1. MARGARITA SIANOSYAN, DOCTOR OF PHARMACY CANDIDATE, LECOM COLLEGE OF PHARMACY GLP-1 Analogs and Lifestyle Modifications

2. Overview  GLP-1 analog’s role in the body  Available GLP-1 analogs on the market  Advantages over other anti-diabetic agents  Benefits when combined with lifestyle modifications  Importance of healthy diet, physical activity, and sleep with GLP-1 analogs  Nutrition and physical activity recommendations

3. GLP-1 in Type 2 Diabetes Ganda, Om. Diabetes and the GI Tract: Important Interrelationship. Medscape reference. WebMD 2011.

4. GLP-1 Analogs  Synthetic and structurally-altered version of naturally produced hormone  Mimic physiological actions of GLP-1  Naturally produced GLP-1 are rapidly inactivated by (dipeptidyl-peptidase 4) DPP-4 enzyme  Half life is 1-2 minutes  GLP-1 analogs are resistant to inactivation by DPP-4 enzyme and stay longer in the body  Work only in presence of glucose Dungan K. Glucagon-like peptide-1-based therapies for the treatment of type 2 diabetes mellitus. In: UpToDate, Nathan, DM (Ed), UpToDate, Waltham, MA 2012.

5. Mechanisms of Action  Glucose-dependent insulin production  Stimulates beta-cells and causes insulin secretion  Inhibits glucagon secretion  Delays gastric emptying  Induces satiety and decreases food intake  Improves beta-cell function and proliferation (animal studies) Conetta C, Patel, M. (2012, February 22). GLP-1 Analogs and DeFronzo's Octet. Diabetes in Control. Retrieved September 5, 2012, from http://www.diabetesincontrol.com/articles/features/12372 http://www.soc- bdr.org/e4/e887/volRdsVolumes5237/issRdsIssues5874/chpRdsChapters5886/strRdsArticles5887/ index_en.html?preview=preview&showfulltext=1

6. Satiety and Food Intake  Long term weight loss  Exact mechanism is unclear  Acts on hypothalamic feeding centers Conetta C, Patel, M. (2012, February 22). GLP-1 Analogs and DeFronzo's Octet. Diabetes in Control. Retrieved September 5, 2012, from http://www.diabetesincontrol.com/articles/features/12372 http://www.funderstanding.com/educators/brain-anatomy/

7. GLP-1 Analogs on the Market  Used as an adjunct to diet and exercise to improve glycemic control  Administered by subcutaneous injection  Byetta (Exenatide) – twice daily SQ injection  Victoza (Liraglutide) – once daily SQ injection  Bydureon (extended-release Exenatide) – once weekly SQ injection Dungan K. Glucagon-like peptide-1-based therapies for the treatment of type 2 diabetes mellitus. In: UpToDate, Nathan, DM (Ed), UpToDate, Waltham, MA 2012.

8. Safety Profile  Mild or moderate nausea  Titrating dose may limit nausea  Diarrhea  Headaches  Dizziness  Hypoglycemia when taken with sulfonylureas  Rare cases of acute pancreatitis and renal dysfunction  Exenatide should not be used in patients with creatinine clearance <30 mL/min McCulloch DK, Munshi M. Treatment of type 2 diabetes mellitus in the elderly patient. In UptoDate, Nathan DM, Schmader KE (Ed), UpToDate, Waltha, MA.2012. http://www.uptodate.com/contents/treatment-of-type-2-diabetes-mellitus-in-the-elderly-patient

9. GLP-1 with other Anti-diabetics  Can be used alone or in combination with other anti-diabetic agents  Combination with dipeptidyl-peptidase-4 (DPP-4) inhibitors is not recommended and is not FDA approved Hester, SA. Pharmacist’s Letter. Combining a GLP-1 Agonist and a DPP-4 Inhibitor for Type 2 Diabetes. Stockton, CA: Therapeutic Research Faculty; [online] http://www.pharmacistsletter.com. September 5, 2012. http://www.ehow.com/how_7433049_use-byetta-pen.html

10. In Comparison to Other Anti-diabetics  Less incidence of hypoglycemia  Greater reduction in A1C levels  Weight reduction  Undesirable effects of other anti-diabetic agents can lead to non-adherence to medications Diabetes Obes Metab. (2012, April 9). GLP-1 a Good Choice for Glycemic Control?. Diabetes in Control. Retrieved September 5, 2012, from http://www.diabetesincontrol.com/articles/53-diabetes- news/12658-glp-1-a-good-choice-for-glycemic-control http://www.freediabetestestsupplies.com/cinnamon-diabetes-natural- cure/

11. Cardiovascular Health  Primary cause of death in Type 2 Diabetes patients is cardiovascular disease (CVD)  GLP-1 agonists lower blood pressure and cholesterol  Increased cardiac contractility and protection against ischemia Spellman CW. (2010). Pharmacology of GLP-1 Agonists: Describing the Therapeutic Potential to Patients. The Journal of the American Osteopathic Association, 11(2), eS10-eS14. Retrieved September 5, 2012 from http://www.jaoa.org/content/111/2_suppl_1/eS10.full http://www.virtua.org/health/cardiovascular-health.aspx

12. Adjunct to Diet and Weight Control  Works best when combined with healthy diet and physical activity  Diet and weight control  Slows progression to Type 2 diabetes  Prevents complications Conetta C, Patel, M. (2012, February 22). GLP-1 Analogs and DeFronzo's Octet. Diabetes in Control. Retrieved September 5, 2012, from http://www.diabetesincontrol.com/articles/features/12372 http://www.northcentraliaredcross.org/wp-content/uploads/2012/03/Healthy-Foods_C.gif

13. Medical Nutrition Therapy (MNT)  “Nutritional diagnostic, therapy, and counseling services for the purpose of disease management, which are furnished by a registered dietitian or nutrition professional.”  Key component in preventing diabetes, managing diabetes, and preventing associated complications  Covered by Medicare and many other private and state insurance plans American Diabetes Association. Medical Nutrition Therapy: A Key to Diabetes Management and Prevention-2010. Clinical Diabetes. 2010;28:12-18

14. Medical Nutrition Therapy (MNT)  Current literature supports MNT as an effective method for treating diabetes  18 studies reviewed by ADA  8 were randomized controlled trials  Intervention groups had greater improvements in A1C levels and fasting plasma glucose  Lifestyle modifications play an important role in managing diabetes American Diabetes Association. Medical Nutrition Therapy: A Key to Diabetes Management and Prevention-2010. Clinical Diabetes. 2010;28:12-18 http://www.cvmc.org/hospital/departments-services/patient-support- services/nutrition-diabetes-counseling

15. Diet  Important to reinforce healthy diet  Types of foods  Limiting foods high in sugar, salt, and fat  Frequency  Eating smaller portions throughout the day  Portion control  Keeping track of carbohydrate intake American Diabetes Association. Medical Nutrition Therapy: A Key to Diabetes Management and Prevention-2010. Clinical Diabetes. 2010;28:12-18 http://www.saintshealthymarriages.com/healthy-diet-plans/

16. Nutrition  Complex carbohydrates (55%), protein (20%), healthy fats (25%)  High fiber carbohydrate foods  Saturated fat intake of <7% of total calories  Minimal trans fat intake American Diabetes Association. Medical Nutrition Therapy: A Key to Diabetes Management and Prevention-2010. Clinical Diabetes. 2010;28:12-18 http://concordweightloss.com/2011/05/03/downsize-portions-for-better-weight-control/

17. Physical Activity  At least 150 minutes per week of moderate-intensity aerobic physical activity  50-70% of maximum heart rate  Resistance training three times a week American Diabetes Association. Medical Nutrition Therapy: A Key to Diabetes Management and Prevention-2010. Clinical Diabetes. 2010;28:12-18 http://extrachapter.com/exercise-and-diabetes/

18. Weight Control  Even small amounts of weight loss can improve glycemic control  Changes in BMI can reduce A1C and blood pressure  Improve lipid levels  Reduce cardiovascular risk factors American Diabetes Association. Weight Loss, Glycemic Control, and Changes in Cardiovascular Biomarkers in Patients With Type 2 Diabetes Receiving Incretin Therapies or Insulin in a Large Cohort Database-2010. Diabetes Care. 2010; 33:1759-1765. http://www.askcms.com/weight-loss/natural-weight-loss-supplements/

19. Sleep  In addition to healthy diet and exercise, sleep also has an important role in weight control  Study found that middle- aged, overweight men who slept 8.5 hours burned more fat than patients that slept 5.5 hours  Elevated levels of ghrelin in the blood Ann Intern Med. 2010;153:435-441, 475-476 www.adultspancounseling.com/wp-content/uploads/2008/04/ManSleeping.jpg

20. Conclusion  GLP-1 analogs have several mechanisms of action in the body.  GLP-1 analogs’ advantages over other anti-diabetic agents include less hypoglycemia, better A1C control, no weight gain, and cardioprotection.  GLP-1 analog therapy is used as an adjunct to healthy diet and exercise.  Healthy lifestyle modifications are necessary for successful treatment.