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Kolterman OG et al J Clin Endocrinol Metab 2003

Exenetide and beta cell responses. Kolterman OG et al J Clin Endocrinol Metab 2003. Exenetide reduces A1C. Exenetide reduces A1C. Exenetide and insulin glargine. Exenetide and insulin glargine. Exenetide and insulin glargine. Exenetide and insulin glargine.

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Kolterman OG et al J Clin Endocrinol Metab 2003

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  1. Exenetide and beta cell responses Kolterman OG et al J Clin Endocrinol Metab 2003

  2. Exenetide reduces A1C

  3. Exenetide reduces A1C

  4. Exenetide and insulin glargine

  5. Exenetide and insulin glargine

  6. Exenetide and insulin glargine

  7. Exenetide and insulin glargine Heine et al. Annals Int Med 2005

  8. Algorhythms for diabetes management • All agree: • lifestyle modification (diet, exercise, smoking cessation) • Reduce cardiometabolic risk (lipids, BP, ASA 325 mg) • metformin titrated to max tolerated dose • Intensify Rx if target A1C 6 to 7% • No agreement on next step: • SU e.g. glipizide XR • TZD e.g. pioglitazone, rosiglitazone • incretin mimetics e.g. exenatide (others on the way) • DP4 inhibitors, e.g. sitagliptin (others on the way) • insulin (? Which one)

  9. Most Patients on Diabetes Therapies Not Reaching A1C < 7% 100 27% 32% 80 15% % of Subjects > 9% 19% 60 A1C Value 8%–9% 20% 7%–8% 22% 40 < 7% 38% 20 27% 0 Oral Insulin +/- oral *NHANES III = Third National Health and Nutrition Examination Survey. Harris MI, et al. Diabetes Care. 1999;22:403–408.

  10. Clinical inertia: failure to intensify treatment of a patient who is not at their evidence-based A1C goal

  11. Progressive Decline of β-Cell Function in the UKPDS 100 80 60 -Cell Function (% ) 40 20 0 10 9 8 7 6 5 4 3 2 1 0 1 2 3 4 5 6 Years Adapted from UK Prospective Diabetes Study (UKPDS 16) Group. Diabetes. 1995;44:1249-1258.

  12. 4T (Treating to Target in Type 2 DM) Year 1 Comparison of threesingle insulin regimens, added to OADs* Years 2 and 3 If HbA1c >6.5%, stop sulfonylurea and add a second insulin formulation Add biphasic insulintwice a day Add prandial insulinat midday R 708T2DMon dual OAD Add prandial insulinthree times a day Add basal insulinbefore bed Add basal insulinonce (or twice) daily Add prandial insulin three times a day * Intensify to a combinationisulin regimen in year one if unacceptable hyperglycaemia N Engl J Med 2007; 357: 1716-30

  13. Biphasic * * Prandial * * * * * * * <> Basal * * Injection Self-measured glucose * 4T (Treating to Target in Type 2 DM) N Engl J Med 2007; 357: 1716-30

  14. Dosing example of patient with type 2 diabetes on intensive insulin • A 56-year-old man with long-standing DM2, CAD, s/p MI, and recent CABG • Blood sugars high in hospital, where he was started on analog premix insulin 10 units bid • Insulin dose titrated over phone and during office visits • Office visit 6 months after cardiac surgery

  15. Dosing example (cont’d) • No longer on oral agents • Now taking aspart mix 70/30 18 units with breakfast and 24 units with supper • Blood sugars ranging from 52 mg/dL to 265 mg/dL • A1C was 7.1%

  16. Dosing example (cont’d) • Patient had retired early and used to enjoy playing golf at least twice a week • On golf days, he would develop hypoglycemia around midday • At one golf outing, he held his morning insulin, but his fingerstick went up to over 300 mg/dL

  17. Solution (cont’d) • Daily insulin requirement = 24 + 18 = 42 units • Start basal insulin: about 50% of total insulin requirement = 42 units/d ÷ 2 = 21 units • Use fast-acting analog only with meals when patient is going to eat; vary time of administration on golf days; meet with dietitian CDE; adjust dose according to CHO to be consumed CDE = certified diabetes educator; CHO = carbohydrates.

  18. Solution (cont’d) • Typical insulin-to-carb ratios 1:3 to 1:20 • This patient 1:5 • 31 g cereal + 15 g apple • 46 g carbs / 5 = 9 units aspart • 4 months later, A1C 6.4%; enjoying golf; lost 3 pounds; no hypoglycemia

  19. Amylin • Reported in 1987 • 37-amino acid peptide Amylin Insulin Unger RH, Foster DW. Williams Textbook of Endocrinology (8th edition) 1992; 1273-1275 Photographs reprinted with permission of Elsevier

  20. Amylin Activates Specific Areas of the rat brain amylin 10-8 M amylin 10-8 M amylin 10-8 M AC187 10-6 M 16 12 Spikes/s 8 4 0 0 30 60 90 120 150 180 Time (min) Rowland, et al. Regul Pept 1997; 71:171-174 Photographs from Riediger T, et al. Am J Physiol Regul Integr Comp Physiol 2001; 281:R1833-R1843

  21. * * * * * * * pramlintide and glucose fluctuations Baseline (Insulin Only) 6 Months (Insulin + 120 mcg SYMLIN) 220 200 180 Glucose (mg/dL) 160 140 120 bedtime pre-lunch pre-dinner post-lunch pre-breakfast post-breakfast post-dinner n = 166 at baseline; observed cases; Mean (SE); *P-values for all data points <0.05 Data on file, Amylin Pharmaceuticals, Inc. See safety information with Boxed Warning in this presentation and the accompanying Prescribing Information

  22. New technology

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