What s the Skinny?: An Update on Medications for Weight Management

Transcription

1 What s the Skinny?: An Update on Medications for Weight Management Katura C. Bullock, PharmD, BCPS Associate Professor UNT System College of Pharmacy SESSION OBJECTIVES 1. Recognize the prevalence of obesity in the United States and its associated complications 2. Discuss recommended treatment options for the management of obesity 3. Compare the efficacy, side effects, cautions and warnings of medications approved for chronic management of obesity 4. Counsel patients on safe and effective use of supplements for obesity and weight loss downloaded from 1

2 OBESITY Is a chronic disease characterized by pathophysiological processes that result in increased adipose tissue mass and which can result in increased morbidity and mortality. Adult population Annual screening Quality measure for clinicians in the U.S. Diagnosis Anthropometric measurement Clinical descriptors The 2014 AACE/ACE Consensus Conference on Obesity ADULT OBESITY RATE BY STATE, 2014 PREVALENCE OF OBESITY AMONG U.S. ADULTS, AGED downloaded from 2

3 CLASSIFICATION OF OBESITY Excess adipose tissue cannot be directly measured in the clinical setting The best way to classify obesity in adults is the Body Mass Index (BMI) weight (kg) BMI = 2 height (m) MEASUREMENT OF OBESITY Abdominal obesity Waist circumference should be measured to evaluate patient s adiposity risk downloaded from 3

4 CLASSIFICATION OF INCREASED ADIPOSITY AND HEALTH RISK Classification BMI Waist BMI (kg/m 2 ) Comorbidity Risk Waist Circumference and Comorbidity Risk Men 40in (102cm) Women 35in (88cm) Men > 40in (102cm) Women >35in (88cm) Underweight <18.5 Low but other problems Normal weight Average Overweight Increased Increased High Obese Class I Moderate High Very High Obese Class II Severe Very High Very High Obese Class III 40 Very Severe Extremely High Extremely High OBESITY IS A CHRONIC DISEASE...the full force of our medical knowledge should be brought to bear on the prevention and treatment of obesity as a primary disease entity. It is the official position of The Obesity Society that obesity should be declared a disease. Recognizing obesity as a disease will help change the way the medical community tackles this complex issue that affects approximately one in three Americans. FDA agrees with these comments that obesity is a disease Being overweight, i.e., being more than one's ideal weight but less than obese, however, is not a disease. Obesity is a chronic disease, prevalent in both developed and developing countries, and affecting children as well as adults. downloaded from 4

5 PREVALENCE OF CHRONIC DISEASES Obesity: ~1 in 3 HTN: ~1 in 3 High Cholesterol: ~1 in 10 Diabetes: ~1 in 11 MEDICAL DIAGNOSIS OF OBESITY Anthropometric Component Candidate for Therapy? Clinical Component Patient presents with BMI 25 kg/m 2 Evaluate for overweight or obesity... Evaluate for weightrelated complications... Prediabetes Type 2 diabetes Dyslipidemia Hypertension Cardiovascular disease Nonalcoholic fatty liver disease PCOS Female infertility Male hypogonadism Obstructive sleep apnea Asthma/reactive airway disease Osteoarthritis Urinary stress incontinence GERD Depression downloaded from 5

6 LIFESTYLE THERAPY Should be available to all patients being treated for obesity MEAL PLAN Reduced calorie healthy meal plan 500 kcal daily deficit Low fat diet is an option Eat breakfast Maintain a consistent eating pattern PHYSICAL ACTIVITY Voluntary aerobic physical activity progressing to >150 minutes/week performed on 3 5 separate days per week Engage in moderate high intensity exercise at least 1 hour/day Resistance exercise 2 3x/week Reduce sedentary behavior *:Factors Associated with Successful Weight Loss Maintenance LIFESTYLE THERAPY Should be available to all patients being treated for obesity BEHAVIOR INTERVENTIONS Self monitoring (food intake, exercise, weight) Goal setting Realistic goal weight Education Problem solving strategies Stimulus control Psychological evaluation, counseling, and treatment when needed Cognitive restructuring Motivational interviewing Mobilization of social support structures Behavioral contracting Stress reduction *:Factors Associated with Successful Weight Loss Maintenance downloaded from 6

7 PHARMACOTHERAPY Is only approved as an adjunct to lifestyle therapy Not for use alone Chronic weight management of adults with an initial BMI of: kg/m 2 or greater (obese) or kg/m 2 or greater (overweight) in the presence of at least one weight related comorbidity such as hypertension, type 2 diabetes mellitus, or dyslipidemia Efficacy: pharmacotherapy + lifestyle therapy > lifestyle therapy Pharmacotherapy should be offered to patients for the chronic treatment of obesity Short term treatment (3 6 months) has not been shown to produce long term health benefits BARIATRIC SURGERY Bariatric surgical procedures cause weight loss by restricting the amount of food the stomach can hold, causing malabsorption of nutrients, or by a combination of both Gastric banding Sleeve gastrectomy Biliopancreatic Diversion with or without Duodenal Switch (Roux en Y) Gastric Bypass Vertical banded gastroplasty Indications for surgery 1. BMI 40 kg/m 2, or more than 100 pounds overweight 2. BMI 35 kg/m 2 with at least one weight related comorbidity downloaded from 7

8 TREATMENT GOALS Overweight BMI 25 No weight related complications Obese BMI 30 No weight related complications Overweight or Obese Weight related complications Prevent progressive weight gain or weight loss 1. Prevent progression to obesity 2. Prevent development of weight related complications Weight loss or prevent progressive weight gain 1. Prevent development of weight related complications 5 15% weight loss Improve weightrelated clinical outcomes MEDICATIONS FOR WEIGHT MANAGEMENT downloaded from 8

9 PHENTERMINE Approved in 1959 A central acting sympathomimetic No long term ( 1year) randomized controlled trials of phentermine have been reported Remains the most widely prescribed antiobesity drug in the U.S. PHASES OF OBESITY TREATMENT Phase 1 (Weight Loss) Phase 2 (Weight Loss Maintenance) Weight When you stop treatment, the disease comes back! 3 6 Months Indefinitely downloaded from 9

10 Orlistat (XENICAL, ALLI) Mechanism: A reversible inhibitor of gastric and pancreatic lipases, thus inhibiting absorption of dietary fats by 30% Available in a prescription product (Xenical) as well as OTC (Alli) Dosing: 120mg three times daily with each main meal containing fat (Rx) 60mg three times daily with each main meal containing fat (OTC) Cost: ~$19/day (Rx) ~$1.50/day (OTC) FDA Approval: April 1999 ORLISTAT EFFICACY Placebo Orlistat 60mg TID Orlistat 120mg TID Patients Age (years) Gender (% female) Baseline weight (kg) Baseline BMI Weight loss (%) Completers Weight loss (%) ITT % Weight Loss (in %) ITT % Weight Loss (in %) ITT side effects placebo weight loss downloaded from 10

11 ORLISTAT SAFETY Withdrawal Total (%) Withdrawal Adverse events (%) Placebo Orlistat 60mg TID Orlistat 120mg TID Pregnancy Category: X Most Common Side Effects: Fecal urgency Oily spotting Fatty/oil stool Flatus with discharge Oil evacuation Increased defecation Fecal incontinence ORLISTAT CONSIDERATIONS Efficacy has been demonstrated in RCTs up to 4 years duration Recommend a MVI with Vitamins A, D, E, K, and beta carotene at least 2 hours before or after the administration of orlistat or at bedtime Dosing adjustment with concomitant therapy: Cyclosporine: Administer cyclosporine 3 hours after orlistat Levothyroxine: Administer levothyroxine and orlistat at least 4 hours apart and monitor for changes in thyroid function GI side effects of orlistat can be managed with concomitant use of psyllium Doses should be taken with a meal containing about 15g of fat Omit dose if a meal is missed or contains no fat downloaded from 11

12 Lorcaserin (BELVIQ) Mechanism: a selective 5 HT 2c receptor agonist increased satiety and decreased food intake Available as immediate release as well as extended release (XR) tablet Dosing: Immediate release: 10mg BID (maximum 20mg/day) Extended release: 20mg daily (maximum 20mg/day) Cost: ~$8/day FDA Approval: June 2012 Controlled Substance: C IV LORCASERIN EFFICACY Placebo Lorcaserin 10mg BID Patients Age (years) Gender (% female) Baseline weight (kg) Baseline BMI Weight loss (%) Completers Weight loss (%) ITT % Weight Loss (in %) ITT % Weight Loss (in %) ITT downloaded from 12

13 LORCASERIN SAFETY Withdrawal Total (%) Withdrawal Adverse events (%) Placebo Lorcaserin 10mg BID Pregnancy Category: X Most Common Side Effects: Headache Upper respiratory infection Nausea Dizziness Fatigue Dry mouth Hypoglycemia (in diabetic patients) LORCASERIN CONSIDERATIONS No dose titration required Evaluate response by week 12; if patient has not lost 5% of baseline body weight, discontinue therapy Drug interactions with serotonergic agents: Selective serotonin reuptake inhibitors (SSRIs) Selective norepinephrine reuptake inhibitors (SNRIs) Tricyclic antidepressants (TCAs) MAOIs Serotonin receptor agonists (triptans) Dopamine agonists Valvular Heart Disease Fenfluramine removed from the U.S. market (nonspecific 5 HT 2B agonist) Nonsignificant increase in incidence of regurgitant cardiac valve disease has been observed with lorcaserin in clinical trials Lorcaserin XR Approved based on bioequivalence and bioavailability data; no clinical outcomes evaluation downloaded from 13

14 Phentermine/Topiramate ER (QSYMIA) Mechanism: Phentermine (sympathomimentic amine): release of norepinephrine in CNS hypothalamus reduced appetite Topiramate: mechanism unknown appetite suppression and satiety enhancement Available as an extended release capsule Dosing: Phentermine 7.5mg/topiramate ER 46mg once daily in the morning (recommended dose) Phentermine 15mg/topiramate ER 96mg once daily in the morning (maximum dose) Cost: ~$7/day (Rx) FDA Approval: July 2012 Controlled Substance: C IV PHENTERMINE/TOPIRAMATE ER EFFICACY Placebo phentermine 7.5mg /topiramate ER 46mg phentermine 15mg /topiramate ER 96mg Patients Age (years) Gender (% female) Baseline weight (kg) Baseline BMI Weight loss (%) Completers Weight loss (%) ITT % Weight Loss (in %) ITT % Weight Loss (in %) ITT downloaded from 14

15 PHENTERMINE/TOPIRAMATE ER SAFETY Withdrawal Total (%) Withdrawal Adverse events (%) Placebo phentermine 7.5mg /topiramate ER 46mg phentermine 15mg /topiramate ER 96mg Pregnancy Category: X REMS Program Increased risk of congenital malformations in infants exposed to phentermine/topiramate ER during the first trimester of pregnancy The importance of pregnancy prevention for females of reproductive potential The need to discontinue phentermine/topiramate ER immediately if pregnancy occurs Most Common Side Effects: Insomnia Dry mouth Constipation Dizziness Anxiety Irritability Parasthesia Dysgeusia Disturbance in attention PHENTERMINE/TOPIRAMATE ER CONSIDERATIONS Dose titration Phentermine 3.75mg/topiramate ER 23mg once daily in the morning x 14 days Phentermine 7.5mg/topiramate ER 46mg once daily in the morning (recommended dose) Evaluate response by week 12; if patient has not lost 3% of baseline body weight, discontinue therapy or escalate the dose Phentermine 11.25mg/topiramate ER 69mg once daily in the morning x 14 days Phentermine 15mg/topiramate ER 92mg once daily in the morning (maximum dose) Evaluate response after additional 12 weeks; if patient has not lost 5% of baseline body weight, discontinue therapy Contraindications: hyperthyroidism, glaucoma, MAOI administration Discontinuation requires tapering over at least 1 week Ensure adequate fluid intake Phentermine/topiramate ER phentermine + topiramate downloaded from 15

16 Naltrexone ER/Bupropion ER (CONTRAVE) Mechanism: Naltrexone (pure opioid antagonist): block opioid mediated mesolimbic dopamine autoinhibition reward center Bupropion (weak dopamine/norepinephrine inhibitor): stimulate hypothalamus appetite regulatory center Available as an extended release tablet Dosing: Usual dosage: two tablets (naltrexone 16mg/bupropion 180mg) BID Maximum dose: naltrexone 32mg/bupropion 360mg/day Cost: ~$7/day FDA Approval: September 2014 NALTREXONE ER/BUPROPION ER EFFICACY Placebo Naltrexone ER 16mg / bupropion ER 180mg BID Patients Age (years) Gender (% female) Baseline weight (kg) Baseline BMI Weight loss (%) Completers Weight loss (%) ITT % Weight Loss (in %) ITT % Weight Loss (in %) ITT 7 25 downloaded from 16

17 NALTREXONE ER/BUPROPION ER SAFETY Withdrawal Total (%) Withdrawal Adverse events (%) Placebo Naltrexone ER 16mg / bupropion ER 180mg BID Pregnancy Category: X Most Common Side Effects: Nausea Vomiting Dizziness Headache Constipation Insomnia Dry mouth Hot flush NALTREXONE ER/BUPROPION ER CONSIDERATIONS 4 week titration required Nausea related to naltrexone Evaluate response by week 12; if patient has not lost 5% of baseline body weight, discontinue therapy Contains bupropion Contraindicated in seizure disorder of a history of seizures Carries black box warning for suicidality in children, adolescents, and young adults (antidepressant drug) Avoid taking with high fat meals downloaded from 17

18 Liraglutide (SAXENDA) Mechanism: a long acting analog of human glucagon like peptide 1 (GLP 1) reduced appetite and energy intake Available as pen injector Dosing: 3mg SQ daily Cost: ~$9/day FDA Approval: December 2014 LIRAGLUTIDE EFFICACY Placebo Liraglutide 3mg SQ Patients Age (years) Gender (% female) Baseline weight (kg) Baseline BMI Weight loss (%) Completers Weight loss (%) ITT % Weight Loss (in %) ITT % Weight Loss (in %) ITT downloaded from 18

19 LIRAGLUTIDE SAFETY Withdrawal Total (%) Withdrawal Adverse events (%) Placebo Liraglutide 3mg SQ Pregnancy Category: X Most Common Side Effects: Nausea Diarrhea Vomiting Constipation LIRAGLUTIDE CONSIDERATIONS Dose titration: Start with 0.6mg SQ once daily. Increase the daily dose by 0.6mg each week to a target dose of 3mg SQ once daily Minimum of 5 weeks Evaluate response by week 16; if patient has not lost 4% of baseline body weight, discontinue therapy REMS Program: Potential risk of medullary thyroid carcinoma associated with liraglutide Risk of acute pancreatitis (including necrotizing pancreatitis) associated with liraglutide In a 3 year follow up study, obese patients with prediabetes who received continuous treatment with liraglutide 3mg SQ once daily: Had a lower incidence of diabetes diagnosis Had a significant delay in mean time to diabetes diagnosis downloaded from 19

20 CHRONIC KIDNEY DISEASE With appropriate caution, all medications for chronic weight management can be used in mild renal impairment (CrCl > 50mL/min) Some medications for chronic weight management require dose adjustments for use in moderate renal impairment (CrCl 30 49mL/min): Maximum dose: Naltrexone ER 8mg/bupropion ER 90mg BID Maximum dose: Phentermine 7.5mg/topiramate ER 46mg once daily Liraglutide, lorcaserin, and orlistat can be used at usual doses with appropriate caution Some medications for chronic weight management should be avoided for use in severe renal impairment (CrCl < 30 ml/min): Avoid naltrexone ER/bupropion ER Avoid lorcaserin Avoid phentermine/topiramate ER Liraglutide and orlistat can be used at usual doses with appropriate caution HYPERTENSION Patients with obesity are prone to BP elevation and HTN In patients with preexisting HTN, liraglutide, lorcaserin, orlistat, and phentermine/topiramate ER are preferred medications for chronic weight management Monitor HR closely in patients treated with liraglutide or phentermine/topiramate ER increases of 2 4 bpm seen Avoid naltrexone ER/bupropion ER if possible Weight loss assisted by naltrexone ER/bupropion ER in clinical trials did not lower BP Naltrexone ER/bupropion ER is contraindicated in patients with uncontrolled hypertension (>160/100) 1 st line therapy for BP control in patients with obesity: ACE I or ARB Avoid beta blockers and alpha blockers for HTN treatment, if possible downloaded from 20

21 DEPRESSION Obesity and depression are common comorbidities Based on study data, orlistat and liraglutide 3mg have the safest profile for use in patients with depression Safety trials of lorcaserin, naltrexone ER/bupropion ER, phentermine/topiramate ER have included assessment of depression, depressive symptoms, and suicidality (PHQ 9, BDI II, IDS SR, etc.) High dose phentermine/topiramate ER (15mg/92mg) was associated with an increased incidence of depression Clinical trials included patients with depression ± antidepressant medications Low dose phentermine/topiramate ER (7.5mg/46mg) may be considered in patients with obesity and depression Caution is warranted with lorcaserin Clinical trials excluded patients taking antidepressants Risk of euphoria and dissociative events Caution is warranted with naltrexone ER/bupropion ER Clinical trials excluded patients with serious psychiatric illness NOT approved as an antidepressant SUBSTANCE USE Opioids No issues or drug interactions with opioid medications and lorcaserin, liraglutide 3mg, orlistat, and phentermine/topirmate ER Naltrexone ER/bupropion ER: naltrexone (opioid receptor antagonist) Antagonizes effects of opioids used for cough suppression (e.g., codeine), treatment of diarrhea, and analgesia (e.g., hydrocodone) Contraindicated in patients treated with chronic opioids or during acute opioid withdrawal Patients requiring chronic opioids avoid naltrexone ER/bupropion ER Patients requiring short term opioids temporarily discontinue naltrexone ER/bupropion ER An opioid free interval of 7 10 days is recommended to avoid withdrawal symptoms Alcohol Avoid for patients taking phentermine/topiramate ER Naltrexone ER/bupropion ER should be avoided in patients with alcohol abuse; contraindicated during alcohol withdrawal downloaded from 21

22 NATURAL MEDICINES AND SUPPLEMENTS FOR WEIGHT LOSS NATURAL MEDICINES AND SUPPLEMENTS EPHEDRA (MA HUANG) Thermogenic agent Ephedra plant naturally contains ephedrine, pseudoephedrine, and phenylpropanolamine Formerly the most common ingredient in many popular herbal products (Metabolife, GlycoLEAN, Accelerator 2, Thermo Sculpt, etc.) 2004: The FDA banned ephedra products in the U.S. due to safety concerns (heart attack, arrhythmia, stroke, psychosis, seizures, and death) 2005: The dietary supplement industry was successful in challenging the ban 2006: The ban was reinstated following appeal by the FDA BITTER ORANGE Thermogenic agent Active ingredient: synephrine Most products containing bitter orange provide 10 40mg synephrine per dose Often advertised as the ephedra alternative or ephedra free Case reports of stroke and CV events (arrhythmias, heart attack, angina) and death Bitter orange + caffeine can cause QT prolongation Possibly unsafe; insufficient evidence of efficacy downloaded from 22

23 NATURAL MEDICINES AND SUPPLEMENTS HOODIA Appetite suppressant No reliable evidence supporting use for weight loss Use has been associated with cardiovascular toxicity (increased BP and HR) and liver toxicity (increased bilirubin and ALP) Insufficient evidence of efficacy or safety CONJUGATED LINOLEIC ACID (CLA) Saturated fat found primarily in dairy products and beef Reported to decrease body fat mass and potentially increase lean body mass; has not been shown to reduce total body weight or BMI Concerns for long term safety related to fatty liver and insulin resistance GARCINIA CAMBOGIA Fruit and rind extracts The majority of evidence finds that taking garcinia does not increase satiety and produces no or minimal weight loss in obese patients No reports of serious side effects, but some reports of mild digestive problems Possibly safe; possibly ineffective GREEN COFFEE EXTRACT Coffee beans that have not yet been roasted (contain higher concentration of chlorogenic acid) Some trials have evaluated specific forms of green tea extract Results show weight loss up to ~2.5kg after 6 weeks Possibly safe; insufficient evidence of efficacy Possibly safe; possibly effective NATURAL MEDICINES AND SUPPLEMENTS CALCIUM Recently, growing evidence of a role of calcium in weight loss Increasing calcium consumption to mg/day (recommended daily servings) Increased weight loss, up to 8 9 kg Increased lean body mass Body fat loss Benefits are independent of calcium supplements alone Recommend increased intake of low fat dietary sources first; supplements can be used if needed SUMMARY For natural medicines and supplements, clinicians should help patients sort through the marketing noise Evaluate products for efficacy and safety Natural Medicines Database is available through Lewis Library Advise patients to use products with proprietary blends (e.g.,hydroxycut) with caution downloaded from 23

24 KEY POINTS OBESITY Once established obesity becomes a chronic, often progressive disease Assess patients and document obesity properly Measure height, weight, and BMI at least annually Utilize structured lifestyle interventions Recommend reducing calorie intake Recommend increasing physical activity Employ behavior therapy Treat patients with medications for chronic weight management as appropriate Avoid medications that cause weight gain, if possible Refer patients to and support those who have had bariatric surgery Help patients keep track of information to meet their goals KEY POINTS PHARMACOTHERAPY Current medications for management of overweight and obesity require long term treatment All medications are to be used as adjunct to lifestyle interventions Not necessary to consider medications a rescue strategy Each obesity drug has been shown to be more effective than placebo in achieving weight loss at 1 year Long term treatment with drug therapy has benefits of sustained weight loss and control of comorbidities such as blood glucose, blood pressure, and dyslipidemia No weight loss medication has been shown to have a favorable effect on cardiovascular morbidity and mortality Choose drug therapy based on side effects, comorbid conditions, and cost Discontinue treatment if patient doesn t lose 4 5% of initial body weight after weeks of therapy It is reasonable to be cautious as medications have been studied for a limited time (1 4 years) downloaded from 24

25 REFERENCES 1. Cavaliere H, Floriano I, Medeiros Neto G. Gastrointestinal side effects of orlistat may be prevented by concomitant prescription of natural fibers (psyllium mucilloid). Int J Obes Relat Metab Disord Jul;25(7): Elfhag K, Rössner S. Who succeeds in maintaining weight loss? A conceptual review of factors associated with weight loss maintenance and weight regain. Obes Rev Feb;6(1): Fidler MC, Sanchez M, Raether B, et al; BLOSSOM Clinical Trial Group. A one year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab Oct;96(10): Gadde KM, Allison DB, Ryan DH, et al.effects of low dose, controlled release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo controlled, phase 3 trial. Lancet Apr 16;377(9774): Garvey WT, Mechanick JI, Brett EM, et al; Reviewers of the AACE/ACE ObesityClinical Practice Guidelines. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY COMPREHENSIVE CLINICAL PRACTICE GUIDELINES FOR MEDICAL CARE OF PATIENTS WITH OBESITY EXECUTIVE SUMMARY Complete Guidelines available at Endocr Pract. 2016Jul;22(7): Garvey WT, Mechanick JI, Brett EM, et al; Reviewers of the AACE/ACE ObesityClinical Practice Guidelines. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY COMPREHENSIVE CLINICAL PRACTICE GUIDELINES FOR MEDICAL CARE OF PATIENTS WITH OBESITY. Endocr Pract Jul;22 Suppl 3: Garvey WT, Garber AJ, Mechanick JI, et al; The Aace Obesity Scientific Committee. American association of clinical endocrinologists and american college of endocrinology position statement on the 2014 advanced framework for a new diagnosis of obesity as a chronic disease. Endocr Pract Sep;20(9): Greenway FL, Fujioka K, Plodkowski RA, et al; COR I Study Group. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR I): a multicentre, randomised, double blind, placebo controlled, phase 3 trial. Lancet Aug 21;376(9741): Hauptman J, Lucas C, Boldrin MN, et al. Orlistat in the long term treatment of obesity in primary care settings. Arch Fam Med Feb;9(2): REFERENCES 10. Jensen MD, Ryan DH, Apovian CM, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; Obesity Society 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 Guidelines and The Obesity Society. J Am Coll Cardiol Jul 1;63(25 Pt B): Khera R, Murad MH, Chandar AK, et al. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta analysis. JAMA Jun 14;315(22): le Roux CW, Astrup A, Fujioka K, et al; SCALE Obesity Prediabetes NN Study Group. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double blind trial. Lancet Apr 8;389(10077): Natural Medicines in the Clinical Management of Obesity and Weight Loss. Pharmacist's Letter Published Accessed August 29, Pi Sunyer X, Astrup A, Fujioka K, et al; SCALE Obesity and Prediabetes NN Study Group. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med Jul 2;373(1): PL Detail Document, Weight Loss: Helping Your Overweight and Obese Patients. Pharmacist s Letter/Prescriber s Letter. May PL Clinical Resource, Drugs for Weight Loss. Pharmacist s Letter/Prescriber s Letter. January Wing RR, Phelan S. Long term weight loss maintenance. Am J Clin Nutr Jul;82(1 Suppl):222S 225S. 18. Yanovski SZ, Yanovski JA. Long term drug treatment for obesity: a systematicand clinical review. JAMA Jan 1;311(1): downloaded from 25