A H o l i s t i c P re s c r i p t i o n t o A ddre s s O b e s i t y

Transcription

1 A H o l i s t i c P re s c r i p t i o n t o A ddre s s O b e s i t y A N N E D A LY, R D N, B C - A D M, C D E G AY L E J E N N I N G S, R D N, B C - A D M, C D E S I U C E N T E R F O R F A M I LY M E D I C I N E S N E H A B A X I S R I VA S TAVA, P H A R M D, B C A C P, C D E R O S A L I N D F R A N K L I N U N I V E R S I T Y O F S C I E N C E A N D M E D I C I N E C O L L E G E O F P H A R M A C Y

2 Disclosure and Conflict of Interest Dr. Sneha Srivastava No disclosure or conflict of interest to report Anne Daly No disclosure or conflict of interest to report Gayle Jennings No disclosure or conflict of interest to report 2

3 Objectives: Describe appropriate lifestyle interventions for obesity. Discuss how IBT can be implemented in a health care clinic. Discuss evidence-based medicinal approaches for weight loss in pre-diabetes and diabetes. Select and recommend appropriate medication therapy for obesity. 3

4 Meet Chad Chad is a 35 year old male presenting to clinic for routine follow-up. PMH: T2DM x 5 years, uncontrolled hypertension, hyperlipidemia, hyperthyroidism Vitals BP: 148/92 HR: 98 Height: 5 10 Weight: 220 lbs. Waist circumference: 45 in BMI: 31.6 kg/m 2 Current Medications Metformin 1000 mg by mouth twice daily Albiglutide 50 mg by SQ injection daily Amlodipine 5 mg by mouth twice daily Metoprolol succinate 100 mg by mouth daily Atorvastatin 80 mg by mouth daily Allergies: lisinopril (angioedema), losartan (hyperkalemia) Labs: CMP normal except SCr: 1.52 mg/dl CrCl: 59 ml/min A1c: 7.5% 4

5 Question 1: ACCORDING TO THE AHA/ACC/TOS GUIDELINES, WHICH RISK STRATIFICATION CATEGORY DOES CHAD FALL INTO, BASED ON HIS BMI? A. Overweight B. Class I Obesity C. Class II Obesity D. Class III Obesity 5

6 Question 2: ACCORDING THE SPECIFICS OF CHAD S CASE, WHICH OF THE FOLLOWING AGENTS WOULD BE THE MOST APPROPRIATE THERAPY FOR CHAD TO TRIAL IN WEIGHT MANAGEMENT? A. Phentermine/topiramate (Qsymia ) B. Liraglutide (Victoza ) C. Naltrexone/bupropion (Contrave ) D. Lorcaserin (Belviq ) 6

7 Question 3: WHAT TYPE OF MONITORING SHOULD BE DONE BY YOU, THE CLINICIAN, AND AT WHAT INTERVAL? A. Educate Chad to decrease his calories to < 800kcals/day, take the medication as prescribed and follow up in 6 months for a 20% weight loss. B. Refer of enroll in an intensive behavior therapy (IBT). C. Educate Chad to follow-up in 3 months with a goal weight loss of 11 pounds, evaluate his weight, BMI, waist circumference, and side effects from the medication. D. Add rapid acting insulin QID, continue all medications and call him in 3 months to get A1c and BMI evaluated then can decide about starting the patient on dual agents for weight loss. 7

8 THE RISE IN INCIDENCE 8 CDC Diabetes Statistics Accessed 3/24/16

9 OBESITY AND DIABETES PREVALENCE OBESITY: 2016 DIABETES:

10 AVAILABLE CLINICAL OBESITY GUIDELINES Group Release Date Document Name AHA/ACC/TOS 2013 Guideline for the Management of Overweight and Obesity in Adults AACE/ACE 2017 Clinical Practice Guidelines for Comprehensive Medical Care of Patients with Obesity ADA 2017 Standards of Medical Care in Diabetes, 2017 Obesity Management for Treatment of Type 2 Diabetes AHA: American Heart Association ACC: American College of Cardiology TOS: The Obesity Society AACE: American Association of Clinical Endocrinologists ACE: American College of Endocrinology ADA: American Diabetes Association 10 J Am Coll Cardiol Jul 1: 63(25 Pt B): Endocr Pract May 24. [Epub ahead of print] Diabetes Care 2016 Jan; 39 (Supplement 1): S47-S51

11 GUIDELINE RECOMMENDATIONS Guideline AHA/ACC/TOS AACE/ACE ADA Screening (Height, weight, and BMI) Waist Circumference (BMI < 35 kg/m 2, increased risk:) Risk Stratification (BMI [kg/m 2 ]) Weight Loss Pharmacotherapy (BMI [kg/m 2 ]) Bariatric Surgery (BMI [kg/m 2 ]) Annually or more frequently Annually Each patient encounter Women: > 88 cm or > 35 in Men: > 102 cm or > 40 in Overweight: > Class I Obese: 30 to < 35 Class II Obese: 35 to Class III Obese (Extreme Obesity): % baseline weight reduction within 6 months BMI 30 or BMI 27 + obesityassociated comorbidity* BMI 40 w/out comorbidity BMI 35 + obesityassociated comorbidity Prevention of diabetes: 10% (other recommendation based on comorbid disease states) BMI 40 w/out complication BMI 35 + severe complication BMI (consideration) BMI = Body Mass Index (kg/m 2 ) WC = Waist Circumference T2DM = type 2 diabetes mellitus *Comorbidities: hypertension, hyperlipidemia, prediabetes, or diabetes BMI 27 No recommendation Overweight: Obese: Extreme obesity: 40 5% reduction for overweight & obese patients with T2DM BMI > 35 and T2DM 11 J Am Coll Cardiol Jul 1: 63(25 Pt B): Endocr Pract May 24. [Epub ahead of print] Diabetes Care 2016 Jan; 39 (Supplement 1): S47-S51

12 T R E AT M E N T S T R AT E G I E S

13 Lifestyle Modifications High-intensity comprehensive weight loss interventions: Moderately-reduced calorie diet An energy deficit of 500 kcal/day Women: 1,200-1,500 kcal/day Men: 1,500 to 1,800 kcal/day Increased physical activity Aerobic physical activity (brisk walking) for >150 minutes/week No more than 90 minutes at a time of inactivity Intensive behavior therapy Evidence based dietary interventions Motivational interviewing recommended Frequent contact 13 Position of Academy of Nutrition & Dietetics 2016 J Am Coll Cardiol Jul 1: 63(25 Pt B): Diabetes Care 2016 Jan; 39 (Supplement 1): S23-S35

14 MEDICARE INTENSIVE BEHAVIORAL THERAPY (IBT) FOR OBESITY Effective Nov 2011, CMS started this new benefit Includes: obesity screening using BMI, dietary assessment, IBT counseling to promote sustained wt loss using high intensity interventions diet and exercise IBT specifies very clearly: diagnostic codes, provider specialty types (primary care listed), billing and coding procedures

15 MEDICARE: PATIENT ELIGIBILITY Ages 18 and up Must be Medicare B beneficiaries Good news: other insurance providers are covering this! BMI > 30 Competent and alert at time service provided Academy of Nutrition And Dietetics. Intensive Behavioral Therapy for Obesity. 2017

16 ELIGIBLE PRIMARY CARE PROVIDERS Multidisciplinary team based approach encouraged MDs, PAs, NPs may bill for services RDNs can work with above providers incident to physician services, as auxiliary personnel under PCPs direct supervision. MD must be present in office suite when RDN performing service Academy of Nutrition And Dietetics. Intensive Behavioral Therapy for Obesity. 2017

17 VISIT FREQUENCY Month 1: weekly 1:1 visits Month 2-6: 1:1 visits every other week At month 6, if Pt has lost at least 3 kg (6.6 lb), Pt may continue treatment Month 7-12: 1:1 visits once monthly If Pt does not meet minimum wt loss 6 M, PCP must wait 6 M, then reassess Pt readiness to change & BMI. If Pt meets criteria for treatment, PCP may re-administer 1 st 6 M of program NOTE: Pt cannot receive > 22 visits in 12 M; so restart date should be 12 M from original start date Academy of Nutrition And Dietetics. Intensive Behavioral Therapy for Obesity. 2017

18 PATIENT FLOW IN CLINIC MD: Patient presents for Annual Wellness Visit Patient s BMI > 30, MD includes diagnosis in assessment If patient is interested, MD refers to RDN Scheduling: Pt referred for initial appointment with RDN Task is sent to referral coordinator for eligibility and verification RDN: Assesses pt and documents in EMR RDN schedules fu appointments and tracks outcomes RDN sends communication to MD regarding patient s progress Academy of Nutrition & Dietetics: Intensive Behavioral Therapy for Obesity: Putting It Into Practice

19 VISIT FREQUENCY Medicare will pay for G0447 and G0473 with appropriate ICD-10 code, no more than 22 times in a 12-month period. Don t overthink it. Keep the visits are short/brief. Month 1: weekly 1:1 visits Month 2-6: 1:1 visits every other week At month 6, if Pt has lost at least 3 kg (6.6 lb), Pt may continue treatment Month 7-12: 1:1 visits once monthly If Pt does not meet minimum wt loss 6 M, PCP must wait 6 M, then re-assess Pt readiness to change & BMI. If Pt meets criteria for treatment, PCP may re-administer 1 st 6 M of program NOTE: Pt cannot receive > 22 visits in 12 M; so restart date should be 12 M from original start date Academy of Nutrition And Dietetics. Intensive Behavioral Therapy for Obesity. 2017

20 DETERMINING READINESS TO CHANGE LIFESTYLE FACTORS CONSIDERED Reasons for wanting to lose weight Adequate support from family & friends Patient perception of benefits (ie, realistic expectations)and risks of weight loss Patient attitudes toward making food changes and increasing physical activity strong willingness needed Barriers, including time, transportation, work schedule, finances Mental health: major depression is poor prognostic indicator for weight loss Serious previous wt loss attempts without results

21 HOW CAN I HELP MY PATIENTS SET GOALS? Ask your patients: Is your weight a concern to you? How so? How often is your weight a concern to you? What are your goals regarding your weight? What kind of changes would you be willing to start with? Who do you rely on for support? Are you expecting them to support your goals to lose weight? What kind of help would you like from me in regards to your weight? 21

22 5-A FRAMEWORK FOR OBESITY INTERVENTION Assess Arrange Advise Assist Agree Academy of Nutrition And Dietetics. Intensive Behavioral Therapy for Obesity. 2017

23 MEDICARE IBT BILLING Must use ICD-10 Codes: Z68.30-Z68.39, Z68,41-Z68.45 Use obesity diagnosis code in medical chart before IBT began; continue to use this BMI Z-code throughout program, despite BMI decreasing Medicare will pay for G0447 (individual) and G0473 (group) with appropriate ICD-10 code Can bill no more than 22 visits in 12 month period G0447 and G0473 are time-based codes; 1 unit G0447 is 15 minutes; 1 unit G0473 is 30 minutes Most RDNs doing IBT report reimbursement limited to 1 unit per day of service AND IBT Toolkit includes information on contacting your MAC and summary of information AND has obtained from MACs While payments to individual clinicians will vary with geography, 2016 general rate of reimbursement is approximately $25 for each 15 min counseling session 23

24 DOCUMENTATION REQUIREMENTS Weight and BMI at every visit Start and end time of sessions PCP must co-sign every RDN progress note Academy of Nutrition And Dietetics. Intensive Behavioral Therapy for Obesity. 2017

25 E-HEALTH, COMPUTER & SMART PHONE INTERVENTIONS Can decrease intervention costs and increase reach Computer based programs > 6 M duration produced greater weight loss than minimal interventions but face to face produced greater wt loss than computer based interventions Smart phones theorized to have greater potential; can maintain accountability, feedback, social support without face time; is new area of research in wt management 25

26 PRACTICE PEARLS FROM SIU CENTER FOR FAMILY MEDICINE Group and individual appointments are allowed; no groups allowed for FQHCs Telehealth is allowed, but not in FQHCs Talk to your billing department before and after your IBT services are provided; use them as a resource to support you The Academy of Nutrition and Dietetics has a toolkit available for download: Intensive Behavioral Therapy for Obesity: Putting it into Practice Use it! 26

27 KEY RDN TAKE-A-WAYS ABOUT IBT Need identify MD champion Opportunity to elevate role of RDN in physician practice Aligns well with Patient Centered Medical Home Supports Strategic Plans of organizations Doing what is RIGHT for patient care Academy of Nutrition & Dietetics Intensive Behavioral Therapy for Obesity 2017

28 BENEFITS OF IMPLEMENTING IBT FOR OBESITY INTO MEDICAL SETTING Increased visibility/collaboration between RDN and PCP; promotes more referrals for other chronic conditions, ie, diabetes Increased access to appropriate patients Increased reimbursement and business Improved health for the patient Increased patient satisfaction 28

29 METABOLIC SURGERY AHA/ACC/TOS AACE/ACE ADA BMI 40 w/out comorbidity BMI 35 + obesityassociated comorbidity Roux-en-Y gastric bypass Sleeve gastrectomy Gastric band BMI 40 w/out complication BMI 35 + severe complication BMI (consideration) Types of Metabolic Surgery BMI > 35 and T2DM Biliopancreatic diversion with duodenal switch gastric bypass 29 Surg Obes Relat Dis Mar-Apr;12(3):468-95

30 METABOLIC SURGERY Advantages Sjostrom: Normalization of glycaemia 2 years following surgery in 72% of patients As compared with 16% in a matched control group treated with lifestyle and pharmacological interventions Schauer: 3 year study in obese patients with uncontrolled type 2 diabetes, A1c targets achieved by: 38% (P < 0.001) in the gastric bypass group 24% (P = 0.01) in the sleeve gastrectomy group 5% in pharmacologically treated group Disadvantages 30-day mortality rates: 0.2% for laparoscopic procedures and 2.1% for open procedures Long-term concerns: dumping syndrome (nausea, colic, diarrhea), vitamin and mineral deficiencies, osteoporosis, and, severe hypoglycemia from insulin hypersecretion (rare) 30 JAMA 2014;311: N Engl J Med 2014;370: Surgery 2007;142: Diabetes Care 2016 Jan; 39 (Supplement 1): S47-S51

31 NORADRENERGIC AGONISTS Diethylpropion CIV (Tenuate, Tenuate Dospan ) Phendimetrazine CIII (Bontril PDM ) Benzphetamine CIII (Didrex, Regimex ) Phentermine CIV (Adipex-P, Suprenza ) Discussed later 31

32 NORADRENERGIC AGONISTS FDA Indication Short-term (< 12 weeks) adjunct in a regimen of weight reduction based on caloric restriction Diethylpropion and benzphetamine: BMI 30 kg/m 2 Phendimetrazine: BMI 30 kg/m 2 or 27 kg/m 2 with risk factors Who have not responded to appropriate weight reducing regimen (diet and/or exercise) alone Dosing Diethylpropion IR: 25 mg by mouth three times daily one hour before meals ER: 75 mg by mouth once mid-morning Phendimetrazine 105 mg by mouth once daily minutes before morning meal Benzphetamine mg by mouth in the morning, may increase to three times daily Renal dosing No data, caution in patients with renal impairment Diethylpropion. Aventis Pharmaceuticals, Inc.; 2003 Phendimetrazine. Epic Pharma, LLC; 2011 Benzphetamine. Pfizer; 2009 *IR/ER: immediate/extended-release 32 Accessed 6/02/2016

33 NORADRENERGIC AGONISTS MOA: sympathomimetic amine, similar to amphetamines. Weight reduction likely mediated by the release of catecholamine (norepinephrine) in the hypothalamus resulting in decreased appetite and food intake, but other metabolic effects may also be involved. Absorption* Rapid uptake from gastrointestinal tract Lends to dosing recommendation of 60 minutes prior to meals *Pharmacokinetic data for Diethylpropion (Tenuate ) Qsymia. Vivus, Inc.; 2014 Diethylpropion. Aventis Pharmaceuticals, Inc.; 2003

34 NORADRENERGIC AGONISTS Adverse Effects Increased blood pressure, palpitations, urticaria, constipation, nausea, xerostomia, unpleasant taste, dizziness, insomnia, tremor, restlessness, or changes in libido Contraindications Pregnancy (category X*) or breastfeeding, cardiovascular disease, glaucoma, hyperthyroidism, agitated state, drug abuse, glaucoma, hypersensitivity to sympathomimetic amines, arteriosclerosis Drug Interactions Monoamine oxidase inhibitors (during or within 14 days of use) and tricyclic antidepressants Antihypertensive agents Concomitant use of other anorectics or central nervous system stimulants Monitoring Weight loss, cardiac/echo evaluation for pre-existing/post-treatment development of complications *Category X: benzphetamine and phendimetrazine Category B: diethylpropion 34 Diethylpropion. Aventis Pharmaceuticals, Inc.; 2003 Phendimetrazine. Epic Pharma, LLC; 2011 Benzphetamine. Pfizer; Accessed 6/02/16

35 A comparative study of five centrally acting drugs on the pharmacological treatment of obesity H Suplicy, CL Boguszewski, CMC dos Santos, M do Desterro de Figueiredo, DR Cunha and R Radominski 2014 a. FDA indicated for weight loss b. Removed from the market c. FDA indicated for depression d. Not available in the U.S. 35 Int J Obes (Lond) Aug;38(8):

36 PHENTERMINE CIV Adipex-P, Suprenza Dosing Adipex-P 37.5 mg by mouth daily, administered before breakfast or 1-2 hours after Suprenza 15 mg/30 mg/37.5 mg ODT in the morning with or without food Renal Dosing No studies have been completed, caution in patients with renal impairment ODT = Orally disintegrating tablet 36 Suprenza (phentermine hydrochloride) ODT. Akrimax Pharmaceuticals, LLC; Adipex-P (phentermine hydrochloride USP) for oral use. Teva Pharmaceuticals USA; 2012.

37 PHENTERMINE MOA: sympathomimetic amine, similar to amphetamines Absorption Rate and extent similar across formulations ODT formulation absorption decreased: ~5% when taken with a high-fat/calorie meal ~7% if swallowed without prior disintegration Distribution 17.5% protein bound Metabolism Hepatic via hydroxylation and N-oxidation CYP3A4 substrate (not extensively metabolized) Elimination Primarily in the urine (62-85% unchanged) ODT = Orally disintegrating tablet 37 Adipex-P (phentermine hydrochloride USP) for oral use. Teva Pharmaceuticals USA; 2012.

38 PHENTERMINE Adverse Effects Cardiovascular (pulmonary hypertension, valvular disease, ischemic events, increased blood pressure), dizziness, insomnia, euphoria, gastrointestinal upset, erectile dysfunction or changes in libido Contraindications pregnancy (category X) and breastfeeding, cardiovascular disease, hyperthyroidism, glaucoma, agitate states, drug abuse, hypersensitivity to sympathomimetic amines Drug Interactions Monoamine oxidase inhibitors (during or within 14 days of use) Alcohol use Adrenergic neuron blocking drugs Insulin Monitoring Renal function 38 Adipex-P (phentermine hydrochloride USP) for oral use. Teva Pharmaceuticals USA; 2012.

39 WEIGHT LOSS OF PHENTERMINE VS. PLACEBO Kang 2010 Aronne 2013 WC = waist circumference 1 inch = 2.54 cm 39 Diabetes Obes Metab Oct;12(10): Obesity (Silver Spring) Nov;21(11):

40 PHENTERMINE/TOPIRAMATE EXTENDED- RELEASE CIV (QSYMIA ) FDA Indication Adjunct to a reduced-calorie diet and increased physical exercise for chronic weight management in adults with BMI of: 30 kg/m 2 or 27 kg/m 2 with one weight related comorbidity Dosing Titration schedule Renal dosing CrCl < 30 ml/min, do not exceed 7.5 mg/46 mg once daily dosing Hepatic Impairment Child-Pugh score 7 9, do not exceed 7.5 mg/46 mg once daily dosing CrCl = Creatinine clearance 40 Qsymia. Vivus, Inc.; 2014

41 INITIATION ESCALATION ER = extended-release QOD = every other day 41

42 PHENTERMINE/TOPIRAMATE EXTENDED- RELEASE (QSYMIA ) Topiramate ER MOA: suppression of appetite and enhanced satiety via: Augmentation of gamma-aminobutyric acid (GABA) activity Inhibition of excitatory glutamate receptors Carbonic anhydrase inhibition Modulation of voltage-gated ion channels Absorption Not affected when taken with a high-fat meal 42 Diabetes Metab Syndr Obes. 2013; 6: Qsymia. Vivus, Inc.; 2014 Qsymia (phentermine and topiramate). Retrieved from

43 PHENTERMINE/TOPIRAMATE EXTENDED- RELEASE (QSYMIA ) Adverse Effects Fetal toxicity, heart rate elevation, suicidal ideation/behavior, acute closed-angle glaucoma, mood and sleep disorders, cognitive impairment, metabolic acidosis Contraindications Pregnancy (category X) and breastfeeding, glaucoma, hyperthyroidism, hypersensitivity to other sympathomimetic amines Drug Interactions Monoamine oxidase inhibitors Central nervous system depressants (benzodiazepines, barbiturates, sleep agents) Non-potassium sparing diuretics Concurrent administration with: Other carbonic anhydrase inhibitors or antiepileptics Monitoring Baseline and periodic chemistry panel that includes bicarbonate, creatinine, potassium, and glucose 43 Qsymia. Vivus, Inc.; 2014

44 EQUIP, CONQUER, and SEQUEL Trials Efficacy and Safety of Phentermine/topiramate Extended-Release 44 Obesity (Silver Spring, Md). 2012;20(2): Lancet Apr 16;377(9774): Am J Clin Nutr Feb;95(2):

45 LORCASERIN (BELVIQ ) FDA Indication - Chronic weight management, as an adjunct to a reduced-calorie diet and increased physical activity in patients with: - BMI 30 kg/m 2 or 27 kg/m 2 with one weight related comorbidity (Hypertension, Type 2 Diabetes Mellitus, or Hyperlipidemia) Dosing - 10 mg by mouth twice daily - If 5% of body weight has not been lost after 12 weeks, discontinue Renal dosing - No renal dosing, use is not recommended if CrCl <30 ml/minute or in end stage renal disease 45 Lorcaserin. Arena Pharmaceuticals; 2012.

46 LORCASERIN (BELVIQ ) MOA: Lorcaserin is a selective serotonin 2C (5-HT(2C)) receptor agonist. The exact mechanism of action is not known, but lorcaserin is believed to promote satiety and decrease food intake by activating 5-HT(2C) receptors on anorexigenic pro-opiomelanocortin neurons in the hypothalamus Absorption Not affected by food consumption + Satiety - Food Consumption 46 Lorcaserin. Arena Pharmaceuticals; 2012.

47 LORCASERIN (BELVIQ ) Adverse Effects Headache, hypoglycemia, nausea, back pain, dizziness, fatigue, dry mouth Contraindications Pregnancy Drug Interactions Serotonin modulating agents (serotonin syndrome risk) CI with thioridazine (increased plasma levels of thioridazine) Increased risk of hypoglycemia with hypoglycemic agents Monitoring Serotonin syndrome, psychiatric/mood 47 changes, blood glucose, priapism Lorcaserin. Arena Pharmaceuticals; 2012.

48 BLOOM TRIAL ITT= Intention to Treat LOCF= Last Observed Carried Forward 48 N Engl J Med 2010; 363:24 J Clin Endocrinol Metab 96: ,

49 BLOOM TRIAL P value < 0.01 for twice daily vs. daily 49 N Engl J Med 2010; 363:24 J Clin Endocrinol Metab 96: ,

50 NALTREXONE/BUPROPION (CONTRAVE ) FDA Indication: adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of: 30 kg/m 2 or 27 kg/m 2 with one weight related comorbidity (Hypertension, Type 2 Diabetes, or Hyperlipidemia) Dosing: 8 mg naltrexone/90 mg bupropion by mouth according to chart below If 5% of body weight has not been lost after 12 weeks, discontinue Renal dosing No renal dosing, use is not recommended if CrCl <30 ml/minute or in ESRD 50 Naltrexone/bupropion ER. Orexigen; 2014.

51 NALTREXONE/BUPROPION (CONTRAVE ) MOA: Naltrexone, an opioid antagonist, and bupropion, a weak dopamine and norepinephrine reuptake inhibitor regulate food intake via effects on the hypothalamus (appetite regulatory center) and the mesolimbic dopamine circuit (reward system). Not completely understood Absorption Administration with a high-fat meal significantly increases systemic exposure to naltrexone and bupropion (AUC: 2.1-fold and 1.4-fold, respectively) TAKE ON EMPTY STOMACH Opioid antagonist DA/NE reuptake inhibitor 51 Naltrexone/bupropion ER. Orexigen; 2014.

52 NALTREXONE/BUPROPION (CONTRAVE ) Adverse Effects Nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea Contraindications Uncontrolled hypertension, seizure disorder, chronic opioid use, pregnancy, suicidal ideation/behavior Monitoring Renal function, blood pressure, and blood glucose Drug Interactions Monoamine oxidase inhibitors Drugs metabolized by and inducers/inhibitors of CYP2D6 Medications that lower the seizure threshold Dopaminergic drugs 52 Naltrexone/bupropion ER. Orexigen; 2014.

53 COR-II TRIAL NB32: Naltrexone/bupropion 32mg/360 mg Baseline BMI, NB32: 36.2, placebo: 36.1 P value <0.001 for each endpoint 53 Obesity (Silver Spring) May; 21(5):

54 COR-BMOD Baseline BMI NB32 + BMOD: 37.0 Placebo +BMOD: 36.3 NB32: Naltrexone/bupropion 32mg/360 mg BMOD: Behavioral Modifications P value <0.001 for each endpoint 54 Obesity (Silver Spring) Jan; 19(1): Obesity (Silver Spring) May; 21(5):

55 ORLISTAT (XENICAL OR ALLI ) FDA Indication Obesity management including weight loss/maintenance when used in conjunction with a reduced-calorie diet. Also indicated to reduce the risk for weight regain after prior weight loss Dosing 120 mg by mouth three times daily with each main meal containing fat (Xenical ) 60 mg by mouth three times daily with each main meal contatining fat (Alli ) Meals should be balanced consisting of approximately 30% fat Orlistat should be taken during or up to 1 hour after the meal Renal/Hepatic dosing No renal or hepatic dosing due to low systemic absorption 55 Xenical. Roche Laboratories, Inc. 2015

56 ORLISTAT (XENICAL OR ALLI ) MOA: A reversible inhibitor of gastric and pancreatic lipases, thus inhibiting absorption of dietary fats by 30%. Adverse Effects Oily spotting, flatus with discharge, fecal urgency, fecal incontinence Contraindications Pregnancy, chronic malabsorption syndrome, cholestasis Drug Interactions All patients should take a daily multivitamin that includes fat-soluble vitamins (A,D,E,K) and beta-carotene Cyclosporine, Levothyroxine, Warfarin, Amiodarone, Antiepileptic drugs Monitoring Body Mass Index, calorie and fat intake, GI intolerance 56 Xenical. Roche Laboratories, Inc. 2015

57 POOLED DATA FROM FIVE CLINICAL TRIALS P value < Xenical. Roche Laboratories, Inc. 2015

58 COMPARISON OF WEIGHT LOSS REGIMENS 58 REFERENCES: JAMA Intern Med. 2014;174(4): doi: /jamainternmed

59 GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONISTS MOA: Analogs of human glucagon-like peptide-1 (GLP-1) (an incretin hormone) which increases glucose-dependent insulin secretion, decreases inappropriate glucagon secretion, increases B-cell growth/replication, slows gastric emptying, and decreases food intake. Injectable therapy Weight Reduction: typically 2-3 kg depending on agent Safety Concerns: acute pancreatitis, medullary thyroid carcinoma, GI upset Place in therapy: One agent FDA approved for weight loss = Saxenda (liraglutide 3 mg), all other GLP1-agonists are only approved for type 2 diabetes 2nd line therapy for type 2 diabetes patients requiring % reduction in A1c Patient-specific factors, formulary, cost, and dosing schedule may affect therapy decision 59 Diabetes Care 2016 Jan; 39 (Supplement 1): S1-S111 Lexi-Comp Online. 2016

60 LIRAGLUTIDE (SAXENDA ) MOA: Glucagon-like-peptide 1 analog Indication: 30 kg/m 2 or 27 kg/m 2 with hypertension, type 2 diabetes, or hyperlipidemia Dosing: Pre-filled, multi-dose pens, can dial up to 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3 mg Initial dose of 0.6 mg under the skin daily, increasing by 0.6 mg every week until recommended dose of 3 mg is reached. Limitations of use: NOT indicated for type 2 diabetes Should not be used with insulin Should not be used with other GLP-1 agonist 60 Saxenda. Novo Nordisk. 2016

61 LIRAGLUTIDE (SAXENDA ) Adverse Reactions: Nausea, hypoglycemia, diarrhea, constipation, headache, abdominal pain Contraindications: Medullary Thyroid Carcinoma, Multiple Endocrine Neoplasia syndrome, Pregnancy Warnings/Precautions: Acute pancreatitis, acute gallbladder disease, heart rate increase Use caution initiating or escalating doses of liraglutide in those with renal impairment 61 Saxenda. Novo Nordisk. 2016

62 STUDY 1: OBESITY OR OVERWEIGHT WITH COMORBIDITY P values all < Saxenda. Novo Nordisk. 2016

63 SCALE TRIAL P values <0.001 for liraglutide 3.0 mg vs. placebo and 1.8 mg vs. placebo 46 JAMA. 2015;314(7): doi: /jama

64 SODIUM-GLUCOSE CO-TRANSPORTER 2 (SGLT2) INHIBITORS MOA: Lowers the renal threshold for glucose and increases urinary glucose excretion by interfering with the reabsorption of renally-filtered glucose across the tubular lumen of the proximal renal tubules Oral therapy Weight Reduction: 2-3 kg Safety Concerns: mycotic genital infection, UTI, dehydration/volume depletion Place in therapy: No current FDA indication for weight loss, may motivate patients to change lifestyle 2nd line therapy in type 2 diabetes patients requiring 0.5-1% reduction in A1c Patient-specific factors, formulary, and cost will affect therapy decision 64 Diabetes Care 2016 Jan; 39 (Supplement 1): S1-S111 Lexi-Comp Online. 2016

65 COST CONSIDERATIONS

66 INSURANCE COVERAGE OBESITY MEDICATIONS Coverage not always built into base plan Typically prior authorization required Must meet BMI indications: BMI > 30 or BMI > 27 in presence of at least one co-morbid condition (ie, DB, HTN, HLP) Employers can choose what is covered Employers with unions more likely to have coverage because members have requested it 66

67 COMMON COVERAGE OPTIONS Some employers have patients pay 50% as co-pay, with $250 cap; after that, employer pays in full Some have set co-pays, not a percent Some employers offer no caps, so patient continues to pay standard co-pay always 67

68 SAXENDA COVERAGE Approximately 50% Illinois plans provide some coverage; 50% offer no coverage Of Illinois plans with coverage: 0.4% have tier 1 9.9% have tier 2 35% have tier 3 0.8% have tier 4 List price Saxenda = $1100-$1200/month Websites: offers co-pay look up tool; enter name insurance, pt info www. saxendapro.com; coverage and reimbursement info, includes video with interactive tool to enter information and research coverage Toll free phone numbers also listed on website 68

69 WHO IN ILLINOIS HAS SAXENDA COVERAGE? State of Illinois largest employer; if have CVS Health pharmacy benefit with tier 2, co pay is about $50. Saxenda savings cards are available at that get that co-pay down to $35 for up to 2 yrs. Examples of other large employers offering coverage: Abbott Labs, American Airlines, Ameren, City of Chicago, Delta Airlines, Ford Motors, Edward Elmhurst, Advocate Health Care, John Deere. JP Morgan Chase, Lockheed Martin, VA National Formulary; (this is partial list only) Federal employees program does not currently cover Saxenda, but is pilot project underway to test effectiveness of Saxenda 69

70 Let s talk about Chad again Chad is a 35 year old male presenting to clinic for routine follow-up. PMH: T2DM x 5 years, uncontrolled hypertension, hyperlipidemia, hyperthyroidism Vitals BP: 148/92 HR: 98 Height: 5 10 Weight: 220 lbs. Waist circumference: 45 in BMI: 31.6 kg/m 2 Current Medications Metformin 1000 mg by mouth twice daily Albiglutide 50mg by SQ injection daily Amlodipine 5mg by mouth twice daily Metoprolol succinate 100mg by mouth daily Atorvastatin 80mg by mouth daily Allergies: Lisinopril (angioedema), Losartan (Hyperkalemia) Labs: CMP normal except SCr: 1.52 mg/dl CrCl: 59 ml/min A1c: 7.5% 70

71 Question 1: ACCORDING TO THE AHA/ACC/TOS GUIDELINES, WHICH RISK STRATIFICATION CATEGORY DOES CHAD FALL INTO, BASED ON HIS BMI? A. Overweight B. Class I Obesity C. Class II Obesity D. Class III Obesity 71

72 Question 2: ACCORDING THE SPECIFICS OF CHAD S CASE, WHICH OF THE FOLLOWING AGENTS WOULD BE THE MOST APPROPRIATE THERAPY FOR CHAD TO TRIAL IN WEIGHT MANAGEMENT? A. Phentermine/topiramate (Qsymia ) B. Liraglutide (Victoza ) C. Naltrexone/bupropion (Contrave ) D. Lorcaserin (Belviq ) 72

73 Question 3: WHAT TYPE OF MONITORING SHOULD BE DONE BY YOU, THE CLINICIAN, AND AT WHAT INTERVAL? A. Educate Chad to decrease his calories to < 800kcals/day, take the medication as prescribed and follow up in 6 months for a 20% weight loss. B. Refer of enroll in an intensive behavior therapy (IBT). C. Educate Chad to follow-up in 3 months with a goal weight loss of 11 pounds, evaluate his weight, BMI, waist circumference, and side effects from the medication. D. Add rapid acting insulin QID, continue all medications and call him in 3 months to get A1c and BMI evaluated then can decide about starting the patient on dual agents for weight loss. 73

74 SUMMARY Options are available for diabetes educators to utilize to help our patients lose weight. Lifestyle modification Metabolic surgery Intensive Behavior Therapy (IBT) per Medicare guidelines Medications Or a combination of these modalities 74

75 SPECIAL THANKS TO: Jessica L. Kerr, PharmD, CDE, Shelley Monroe and Jordan Sinclair, PharmD Southern Illinois University Edwardsville School of Pharmacy For content included in these slides. 75