Clinical Issues in Type 2 Diabetes

Held in conjunction with the American Diabetes Association’s 76th Scientific Sessions

This activity is jointly provided by Global Education Group and Integritas Communications.

This activity is supported by an educational grant from AstraZeneca.

CME/MEDICAL COMMUNICATIONS INQUIRIES info@integritasgrp.com integritasgrp.com

FACULTY FACULTY

JOHN E. Anderson, MD Internist Past President, The Frist Clinic Nashville, Tennessee

Dr. John E. Anderson received his medical degree from the University of Virginia School of Medicine in Charlottesville, Virginia, and completed his residency at Vanderbilt University in Nashville, Tennessee. He practices internal medicine and diabetes at the Frist Clinic, a multispecialty Internal Medicine group in Nashville, Tennessee, and is a Past President of the group. He has also been Chair of the Department of Medicine and Chair of the Board of Trustees of Centennial Medical Center, a 770-bed tertiary care referral hospital also in Nashville.

Dr. Anderson has been a longtime volunteer for the American Diabetes Association, serving two separate terms on its Board of Directors and chairing the National Advocacy Committee. In 2013 he was President of Medicine and Science for the Association.

Dr. Anderson has lectured both nationally and internationally on topics of diabetes, with a focus on improving the knowledge and care of people with diabetes in the primary care community.

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ALAN J. Garber, MD, PhD, FACE FACULTY

Professor Medicine, Biochemistry, and Molecular and Cellular Biology Diabetes, Endocrinology and Metabolism Baylor College of Medicine Houston, Texas

Dr. Alan J. Garber graduated from Temple University, Philadelphia, in 1968, and completed a PhD in Physiological Chemistry in 1971 and a residency in Internal Medicine. Subsequently, he was a fellow in Metabolism and a junior faculty member at Washington University Medical School and Barnes Hospital in St. Louis, Missouri. In 1974, he transferred to Baylor College of Medicine in Houston, where he is presently a Professor in the Departments of Medicine, Biochemistry and Molecular Biology, and Molecular and Cellular Biology.

Dr. Garber is president of the American College of Endocrinology and a past president of the American Association of Clinical Endocrinologists. Prior service to the boards of numerous organizations includes the National Board of Directors of the American Association of Clinical Endocrinologists, the American Diabetes Association, the Southern Section of the American Federation for Clinical Research, and the Southern Society for Clinical Investigation. Prior elected positions include those of secretary/ treasurer and president, American Association of Clinical Endocrinologists; Board of Chancellors, the American College of Endocrinology; president, the Southern Society for Clinical Research; president, the Southern Society for Clinical Investigation; and president, the American Diabetes Association Texas Affiliate.

Consulting positions include the National Institutes of Health (NIH), the National Heart, Lung, and Blood Institute, the American Heart Association, and the National Kidney Foundation. Dr. Garber has served as the editor of Clinical Diabetes, Endocrine and Metabolism Clinics of North America, and Medical Clinics of North America, and is presently the editor of Diabetes, Obesity and Metabolism, and Endocrine Today.

Additionally, Dr. Garber is a member of the National Lipid Association and a past-member of the NIH-Food and Drug Administration (FDA) Expert Panel on Cardiovascular Biomarkers, AACE liaison to the FDA and the American College of Cardiology, and past-chair of the Council on Complications for the American Diabetes Association. He has authored over 300 peer-reviewed publications, as well as book chapters and monographs on diabetes, its complications, and related disorders.

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JULIO Rosenstock, MD FACULTY

Director, Dallas Diabetes and Endocrine Center Clinical Professor of Medicine University of Texas Southwestern Medical Center Dallas, Texas

Dr. Julio Rosenstock is Director of the Dallas Diabetes and Endocrine Center at Medical City, an endocrine practice and clinical research facility, and Clinical Professor of Medicine at the University of Texas Southwestern Medical Center.

He received his medical degree from the University of Costa Rica School of Medicine.

He completed fellowships in Endocrinology and Diabetes at the Royal Postgraduate Medical School, Hammersmith Hospital in London and at the University of Texas Southwestern Medical Center in Dallas. He is board certified in Internal Medicine and in Endocrinology and Metabolism.

His clinical and research activities have focused on exploring novel agents and therapeutic strategies to improve glycemic control acting as a clinical investigator and scientific advisor, with a particular interest in early insulin interventions with combination strategies in type 2 diabetes. He is recognized worldwide as a key opinion leader in the field of diabetes and over the last 30 years he has participated in hundreds of clinical trials for the development of new oral agents and insulin preparations.

He has authored more than 400 publications, including peer-reviewed papers and numerous abstracts, and has also contributed to several clinics and book chapters on various topics in the field of diabetes. He is currently an associate editor of Diabetes Care; an editorial board member of the journals Practical Diabetology, Cardiovascular Diabetology, and Diabetes Management; and an active reviewer for several journals.

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TARGET AUDIENCE The educational design of this activity addresses the needs of endocrinologists, internists, and other practitioners involved in the diagnosis and treatment of type 2 diabetes mellitus (T2DM).

PREAMBLE

STATEMENT of NEED/PROGRAM OVERVIEW Over the last decade, increased understanding of the pathophysiology of type 2 diabetes mellitus (T2DM) has aided the development of new and expanding classes of antihyperglycemic medications.1,2 For example, particularly promising results have been observed with agonists of glucagon-like peptide-1 (GLP-1) receptors, and inhibitors of either dipeptidyl peptidase 4 (DPP4) or sodium-glucose cotransporter 2 (SGLT2).3-6 The threshold challenge for clinicians who manage individuals with T2DM is how to best combine these agents in multimodal treatment regimens to address patients’ numerous medical, psychosocial, and educational needs. Indeed, achieving patient-centered targets for blood glucose and other clinical parameters with appropriately aggressive therapy is critical to optimize T2DM outcomes.1,7 National society guidelines stress the need for individualized care and proactive clinician and patient engagement to overcome clinical inertia, while balancing intensification of therapy against treatment-related risks, especially hypoglycemia.1,7,8 Yet debate around the practical implications of large-scale studies confound day-to-day decision-making by endocrinologists and other diabetes-focused clinicians, elevating the importance of clinical experience in managing diverse patient populations. Further complicating these issues, the evidence base is constantly evolving, and the volume of published information about T2DM can obscure the most clinically relevant data for health care practitioners. This Clinical Issues™ program will provide attendees at the 2016 Scientific Sessions of the American Diabetes Association with expert interpretations of recent clinically relevant trial data and actionable recommendations around the use of combinations of noninsulin antihyperglycemic agents in the management of T2DM.

REFERENCES 1. American Diabetes Association. Diabetes Care. 2015;39(suppl 1):S1-S112.

2. Defronzo RA. Diabetes. 2009;58(4):773-795.

3. Mogensen UM, et al. Diabetes Obes Metab. 2014;16(10):1001-1008.

4. Eng C, et al. Lancet. 2014;384(9961):2228-2234.

5. Wu JH, et al. Lancet Diabetes Endocrinol. 2016:4(5):411-419.

6. Liu XY, et al. J Diabetes Complications. 2015;29(8):1295-1303.

7. Garber AJ, et al. Endocr Pract. 2016;22(1):84-113.

8. Seaquist ER, et al. J Clin Endocrinol Metab. 2013;98(5):1845-1859.

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EDUCATIONAL OBJECTIVES After completing this activity, the participant should be better able to: • Identify patient-specific treatment goals in T2DM that reflect disease severity, comorbidities, therapeutic risks, and psychosocial status • Discuss the profiles, evidence for clinical benefits, and associated warnings for noninsulin antihyperglycemic medications

• Utilize motivational interviewing techniques to engage patients in their antidiabetes management plans, facilitate lifestyle changes, and improve treatment adherence

PHYSICIAN ACCREDITATION STATEMENT This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Global Education Group (Global) and Integritas. Global is accredited by the ACCME to provide continuing medical education for physicians.

This CME/CE activity complies with all requirements of the federal Physician Payment Sunshine Act. If a reportable event is associated with this activity, the accredited provider managing the program will provide the appropriate physician data to the Open Payments database.

PHYSICIAN CREDIT DESIGNATION Global Education Group designates this live activity for a maximum of 2.0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

GLOBAL CONTACT INFORMATION For information about the accreditation of this program, please contact Global at (303) 395-1782 or inquire@globaleducationgroup.com.

INSTRUCTIONS TO RECEIVE CREDIT In order to receive credit for this activity, the participant must complete the program evaluation.

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PREAMBLE

• Intensify multidrug noninsulin regimens for various patient types to optimize glycemic control and improve other clinical parameters

FEE INFORMATION & REFUND/ CANCELLATION POLICY There is no fee for this educational activity.

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DISCLOSURE OF CONFLICTS OF INTEREST Global Education Group (Global) requires instructors, planners, managers, and other individuals and their spouses/life partners who are in a position to control the content of this activity to disclose any real or apparent conflict of interest they may have as related to the content of this activity. All identified conflicts of interest are thoroughly vetted by Global for fair balance, scientific objectivity of studies mentioned in the materials or used as the basis for content, and appropriateness of patient care recommendations.

The faculty have reported the following financial relationships or relationships to products or devices they or their spouses/life partners have with commercial interests related to the content of this CME activity.

John E. Anderson, MD Consultant – Abbott Diabetes Care, Inc., AstraZeneca plc, Boehringer Ingelheim GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., sanofi-aventis U.S. LLC. Honoraria – Abbott Diabetes Care, Inc., AstraZeneca plc, Boehringer Ingelheim GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., sanofi-aventis U.S. LLC. Speakers Bureaus – Abbott Diabetes Care, Inc., AstraZeneca plc, Boehringer Ingelheim GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., sanofiaventis U.S. LLC. Alan J. Garber, MD, PhD Consultant – Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S Julio Rosenstock, MD Consultant –AstraZeneca plc, Boehringer Ingelheim GmbH, Daiichi Sankyo Company, Limited, GlaxoSmithKline, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., F. Hoffmann-La Roche Ltd, sanofi-aventis U.S. LLC., Takeda Pharmaceutical Company Limited; Grant/ Research Support – AstraZeneca plc, Boehringer Ingelheim GmbH, Bristol-Myers Squibb, Daiichi Sankyo Company, Limited, Eli Lilly and Company, GlaxoSmithKline, Intarcia Therapeutics, Inc., Janssen

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Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc., F. Hoffmann-La Roche Ltd, sanofi-aventis U.S. LLC., Takeda Pharmaceutical Company Limited; Honoraria – AstraZeneca plc, Boehringer Ingelheim GmbH, Daiichi Sankyo Company, Limited, GlaxoSmithKline, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., F. Hoffmann-La Roche Ltd, sanofi-aventis U.S. LLC., Takeda Pharmaceutical Company Limited

Amanda Glazar, PhD

Nothing to disclose

Andrea Funk

Nothing to disclose

Jim Kappler, PhD

Nothing to disclose

PREAMBLE

The planners and managers have reported the following financial relationships or relationships to products or devices they or their spouses/life partners have with commercial interests related to the content of this CME activity.

DISCLOSURE OF UNLABELED USE This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. Global and Integritas Communications do not recommend the use of any agent outside of the labeled indications.

The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of any organization associated with this activity.

Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

DISCLAIMER Participants have an implied responsibility to use newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management.

Any procedures, medications, or other courses of diagnosis or treatment discussed in this activity should not be used by clinicians without evaluation of patient conditions, possible contraindications, dangers of use, review of applicable manufacturer’s product information, and comparison with recommendations of other authorities.

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GUIDELINES »» Standards of Medical Care in Diabetes—2016.

The ADA’s Standards of Care provide clinicians, patients, researchers, payers, and other interested individuals with the components of good diabetes management, general treatment goals, and tools to evaluate the quality of care. Importantly, these recommendations should be adjusted based on individual preferences, comorbidities, and other patient-related factors.

American Diabetes Association. Diabetes Care. 2016;39(suppl 1):S1-S112. http://care.diabetesjournals.org/content/diacare/suppl/2015/12/21/39.

Supplement_1.DC2/2016-Standards-of-Care.pdf

»» AACE/ACE Comprehensive Diabetes Management Algorithm 2016.

The AACE/ACE algorithm provides recommendations on evaluating the whole patient, outlines potential risks and complications, and highlights evidence-based treatment approaches for diabetes. The document contains sections on lifestyle changes, considerations for obese individuals, prediabetes, glycemic goals, antihyperglycemic therapies, treatment algorithms, modifications for atherosclerotic cardiovascular disease risk factors, and overall principles of diabetes management.

Garber AJ, Abrahamson MJ, Barzilay JI, et al. Endocr Pract.

2016;22(1):84-113. https://www.aace.com/files/aace_algorithm_slides.pptx

PATIENT RESOURCES Created as part of the National Diabetes Education Program, Diabetes HealthSense includes easily accessible resources that can help patients live well and meet their goals—whether they have diabetes or are at risk for the disease. http://ndep.nih.gov/resources/diabetes-healthsense/

»» Decision Aids for T2DM To facilitate shared decision making, these examples of medication choice decision aids from the Mayo Clinic are organized into 7 issues that may be of interest to patients with T2DM. A video demonstrating the use of these cards can be found at: https://www.youtube.com/ watch?v=SYTPqceFgSw. http://shareddecisions.mayoclinic.org/files/2011/08/Diabetes-brochure.pdf

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RESOURCE CENTER

»» Diabetes HealthSense

SUGGESTED READINGS »» From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus.

Defronzo RA. Diabetes. 2009;58(4):773-795. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661582/pdf/zdb773.pdf

»» Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes.

Diamant M, Nauck MA, Shaginian R, et al. Diabetes Care. 2014;37(10):2763-2773. http://care.diabetesjournals.org/content/diacare/37/10/2763.full.pdf

»» Dapagliflozin compared with other oral anti-diabetes treatments when added to metformin monotherapy: a systematic review and network meta-analysis.

Goring S, Hawkins N, Wygant G, et al. Diabetes Obes Metab. 2014;16(5):433-442. http://onlinelibrary.wiley.com/doi/10.1111/dom.12239/pdf

»» Glycemic variability and diabetes complications: does it matter?

Of course it does!

Hirsch IB. Diabetes Care. 2015;38(8):1610-1614. http://care.diabetesjournals.org/content/38/8/1610

»» Minimizing hypoglycemia in diabetes.

International Hypoglycemia Study Group. Diabetes Care. 2015;38(8):1583-1591.

RESOURCE CENTER

http://care.diabetesjournals.org/content/38/8/1583.full.pdf+html

»» Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes.

Inzucchi SE, Bergenstal RM, Buse JB, et al. Diabetes Care. 2015;38(1):140-149. http://care.diabetesjournals.org/content/38/1/140.full.pdf+html

»» The safety of dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter 2 (SGLT-2) inhibitors added to metformin background therapy in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

Kawalec P, Mikrut A, Łopuch S. Diabetes Metab Res Rev. 2014;30(4):269-283. http://onlinelibrary.wiley.com/doi/10.1002/dmrr.2494/full

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FACULTY

»» Combination therapy for the improvement of long-term macrovascular and microvascular outcomes in type 2 diabetes: rationale and evidence for early initiation.

Milligan S. J Diabetes Complications. 2016 Mar 15 [Epub ahead of print]. http://www.jdcjournal.com/article/S1056-8727(16)30047-2/pdf

»» Early combination therapy for the treatment of type 2 diabetes mellitus: systematic review and meta-analysis.

Phung OJ, Sobieraj DM, Engel SS, Rajpathak SN. Diabetes Obes Metab. 2014;16(5):410-417. http://www.ncbi.nlm.nih.gov/pubmed/24205921

PREAMBLE

»» GLP-1 receptor agonists: practical considerations for clinical practice.

Triplitt C, Solis-Herrera C. Diabetes Educ. 2015;41(1 Suppl):32S-46S. http://tde.sagepub.com/content/41/1_suppl/32S.full.pdf+html

»» Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes.

Zinman B, Wanner C, Lachin JM, et al. N Engl J Med. 2015;373(22):2117-2128.

RESOURCE CENTER

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http://www.nejm.org/doi/pdf/10.1056/NEJMoa1504720

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Please visit the CLINICAL RESOURCE CENTER for additional information and resources

www.EXCHANGECME.com/ADA2016

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All rights reserved. No part of this syllabus may be used or reproduced in any manner whatsoever without written permission except in the case of brief quotations embedded in articles or reviews.