Multidimensional Outcomes 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.

There is no registration fee for attending this program; however, seating is limited. Preregistration does not guarantee seating. We recommend arriving at the symposium location early.

This event is not part of the official Scientific Sessions 2019 as planned by the AHA Committee on Scientific Sessions Program.

MEDICAL COMMUNICATIONS INQUIRIES info@integritasgrp.com integritasgrp.com

FACULTY FACULTY

Christopher P. Cannon, MD Education Director, Cardiovascular Innovation Preventive Cardiology Section Brigham and Women’s Hospital Professor of Medicine, Harvard Medical School Boston, Massachusetts

Dr. Christopher Cannon is a Professor of Medicine at Harvard Medical School, and senior physician in the Cardiovascular Division at Brigham and Women’s Hospital. Education Director in the Cardiovascular Innovation group, he has worked for 25 years as an investigator in the TIMI Study Group and for 5 years with the Harvard Clinical Research Institute (now Baim Institute).

He earned his medical degree from Columbia University College of Physicians and Surgeons in New York and did internal medicine residency at Columbia Presbyterian Medical Center and cardiovascular fellowship at Brigham and Women’s Hospital.

Dr. Cannon has published over 1000 original articles, reviews, or book chapters on acute coronary syndromes and their prevention and has authored or edited 18 books. He has received numerous awards, including leadership awards from the American College of Cardiology, American Heart Association, and National Lipid Association.

He has been principal investigator of more than 20 multicenter clinical trials, including TACTICS-TIMI 18, PROVE IT, IMPROVE IT, and RE-DUAL PCI trials. He is currently working on clinical trials, registries, and quality improvement projects in the fields of acute coronary syndromes, atrial fibrillation, diabetes, lipids, and prevention. In his new role at Brigham Cardiovascular Medicine Innovation, he aims to help develop and implement quality improvement programs, including pragmatic clinical trials, into new care delivery systems.

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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 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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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 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 Clarivate 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 This activity is intended for cardiologists, internists, and other clinicians who treat patients with type 2 diabetes mellitus (T2DM).

EDUCATIONAL OBJECTIVES

PREAMBLE

After completing this activity, the participant should be better able to: • Describe the pathophysiologic relationships between T2DM and cardiovascular disease (CVD), heart failure (HF), and chronic kidney disease (CKD), including implications for antihyperglycemic treatment • 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 • Collaborate with other clinicians to treat patients with T2DM based on cardiovascular and renal risks, recent guideline recommendations, and other clinical parameters

PROGRAM DESCRIPTION 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 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 established relationships among T2DM, CVD, HF, and CKD necessitate individualized treatment to avoid or mitigate hyperglycemia and these common comorbidities. Cardiologists, in particular, must be knowledgeable about how updates to guidelines outside of the cardiology space have evolved, allowing them to contribute to multidisciplinary best-practices for the treatment of patients with T2DM and common comorbidities. This live Interactive Exchange™ program will address these topics to ensure attendees understand the role of maladaptive glucose reabsorption in T2DM, the benefits SGLT2 inhibitors may have on common comorbidities associated with T2DM, and the role the cardiologist plays in diabetes management.

REFERENCES

1. Centers for Disease Control and Prevention. National diabetes statistics report. 2017; https://www.cdc.gov/diabetes/data/statistics/ statistics-report.html. Accessed November 5, 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. American Diabetes Association. Standard of Medical Care in Diabetes – 2019. Diabetes Care. 2019;42(suppl 1):S1-S193.

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PROGRAM AGENDA 7:00 pm

Preactivity Questionnaire and Faculty Introductions

7:05 pm

Mechanistic Insights Into T2DM and Common Comorbidities

7:20 pm

Large-Scale Cardiovascular Outcomes Trials With SGLT2 Inhibitors

7:40 pm

Tailoring Therapy for Patients With T2DM: How Can the Cardiologist Contribute?

8:00 pm

Audience-Selected Case Studies

8:15 pm

Postactivity Questionnaire and Q&A Session

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.

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 designates this live activity for a maximum of 1.5 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 e-mailed 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.

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PREAMBLE

PHYSICIAN ACCREDITATION STATEMENT

DISCLOSURE OF CONFLICT OF INTEREST 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.

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: Christopher P. Cannon, MD Consultant/Independent Contractor: Aegerion Pharmaceuticals, Inc., Alnylam Pharmaceuticals Inc., Amarin Corporation, Amgen Inc., Applied Therapeutics, Inc., Asendia USA, Boehringer-Ingelheim, Bristol-Myers Squibb, Corvidia Therapeutics Inc., HLS Therapeutics Inc., Innovent Biologics, Inc., Janssen Pharmaceuticals, Inc., Kowa Pharmaceuticals America, Inc., Merck & Co., Inc., Pfizer Inc., sanofi-aventis U.S. LLC; Grant/ Research Support: Amgen Inc., Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo Company, Limited, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc. Serge A. Jabbour, MD, FACP, FACE Consultant/Independent Contractor: AstraZeneca; Speakers Bureau: Janssen Pharmaceuticals, Inc. 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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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 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.

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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PREAMBLE

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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

» 2018 ACC expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes and atherosclerotic cardiovascular disease: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways.

Das SR, Everett BM, Birtcher KK, et al. J Am Coll Cardiol. 2018;72(24):3200-3223. https://www.sciencedirect.com/science/article/pii/S0735109718384985?via%3Dihub

» 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://journals.aace.com/doi/full/10.4158/CS-2018-0535?=

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

» American Diabetes Association https://www.diabetes.org/resources

» Centers for Disease Control and Prevention: Diabetes Education and Support https://www.cdc.gov/diabetes/managing/education.html

» National Diabetes Education Program

https://www.niddk.nih.gov/health-information/communication-programs/ndep

SUGGESTED READINGS

RESOURCE CENTER

» 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

» 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

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» 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

» Canagliflozin and cardiovascular and renal outcomes in type 2 diabetes mellitus and chronic kidney disease in primary and secondary cardiovascular prevention groups.

Mahaffey KW, Jardine MJ, Bompoint S, et al. Circulation. 2019;140(9):739-750. https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.119.042007?url_ver=Z39.88-2003&rfr_ id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed

» Dapagliflozin in patients with heart failure and reduced ejection fraction.

McMurray JJV, Solomon SD, Inzucchi SE, et al. N Engl J Med. 2019. [Epub ahead of print] https://www.nejm.org/doi/full/10.1056/NEJMoa1911303?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_ dat=cr_pub%3dpubmed

» Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE-TIMI 58 randomised trial.

Mosenzon O, Wiviott SD, Cahn A, et al. Lancet Diabetes Endocrinol. 2019;7(8):606-617. https://www.thelancet.com/journals/landia/article/PIIS2213-8587(19)30180-9/fulltext

» 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 MJ, Neal B, et al. N Engl J Med. 2019;380(24):2295-2306. https://www.nejm.org/doi/full/10.1056/NEJMoa1811744

RESOURCE CENTER

» 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/

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» 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.

RESOURCE CENTER

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

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NOTES

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Please visit the CLINICAL RESOURCE CENTER for additional information and resources

ExchangeCME.com/T2DMResources19

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