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Therapy of Type 2 Diabetes Mellitus: UPDATE

Therapy of Type 2 Diabetes Mellitus: UPDATE. Glycemic Goals in the Care of Patients with Type 2 Diabetes- 2013 ADA and AACE Guidelines: Room For Improvement (Be HAPPY/ Avoid Burnout, While Caring for Patients with DM). Stan Schwartz MD, FACP, FACE Affiliate, Main Line Health System

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Therapy of Type 2 Diabetes Mellitus: UPDATE

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  1. Therapy of Type 2 Diabetes Mellitus: UPDATE Glycemic Goals in the Care of Patients with Type 2 Diabetes- 2013 ADA and AACE Guidelines: Room For Improvement (Be HAPPY/ Avoid Burnout, While Caring for Patients with DM) Stan Schwartz MD, FACP, FACE Affiliate, Main Line Health System Clinical Associate Professor of Medicine, Emeritus, U of Pa. Part 5

  2. 8-10x 2-4x

  3. exenatide Effect on hypothalamus, Slower gastric emptying, Not related to nausea • WEEK WEIGHT Dec.- Not correlated to nausea 3

  4. DPP-4 Inhibitors and CV Events:A Meta-analysis 0.001 0.1 1 10 1000 DPP4i better DPP4i worse 52% reduction in risk for CV events compared to other oral agents or placebo. Patil HR, et al. Am J Cardiol. 2012;110(6):826-833.

  5. SavorN Engl J Med. 2013 Oct 3;369(14):1317-1326. Epub 2013 Sep 2.Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus.Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B,Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I; the SAVOR-TIMI 53 Steering Committee and Investigators.

  6. Exenatide and CV outcomes- 430,000 patients-near 40,000 on exenatide Risk of Cardiovascular Disease Events in Patients With Type 2 Diabetes Prescribed the Glucagon-Like Peptide 1 (GLP-1) Receptor Agonist Exenatide Twice Daily orOther Glucose-Lowering Therapies A retrospective analysis of the LifeLink database JENNIE H. BEST, PHD, Diabetes Care 34:90–95, 2011 1

  7. Nausea Story Observations • The most common AEs associated with exenatide (vs placebo) in three 30-week, placebo-controlled clinical trials were nausea (44% vs 18%), vomiting (13% vs 4%), diarrhea (13% vs 6%), • 5 years later, monotherapy study was only 19%; e.g.: learned how to use it- stop eating when full • Both exenatide/liraglutide, nausea decreases over time • Exenatide-QW 1/3 risk of nausea as liraglutide 1.8 mg/d • Etiology- • Oversensitive hypothalamic sensitivity • Slower gastric emptying; patients keep eating after first sense of fullness • High fiber, high fat meals • In Hospital- • TEACH PATIENTS TO STOP EATING AT FIRST SENSE OF FULLNESS!! • Patients eat slowly, decreased speed of eating, decreased quantity of eating, less fatty meals • The ~1 % hypothalamic nausea can be treated with metochlopromide/ ondansetron-Diabet Med. 2010 Oct;27(10):1168-73. doi: 10.1111/j.1464-5491.2010.03085.x.

  8. Pancreatic Cancer- NOT • 15 yr. Age difference, control to incretin • Compared type 1 to type 2 pancreases • Polyclonal nonspecific antibody vs monoclonal antibody (proves no GLP1 receptors on epithelium) • Alpha cell hyperplasia Butler saw is not cell type leading to pancreatic cancer

  9. GLP-1 Receptors on rodent C- cells, but not on Human C-Cells Endo, 2010 ADA, 2013, EASD 2013 Exenatide-QW carries same warning

  10. Patient Types/ Situations 0.Treat Late Post-Prandial Hypoglycemia 1. Prevention / Delay of DM 2. Cardiovascular- as above, likely reduced CV outcomes with weight neutrality, no undue hypoglycemia 3. Guideline based 4. Approach to Weight reduction in Diabetes 5. Type 1/ Type 2 on insulin (on/off label) 6. Discontinue Insulin 7. Hospital/ stress/ steroid dm

  11. Changes in Glycemia and Weight in3 Studies of Exenatide vs Insulin Heine et al1 Nauck et al3 Barnettet al2 Heine et al1 Barnettet al2 Nauck et al3 10 9 Change inA1C, % 8 ADA GOAL 7 -0.9% -1.0% -1.4% -1.1% -1.4% -1.1% 6 Glargine, Once Daily Insulin Aspart, 70/30 Exenatide 4 3 2 1 Change in Weight, kg 0 +2.9 kg +1.8 kg +2.3 kg -1 -2 -2.2 lb -2.3 kg -3 -2.5 kg ie: ALWAYS USE GLP-! BEFORE GO TO INSULIN 1. Heine R, et al. Ann Intern Med. 2005;143:559-569. 2. Barnett AH, et al. Clin Ther. 2007;29:2333-2348. 3. Nauck MA, et al. Diabetologia. 2007;50:259-267.

  12. Weight Loss in Obese Non-Diabetics over 2 years with Lira-glutide

  13. Incretins in Type-2 Patients My Experience: Fewer patients need bolus insulin: DPP-4 inh=~50% GLP-1 RA=~ 20%

  14. GLP-1 RAs in Type 1 Diabetes Liraglutide Exenatide with a meal Data Suggests: less dawn effect, less variability, decrease insulin doses, less hypoglycemia Recent epiphany: I prescribe less pump therapy

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