1. New Insulin Formulations Guillermo Umpierrez, MD, FACP, FACE Professor of Medicine Emory University School of Medicine Part 1

2. BANTING-1891-1941 & BEST-1899-1978 First commercial insulin

3. Milestones in Insulin Development Tattersall RB. In: Pickup JC, Williams G, eds. Textbook of Diabetes. 3rd ed. Blackwell Science: Malden, MA; 2003:1.1-1.22; Drugs@ FDA; http://diabetes.webmd.com/news/20071018/pfizer-quits-inhaled-insulin-exubera. 2013 Degludec (2013) In development: Degludec U-200 Glargine U-300 Pegylated Lispro Biosimilars 2014

4. Currently Available Basal Insulins Lucidi D, et al. Diabetes Care. 2011;34:1312-1314. Niswender K, et al. Clin Diabetes. 2009;27:60-68.

6. Insulin Glargine vs NPH Insulin Added to Oral Therapy: FPG and HbA 1c Riddle M, et al. Diabetes Care 2003;26:3080−6. 04812162024 6 7 8 9 HbA 1c (%) Insulin glargine NPH 756 patients previously treated with 1―2 OHAs and HbA 1c >7.5% Mean daily insulin dose Insulin glargine: 47 units NPH: 42 units Time (weeks) 10 7 5 04812162024 FPG (mmol/l) Time (weeks) 6 8 9

7. Treat to Target Trial: Frequency of Hypoglycemia Riddle MC, et al. Diabetes Care. 2003;26:3080-3086 900 Glargine NPH 24120 800 Time (days) 700 600 500 400 300 200 100 0 0487296144 Cumulative number of events Documented PG< 56 mg/dL (3.1 mmol/L) Glargine NPH 168 41% RRR P <0.003

9. Giugliano et al. Diabetes Research & Clinical Practice 92 (2011) 1–10 29 trials, with 17,588 patients HbA1c < 7% was achieved in 41.4% (95% CI, 35.6–47.4%). First insulin treatment, lower insulin and use of 2 oral drugs were predictors of response. Hypoglycemia ranged from 0 to 4.71 events/patient/30 days Weight gain ~1.75 kg HbA1c < 7% was achieved in 41.4% (95% CI, 35.6–47.4%)

10. ProductOnset, hPeak, h Effective Duration, h Human biphasic insulin 70% NPH/30% regular 0.5-1Dual10-16 Analogue biphasic insulin 75% NPL/25% lispro < 0.25Dual10-16 50% NPL/50% lispro < 0.25Dual10-16 70% aspart protamine/30% aspart < 0.25Dual15-18 American Diabetes Association. Practical Insulin: A Handbook for Prescribing Providers. 3rd ed. 2011:1-68. Available Premixed/Biphasic Insulins NPH, neutral protamine Hagedorn; NPL, neutral protamine lispro suspension.