symptoms of hepatic impairment; renal function in patients at risk for renal impairment. Adjunct to comprehensive regimen in management of exogenous obesity with initial BMI 30 kg/m 2 or 27 kg/m 2 in the presence of at least weightrelated comorbidit y. Pregnancy and breastfeeding, hyperthyroidism, glauco ma, during/within 14 days of taking monoamine oxidase inhibitors Risk Evaluation and Mitigation Strategy Paresthesiasdizziness, taste alterations, insomnia, const ipat ion, dry mouth, elevation in heart rate, memory or cognitive changes Seizure frequency, hydration status, electrolytes,serum creat inine, symptoms of acute acidosis, ammonia level in patients with unexplained lethargy, vomiting, or mental status changes; intraocular pressure, suicidality, weight + eating behaviors in patients with eating disorder symptoms/risk factors Le xi co mp Bragg R, et al. J Am Assoc Nurse Pract 2016;28: Bragg R, et al. J Am Assoc Nurse Pract 2016;28: Adjunct to a reducedcalorie diet and increased physical activity for chronic weight management in adults with an initial BMI of 30 kg/m 2 or 27 kg/m 2 in the presence of at least one weight-related comorbid condition (eg, hypertension, type 2 diabetes mellitus, and/or dyslipidemia) Uncontrolled hypertension, seizure disorder, anorexia or bulimia, drug or alcohol withdrawal, chronic opioid use, monamine oxidase inhibitors Nausea, constipation, headache, dizziness, vomiting, insomnia, dry mouth Bragg R, et al. J Am Assoc Nurse Pract 2016;28: Transient increase in blood pressure Blood pressure and heart rate; blood glucose; weight; BMI; renal and liver function; mental status for depression, suicidal ideation, anxiety, social functioning, mania, and panic attacks. Chronic weight management, as an adjunct to a reducedcalorie diet and increased physical activity, in adults with either an initial body mass index (BMI) of 30 kg/m 2 or an initial BMI of 27 kg/m 2 and at least one weight-related comorbid condition (eg, hypertension, dyslipidemia, type 2 diabetes). Pregnancy, breastfeeding Caution with serotoninergic agents (due to risk of serotonin syndrome) Avoid in patients w/severe hepatic or renal insufficiency, valvular heart disease Headache, dizziness, fatigue, nausea, dry mouth, cough, and constipation Patients w/t2dm, back pain, cough, hypoglycemia Bragg R, et al. J Am Assoc Nurse Pract 2016;28: Weight, waist circumference; CBC; blood glucose (if diabetes); prolactin; depression and/or suicidal thoughts/behavior; signs/symptoms of SS/NMS-like reaction; signs/symptoms of valvular heart disease (dyspnea, dependent edema) As an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial BMI of 30 kg/m 2 or greater (obese) or 27 kg/m 2 or greater (overweight) in the presence of at least 1 weight-related comorbid condition (eg, hypertension, type 2 diabetes mellitus, dyslipidemia) Medullary thyroid cancer history, multiple endocrine neoplasia type 2 history, history of pancreatitis, pregnancy, breastfeeding Risk Evaluation and Mitigation Strategy Nausea, vomiting, diarrhea, constipation, hypoglycemia in patients with T2DM, increased lipase, increased heart rate, pancreatitis Plasma glucose, HbA1c, renal function; signs/symptoms of pancreatitis; emergence of worsening depression, suicidal thoughts/behavior, changes in behavior; heart rate; body weight (at week 16 when used for chronic weight management) Bragg R, et al. J Am Assoc Nurse Pract 2016;28:107-15; Kahan S. Am J Ma n a g Care. 2016;22:S186-S196 Phentermine Drug Advantages Disadvantages Inexpensive Weight loss >3-5% Toperimate/phentermine Weight loss >5% Lorcaserin Orlistat Orlistat OTC Nonsystemic Inexpensive Natrexone/bupropion Weight loss 3-5% Food addiction Liraglutide No long-term data Expensive Teratogen Expensive Weight loss 3-5% Weight loss 2-3% Mid-level price range Expensive Injectable Apovian CM, et al. J Clin Endocrinol Me ta b 2015;100: