Multidimensional Issues in Type 2 Diabetes

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

This activity is supported by an independent educational grant from AstraZeneca.

MEDICAL COMMUNICATIONS INQUIRIES info@integritasgrp.com integritasgrp.com

FACULTY

FACULTY

Lawrence Blonde, MD, FACP, MACE Director, Ochsner Diabetes Clinical Research Unit Frank Riddick Diabetes Institute Department of Endocrinology Ochsner Medical Center New Orleans, Louisiana Dr. Lawrence Blonde is Director of the Ochsner Diabetes Clinical Research Unit, in the Frank Riddick Diabetes Institute, Department of Endocrinology, at the Ochsner Medical Center. He is also an Associate Editor for Diabetes Care.

In May 2016, he received the Master of the American College of Endocrinology (MACE) Award.

In 2011, he was a member of the Executive Committee and immediate past Chair of the Steering Committee of the National Diabetes Education Program (NDEP), a partnership of the National Institutes of Health and the Centers for Disease Control and Prevention. Dr. Blonde coauthored the 2015 American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) – Clinical Practice Guidelines for Developing a Diabetes Mellitus Comprehensive Care Plan and the 2017 AACE/ACE Comprehensive Type 2 Diabetes Management Algorithm.

Dr. Blonde has been a member of the AACE Board of Directors, the ACE Board of Trustees, and the ADA Board of Directors. He is also former chair of the ADA Professional Practice Committee, which develops practice guidelines for the care of people with diabetes.

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Serge A. Jabbour, MD, FACP, FACE FACULTY

Professor of Medicine Director, Division of Endocrinology, Diabetes and Metabolic Diseases Sidney Kimmel Medical College Thomas Jefferson University Philadelphia, Pennsylvania

Dr. Serge A. Jabbour is Professor of Medicine and Director of the Division of Endocrinology, Diabetes and Metabolic Diseases in the Department of Medicine at Sidney Kimmel Medical College of Thomas Jefferson University. He is also Director of the Jefferson Diabetes Center.

Dr. Jabbour completed his training in Endocrinology, Diabetes, and Metabolic Diseases at Thomas Jefferson University. He has received many honors and teaching awards.

Philadelphia magazine has named him one of their Top Docs™ every year since 2011, and Castle Connolly has listed him as one of the best endocrinologists in the nation every year since 2012.

A member of numerous professional organizations, including the Endocrine Society, the American Diabetes Association, and the American Association of Clinical Endocrinologists, Dr. Jabbour serves on the editorial boards of numerous journals and chairs the Endocrine Board Review Committee for the Endocrine Society. He has published many articles and chapters on diabetes, metabolic syndrome, and various endocrine topics.

Dr. Jabbour’s main research interest is diabetes. He is involved in many clinical research trials related to new diabetes drugs. He also frequently lectures all over the world on different endocrine topics, mainly diabetes, in the setting of grand rounds, symposia, or other continuing medical education presentations.

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Medical Director, AdventHealth Diabetes Institute Senior Investigator and Diabetes Program Lead, Translational Research Institute for Metabolism and Diabetes Orlando, Florida

Dr. Richard E. Pratley is Medical Director of the AdventHealth Diabetes Institute (AHDI). He is also Senior Investigator and Diabetes Program Lead at the Translational Research Institute for Metabolism and Diabetes.

Dr. Pratley has served as Head of the Diabetes and Metabolism Unit of the National Institutes of Health (NIH) Clinical Diabetes and Nutrition Section in Phoenix, Arizona. He then took a position as Senior Director in the Cardiovascular and Metabolism Therapeutic Area at Novartis Pharmaceuticals, where he worked on the clinical development of new diabetes treatments. From 2004 to 2011, Dr. Pratley was the Director of the University of Vermont’s Diabetes and Metabolism Translational Medicine Unit and a Professor at their College of Medicine. There he led many large-scale investigations, including NIH- and pharmaceutical company–sponsored studies.

As a member of the American Diabetes Association, the European Association for the Study of Diabetes, and The Obesity Society, Dr. Pratley continues his active involvement in the professional community. The American Federation for Medica Research awarded him the Henry Christian Award for Excellence in Clinical Research. Dr. Pratley regularly presents at national and international meetings, has written over 240 peer-reviewed articles, and is a Principal Investigator for both NIH- and pharmaceutical company–sponsored trials in diabetes and obesity. He is on the editorial boards of Diabetes Care, The Lancet Diabetes and Endocrinology, The Journal of Clinical Endocrinology & Metabolism, the Journal of Diabetes and Its Complications and The Review of Diabetic Studies, and he acts as an ad hoc reviewer for many other journals.

Dr. Pratley graduated from Wayne State University School of Medicine in Detroit, Michigan, and trained in internal medicine at the University of Michigan in Ann Arbor. He completed Fellowship training in geriatrics and gerontology at the University of Michigan, Johns Hopkins University in Baltimore, and the NIH National Institute on Aging in Baltimore, Maryland. His current research interests include the prevention of diabetes, improving the care for older persons with diabetes, developing new drugs to treat and prevent diabetes and its complications, and understanding the role of the fat cell in increasing the risk of diabetes and heart disease.

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FACULTY

Richard E. Pratley, MD

Stephen D. Wiviott, MD, FACC FACULTY

Executive Director, Clinical Trials Office, Partners HealthCare Senior Investigator Thrombolysis in Myocardial Infarction (TIMI) Study Group Cardiovascular Division, Brigham and Women’s Hospital Associate Professor of Medicine, Harvard Medical School Boston, Massachusetts

Dr. Stephen D. Wiviott graduated from the University of Pennsylvania and Harvard Medical School (HMS, Honors). He served as a Medicine Resident and Chief Medical Resident at Brigham and Women’s Hospital (BWH). Following his medical residency training, he served as a Cardiology fellow at Johns Hopkins Hospital. He is Associate Professor of Medicine at HMS, and a Senior Investigator with the TIMI study group. He attends in the Lown Cardiovascular Intensive Care Unit and general Cardiology service at BWH. As an investigator, Dr. Wiviott has played important roles in the planning, implementation, leadership, and interpretation of multicenter, national, and international clinical trials in acute coronary syndromes including the TRITON-TIMI 38 trial, PRINCIPLE-TIMI 44, and TIMI 38 Coronary Stent Registry. He has also led trials of secondary prevention of cardiovascular disease as global Principal Investigator of DECLARE – TIMI 58 and CAMELLIA – TIMI 61 assessing cardiovascular safety and efficacy of metabolic therapies. Chairman of the TIMI Clinical Events Committee, he is recognized as an expert in event definitions and adjudications. Dr. Wiviott has authored nearly 200 peer-reviewed publications in major medical and cardiovascular journals. He was named in 2014 and 2017 by Thomson Reuters and Clarvate Analytics as one of “The World’s Most Influential Scientific Minds” and in 2016 as a “Highly Cited Researcher,” recognitions inclusive of the top 1% of researchers in Clinical Medicine by citation.

Building on his trials experience, Dr. Wiviott was appointed Executive Director of the Clinical Trials Office (CTO) for Partners HealthCare. The CTO provides contracting, budgeting, and clinical trial management services for Partners hospital investigators and industry sponsors and is tasked with supporting and growing clinical trials research at Partners.

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TARGET AUDIENCE The educational design of this activity addresses the needs of cardiology, endocrinology, and diabetology clinicians involved in the treatment of patients with type 2 diabetes (T2DM).

EDUCATIONAL OBJECTIVES After completing this activity, the participant should be better able to:

PREAMBLE

• Describe the reciprocal pathophysiologic relationships between T2DM and cardiovascular disease (CVD), heart failure (HF), and chronic kidney disease (CKD), including treatment implications • Compare the designs and results of large-scale cardiovascular outcomes trials with sodium-glucose cotransporter-2 (SGLT2) inhibitors for T2DM • Discuss the mechanistic profiles, evidence for clinical benefits, and safety concerns associated with SGLT2 inhibitors as treatment options for patients with T2DM • Intensify treatment regimens for patients with T2DM based on glycemic targets, cardiovascular and renal risks, recent guideline recommendations, and other clinical parameters

STATEMENT OF NEED/PROGRAM OVERVIEW Diabetes disorders afflict more than 30 million Americans, while another 84 million adult Americans have prediabetes.1 Multisystem consequences of T2DM include CVD, HF, and CKD. The pathophysiologic mechanisms underlying T2DM, CVD, HF, and CKD share common characteristics: metabolic changes, a proinflammatory state, and oxidative stress.2 It is critical for providers to be aware of the heightened risk for poor outcomes in their patients with T2DM. Following several cardiovascular outcomes clinical trials with SGLT2 inhibitors, the American Diabetes Association recommends incorporating these agents (and other antihyperglycemic classes, such as glucagon-like peptide-1 receptor agonists), into treatment regimens for T2DM, particularly when CVD risks are elevated.3 The effects of SGLT2 inhibitors on renal glucose reabsorption, along with their ability to lower body weight, cardiac afterload, and blood pressure, translate to a reduction in renal and cardiac adverse events frequently associated with T2DM.4 The established relationships among T2DM, CVD, HF, and CKD necessitate individualized treatment to avoid or mitigate hyperglycemia and these common comorbidities. This live Clinical Issues™ program will address these topics to ensure attendees understand normal glucose homeostasis, the role of maladaptive reabsorption in T2DM, and the benefits SGLT2 inhibitors may have on common comorbidities associated with T2DM as well as their application in clinical practice.

REFERENCES

1. Centers for Disease Control and Prevention. National diabetes statistics report. 2017. https://www.cdc.gov/diabetes/data/statistics/ statistics-report.html. Accessed May 31, 2019.

2. Kovacic JC, Castellano JM, Farkouh ME, Fuster V. The relationships between cardiovascular disease and diabetes: focus on pathogenesis. Endocrinol Metab Clin North Am. 2014;43(1):41-57.

3. Davies MJ, D’Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018;41(12):2669-2701.

4. Toth-Manikowski S, Atta MG. Diabetic kidney disease: pathophysiology and therapeutic targets. J Diabetes Res. 2015;2015:697010.

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PROGRAM AGENDA 6:45 pm-6:55 pm

Preactivity Questionnaire and Faculty Introductions

6:55 pm-7:20 pm

Mechanistic Insights Into T2DM and Common Comorbidities

7:20 pm-7:45 pm

Large-Scale Cardiovascular Outcomes Trials With SGLT2 Inhibitors

7:45 pm-8:15 pm

Updates on Intensifying Therapy in T2DM

8:15 pm-8:30 pm

Audience-Selected Case Studies

8:30 pm-8:45 pm

Postactivity Questionnaire and Q&A Session

PREAMBLE

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 Communications. Global is accredited by the ACCME to provide continuing medical education for physicians.

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 cme@globaleducationgroup.com.

INSTRUCTIONS TO RECEIVE CREDIT In order to receive credit for this activity, the participant must submit a completed evaluation form at the conclusion of the program. You will be emailed a certificate within 4 weeks. If you do not receive your credit at that time, please contact cme@globaleduationgroup.com.

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

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.

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Lawrence Blonde, MD, FACP, MACE

Consultant/Independent Contractor: AstraZeneca, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, sanofi-aventis U.S. LLC; Grant/Research Support: Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, sanofi-aventis U.S. LLC; Speakers Bureau: Janssen Pharmaceuticals, Inc., Novo Nordisk A/S, sanofi-aventis U.S. LLC

Serge A. Jabbour, MD, FACP, FACE

Consultant/Independent Contractor: AstraZeneca; Speakers Bureau: Janssen Pharmaceuticals, Inc.

Richard E. Pratley, MD Consultant/Independent Contractor: AstraZeneca, GlaxoSmithKline, Glytec, LLC, Janssen Pharmaceuticals, Inc., Ligand Pharmaceuticals Incorporated, Eli Lilly and Company, Merck & Co., Inc., Mundipharma International, Novo Nordisk A/S, sanofi-aventis U.S. LLC; Grant/ Research Support: Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals Incorporated, Eli Lilly and Company, Merck & Co., Inc., Mundipharma International, Novo Nordisk A/S, sanofi-aventis U.S. LLC; Speakers Bureau: AstraZeneca, Novo Nordisk A/S Stephen D. Wiviott, MD, FACC

Consultant/Independent Contractor: Arena Pharmaceuticals, Inc., AstraZeneca, Aegerion Pharmaceuticals, Inc., Allergan, Inc., Angel Medical Systems, Inc., Boehringer Ingelheim, Boston Clinical Research Institute, Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Eisai Inc., Eli Lilly and Company, ICON plc, Janssen Therapeutics, Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Servier Pharmaceuticals LLC, St. Jude Medical, Inc., Xoma Biotechnology; Grant/Research Support: Amgen, Arena Pharmaceuticals, Inc., AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo Company, Limited, Eisai Inc., Eli Lilly and Company, Janssen Therapeutics, Merck & Co., Inc., sanofi-aventis U.S. LLC; Other: Spouse is an employee of Merck & Co., Inc.

The planners and managers 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: Lindsay Borvansky

Nothing to disclose

Andrea Funk

Nothing to disclose

Liddy Knight

Nothing to disclose

Ashley Cann

Nothing to disclose

Gena Dolson, MS

Nothing to disclose

Celeste Collazo, MD

Nothing to disclose

Jim Kappler, PhD

Nothing to disclose

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PREAMBLE

The faculty 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 US Food and Drug Administration. Global Education Group (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.

PREAMBLE

DISCLAIMER Participants have an implied responsibility to use the 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 and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

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CLINICAL PRACTICE GUIDELINES

»» Standards of medical care in diabetes—2019.

American Diabetes Association. Diabetes Care. 2019;42(suppl 1):S1-S193. http://care.diabetesjournals.org/content/42/Supplement_1

»» Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm – 2019 executive summary.

Garber AJ, Abrahamson MJ, Barzilay JI, et al. Endocr Pract. 2019;25(1):69-100. https://www.aace.com/publications/algorithm

PATIENT AND CAREGIVER RESOURCES »» American Association of Diabetes Educators https://www.diabeteseducator.org/living-with-diabetes

»» American Diabetes Association

http://www.diabetes.org/research-and-practice/we-support-your-doctor/patient-education-materials.html

»» Centers for Disease Control and Prevention: Diabetes Education Materials https://www.cdc.gov/diabetes/library/educationmaterials.html

»» National Diabetes Education Program

http://ndep.nih.gov/resources/diabetes-healthsense/

SUGGESTED READINGS

»» Renal, metabolic and cardiovascular considerations of SGLT2 inhibition.

DeFronzo RA, Norton L, Abdul-Ghani M. Nat Rev Nephrol. 2017;13(1):11-26. https://www.nature.com/articles/nrneph.2016.170

»» Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention.

Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, et al. Lancet. 2013;382(9889):339-352. https://www.sciencedirect.com/science/article/pii/S0140673613605954

RESOURCE CENTER

»» SGLT-2 inhibitors and cardiovascular risk: proposed pathways and review of ongoing outcome trials.

Inzucchi SE, Zinman B, Wanner C, et al. Diab Vasc Dis Res. 2015;12(2):90-100. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361459/

»» Diabetes and cardiovascular disease: pathophysiology of a life-threatening epidemic.

King RJ, Grant PJ. Herz. 2016;41(3):184-192. https://link.springer.com/article/10.1007%2Fs00059-016-4414-8

»» Diabetes mellitus and heart failure.

Lehrke M, Marx N. Am J Cardiol. 2017; 120(suppl 1):S37-S47. https://www.ajconline.org/article/S0002-9149(17)30804-4/fulltext

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»» Canagliflozin and cardiovascular and renal events in type 2 diabetes.

Neal B, Perkovic V, Mahaffey KW, et al. N Engl J Med. 2017;377(7):644-657. https://www.nejm.org/doi/full/10.1056/NEJMoa1611925

»» Canagliflozin and renal outcomes in type 2 diabetes and nephropathy.

Perkovic V, Jardine M, Neal B, et al. N Engl J Med. 2019. [Epub ahead of print]. https://www.nejm.org/doi/full/10.1056/NEJMoa1811744

»» Diabetic kidney disease.

Thomas MC, Brownlee M, Susztak K, et al. Nat Rev Dis Primers. 2015;1:15018. https://www.nature.com/articles/nrdp201518

»» Diabetic kidney disease: pathophysiology and therapeutic targets.

Toth-Manikowski S, Atta MG. J Diabetes Res. 2015;2015:697010. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430644/

»» SGLT2 inhibition in the diabetic kidney—from mechanisms to clinical outcome. van Bommel EJ, Muskiet MH, Tonneijck L, et al. Clin J Am Soc Nephrol. 2017;12(4):700-710. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383382/

»» Empagliflozin and progression of kidney disease in type 2 diabetes.

Wanner C, Inzucchi SE, Lachin JM, et al. N Engl J Med. 2016;375(4):323-334. https://www.nejm.org/doi/full/10.1056/NEJMoa1515920

»» Dapagliflozin and cardiovascular outcomes in type 2 diabetes.

Wiviott SD, Raz I, Bonaca MP, et al. N Engl J Med. 2019;380(4):347-357. https://www.nejm.org/doi/full/10.1056/NEJMoa1812389

»» SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials.

Zelniker TA, Wiviott SD, Raz I, et al. Lancet. 2019;393(10166):31-39. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32590-X/fulltext

»» 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. https://www.nejm.org/doi/full/10.1056/NEJMoa1504720

»» Design and baseline characteristics of the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes trial (VERTIS-CV).

Cannon CP, McGuire DK, Pratley R, et al. Am Heart J. 2018;206:11-23. https://www.sciencedirect.com/science/article/pii/S0002870318302680

»» Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy.

Perkovic V, et al. New Engl J Med. 2019. [Epub ahead of print]. https://www.nejm.org/doi/full/10.1056/NEJMoa1811744

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RESOURCE CENTER

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Please visit the CLINICAL RESOURCE CENTER for additional information and resources

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