Clinical Management of Obesity Clinical Management of Obesity Caroline M. Apovian, MD Louis Aronne, MD Amanda G. Powell, MD Apovian , Aronne & Powell First Edition Clinical Management of Obesity First Edition Caroline M. Apovian, MD Professor of Medicine and Pediatrics, Boston University School of Medicine Director, Center for Nutrition and Weight Management, Section of Endocrinology, Diabetes, and Nutrition Boston Medical Center Louis Aronne, MD Sanford I. Weill Professor of Metabolic Research, Weill Cornell Medical College Director of the Comprehensive Weight Control Center, New York Presbyterian/Weill Cornell Medical Center Amanda G. Powell, MD Assistant Professor of Medicine Tufts University School of Medicine Director of Medical Weight Loss Lahey Hospital & Medical Center Copyright 2015 Caroline M. Apovian, MD Louis Aronne, MD Amanda G. Powell, MD Professional Communications, Inc. A Medical Publishing & Communications Company 400 Center Bay Drive 1223 W. Main St, #1427 West Islip, NY 11795 Durant, OK 74702-1427 (t) 631/661-2852 (t) 580/745-9838 (f) 631/661-2167 (f) 580/745-9837 All rights reserved. No part of this publication may be re pro duced or DEDICATION transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any other information storage and retrieval system, without the prior agreement and written permission of the publisher. To the millions of patients suffering with their weight. We hope that this book helps providers ¿ nd For orders only, please call effective tools to manage the obesity epidemic. 1-800-337-9838 or visit our Web site at www.pcibooks.com ISBN: 978-1-932610-93-2 Printed in the United States of America DISCLAIMER The opinions expressed in this publication reÀ ect those of the authors. However, the authors make no warranty regarding the con- tents of the publication. The protocols described herein are general and may not apply to a speci¿ c patient. Any product mentioned in this publication should be taken in accordance with the prescribing information provided by the manufacturer. This text is printed on recycled paper. ii iii TABLE OF CONTENTS Prevalence of Obesity and 1 Related Mortality The Pathophysiology of Obesity 2 Obesity-Related Comorbidities 3 A Complications-Centric Approach 4 to the Treatment of Obesity ACKNOWLEDGMENT Bene¿ ts of Weight Loss 5 We would like to thank Malcolm Beasley for as- Approach to the Obese Patient 6 suring us that we could achieve the unachievable by writing an entire handbook on obesity in 9 months. We 7 would like to thank Victor Runowicz for his assistance Drug-Induced Weight Gain in the preparation of the manuscript. Dietary Interventions, Physical Activity, 8 and Behavioral Approaches to the Treatment of Obesity Pharmacologic Treatment 9 Bariatric Surgery 10 Abbreviations/Acronyms 11 Index 12 iv v TABLES Table 9.1 Obesity Medications Available Prior to 2012 .....184 Table 9.2 Summaries of Prescribing Information for Table 1.1 Cause-Speci¿ c Mortality vs BMI in the Currently Available Obesity Medications ...........186 Ranges of 15-25 kg/m2 and 25-50 kg/m2 ..............18 Table 9.3 Summary of Primary Ef¿ cacy Endpoints Table 3.1 Associations Between Biomarker Levels From Three Randomized, Placebo-Controlled and Obesity Class: NHANES 1999-2004 .............49 Trials of Combination Treatment With Table 3.2 CRP and Fibrinogen Levels According Phentermine/Topiramate ER in to Diabetes and Hypertension Status .....................51 Overweight/Obese Patients .................................200 Table 3.3 Prevalence and Adjusted Odds Ratios of Table 9.4 Summary of Mean Changes From Baseline Comorbidities According to Body Weight ............55 in Metabolic and CV Risk Factors and Waist Circumference in Randomized, Table 3.4 Impact of BMI Category on Increasing Placebo-Controlled Trials With Fixed-Dose Number of Concurrent Comorbidities ..................57 Combination Treatment With Phentermine/ Table 4.1 Edmonton Obesity Staging System (EOSS) .........81 Topiramate ER in Overweight/Obese Patients ....206 Table 4.2 Risk Factors of Metabolic Syndrome ....................85 Table 9.5 Summary of Adverse Events With Incidence 1% Leading to Treatment Discontinuation Table 4.3 Cardiometabolic Disease Staging System in the EQUIP and CONQUER Clinical Trials ....209 (CMDS) .................................................................88 Table 9.6 Summary of Primary Ef¿ cacy Endpoints From Table 4.4 BMI-Centric Guide to Choosing Treatments Three Randomized, Placebo-Controlled Trials for Obesity .............................................................92 of Lorcaserin in Overweight/Obese Patients .......214 Table 5.1 Incidence (Cases per 100 Person-Years) of Table 9.7 Mean Changes From Baseline in Metabolic and Diabetes During DPP, Bridge Period, and CV Risk Factors in Randomized, Placebo- DPPOS ..................................................................99 Controlled Trials With Lorcaserin in Table 5.2 Risk Factors of Metabolic Syndrome ..................104 Overweight/Obese Patients .................................220 Table 5.3 Look AHEAD Study: Mean Changes in Table 9.8 Summary of Adverse Events Reported by Weight, Fitness, and CVD Risk Factors in 2% of Lorcaserin Patients and More ILI and DSE Groups and the Difference Commonly Than With Placebo in Patients Between Groups Averaged Across 4 Years .........107 Without Diabetes in the BLOSSOM, BLOOM, and BLOOM-DM Studies ...................222 Table 6.1 Classes of Medications Promoting Weight Gain .........................................................130 Table 9.9 Summary of Primary Ef¿ cacy Endpoints From Three Randomized, Placebo-Controlled Trials Table 6.2 BMI .....................................................................132 of Combination Treatment With Naltrexone ER/ Table 6.3 Variations in Percentage of Body Fat for Bupropion ER in Overweight/Obese Patients .....226 Blacks, Asians, and Whites .................................134 Table 9.10 Summary of Mean Changes From Baseline in Table 7.1 List of Select Drugs That Are Weight Metabolic and CV Risk Factors and Waist Gaining, Weight Neutral, and Weight Circumference in 56-Week Randomized, Reducing for Each Type of Treatment ................148 Placebo-Controlled Trials With Fixed-Dose Combination Treatment With Naltrexone SR/ Table 8.1 Sample Dietary Compositions .............................163 Bupropion SR ......................................................234 Table 8.2 Comparison of Lifestyle Intervention Table 9.11 Adverse Reactions Wth an Incidence of at Features of Diabetes Prevention Program Least 2% Among Patients Treated With and Look AHEAD Trial ......................................174 Naltrexone SR/Bupropion SR and More Commonly Than Placebo ....................................236 vi vii Table 9.12 Changes From Randomization to Week 56 in Figure 2.2 Peptide Modulators of Food Intake and Measures of Glycemic Control, Lipids, and Energy Expenditure ...............................................27 Cardiovascular Biomarkers .................................240 Figure 2.3 Brain Sensing of Gut- and Adipocyte-Derived Table 9.13 Adverse Reactions With an Incidence of at Hormones ..............................................................29 Least 2% Among Patients Treated With Figure 2.4 CNS Regulates Food Intake, Energy Expenditure, Liraglutide and More Commonly Than and Reward in Response to Satiety Signals ..........32 Placebo ................................................................244 Figure 2.5 Naltrexone Potentiates the Actions of Table 10.1 RYGB: Potential Advantages and Bupropion ..............................................................34 Disadvantages .....................................................256 Figure 2.6 Actions of Lorcaserin Enhance POMC .................35 Table 10.2 VSG: Potential Advantages and Disadvantages .....................................................258 Figure 3.1 Comorbidities Associated With Obesity ...............48 Table 10.3 BPD/DS: Potential Advantages and Figure 3.2 Factors Secreted by Adipose Tissue ......................49 Disadvantages .....................................................260 Figure 3.3 Relationships Between Body Weight and Table 10.4 AGB: Potential Advantages and Diabetes .................................................................52 Disadvantages .....................................................263 Figure 4.1 Complications-Centric Model for Care of Table 10.5 Pooled Data From Systematic Review ................266 the Overweight/Obese Patient ...............................76 Table 10.6 Estimated Rates (%) of Surgical Risks and Figure 4.2 Prediction of All-Cause Mortality Using Complications .....................................................270 EOSS or BMI Criteria ...........................................82 Table 10.7 Short-Term and Long-Term Weight Loss Figure 4.3 Cumulative Diabetes Incidence as a Function With RYGB, AGB, or VSG .................................274 of Increasing CMDS Risk Stage: CARDIA Study Cohort .........................................................90 Table 10.8 Routine Postsurgical Laboratory Follow-Up of Individuals After Bariatric Surgery .................279 Figure 4.4 Survival Probability as a Function of Increasing CMDS Risk Stage: NHANES .............91 FIGURES Figure 4.5 Intensi¿ cation of Therapies to Achieve Weight Loss Goals ................................................93 Figure 1.1 Trends in the Prevalence of Overweight, Figure 5.1 DPP Study: Cumulative Incidence