Long-Acting GLP-1 Receptor Agonist Therapy in tpe2 Diabetes Mellitus

Ralph A. DeFronzo, MD,
Chair; John B. Buse, MD, PhD; David D'Alessio, MD


CME Released:
12/14/2012; Valid for credit through 12/14/2013


This activity was developed for
practicing endocrinologists and other healthcare providers involved with
diabetes care who wish to expand their knowledge and experience in diabetes
management.


Given its progressive nature, T2DM
management typically requires increased medication dosages and the stepwise
addition of new therapies over time to sustain glycemic control. To make
appropriate drug selections, particularly to adequately match drug and patient
characteristics, physicians need to understand the mechanisms of all available
drugs; current guidelines do not provide this kind of detailed guidance. Many
current oral therapies have significant limitations, including weight gain,
increased cardiovascular risk, reduction of bone density, gastrointestinal
effects, and hypoglycemia risk, while insulin can result in weight gain and
hypoglycemia. When prescribing for and managing treatment regimens that
typically consist of more than 1 medication, physicians need to be aware of
both the benefits and drawbacks of their choices.


Thus, it is imperative that
physicians and other healthcare providers who treat patients with diabetes stay
up to date on the multiple current and emerging drug classes and formulations,
some of which do not carry the risk of weight gain and its associated
cardiometabolic risk.


One such class are incretin
therapies, including the once- and twice-daily injectable, secretagogue GLP-1
agonists. These compounds bind to GLP-1 receptor cells in the gut, stimulating
glucose-dependent insulin release and inhibiting glucagon release.They have
been used in the US since 2005, when the US Food and Drug Administration (FDA)
approved the first GLP-1 agonist, exenatide. Since then, another drug in this
class, liraglutide, has also been approved. Both are associated with
substantially reduced blood glucose levels, weight loss, lower blood pressure,
improved cholesterol levels, and improved beta-cell function in studies
exceeding 2 years' duration. Earlier this year, exenatide extended release, the
first extended-release GLP-1 agonist, was approved for once-weekly injections.
There are several other extended-release GLP-1 agonists in development; these
drugs will require biweekly, once-weekly, or perhaps even less-frequent
injections.


Upon completion of this activity,
participants should be able to:

1. Review current knowledge on the
   multiple hormonal systems underlying regulation of body fat, body weight,
   pancreatic islet cell function, and overall cardiometabolic health
   
2. Discuss the mechanism of action
   of GLP-1 receptor agonists and how they address the fundamental underlying
   defects of diminished incretin effect, impaired insulin secretion
   (beta-cell failure), and insulin resistance in T2DM
   
3. List the glycemic and nonglycemic
   benefits of GLP-1 receptor agonists in T2DM, as well as the actual risk of
   adverse events and potential safety issues associated with these compounds
   
4. Define patient barriers to
   compliance with injectable drugs and clinical evidence regarding compliance
   with long-acting GLP-1 receptor agonists
   
5. Identify opportunities within
   their own practices to improve patient compliance with injectable
   therapies, including the use of T2DM therapies requiring less-frequent
   injections
   
6. Describe current research findings
   on extended-release GLP-1 receptor agonists, both as monotherapy and in
   combination with other drugs, as well as compared to their once- or
   twice-daily administered counterparts
   

Off-label Use
The faculty does not intend to discuss any off-label or investigational drugs
or devices during the presentations.

Professor of Medicine; Chief, Diabetes
Division, University of Texas Health Science Center, Audie L. Murphy Memorial
Veterans Hospital; Deputy Director, Texas Diabetes Institute, San Antonio,
Texas


Disclosure: Grant/Research Support:
Amylin, Takeda; Board Member/Advisory Panel: Amylin, Boehinger-Ingelheim,
Bristol-Myers Squibb, Novo Nordisk, Takeda; Speakers Bureau: Novo Nordisk

Professor of Medicine; Director, Diabetes
Care Center; Chief, Division of Endocrinology, Department of Medicine,
University of North Carolina School of Medicine, Chapel Hill, North Carolina


Disclosure: Grant/Research
Support/Consultant/Speakers' Bureau*: Amylin, Bayhill Therapeutics, BD
Research, Bristol-Myers Squibb, Dexcom, Eli Lilly, GlaxoSmithKline,
Hoffmann-LaRoche, Intekrin, Intuity Medical, Johnson & Johnson, MannKind,
Merck, Microlslet, Novartis, Novo Nordisk, Osiris, Pfizer, sanofi-aventis,
Transition Therapeutics, Wyeth; Stockholder: Insulet

*These relationships are all under contract between the companies and the
University of North Carolina, and provide no direct financial benefit to Dr
Buse.

Director, Division of Endocrinology,
Diabetes and Metabolism; Professor of Medicine, University of Cincinnati;
Chief, Section of Endocrinology, Cincinnati Veteran Affairs Medical Center,
Cincinnati, Ohio


Disclosure: Grant/Research Support:
Ethicon Endosurgery, MannKind; Consultant: Amylin, Eli Lilly, Novo Nordisk,
Takeda, Zealand

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