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New Insulin Formulations

New Insulin Formulations. Guillermo Umpierrez, MD, FACP, FACE Professor of Medicine Emory University School of Medicine Part 2. Insulin Glargine vs 70/30 Premixed Insulin in OHA Failures.

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New Insulin Formulations

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  1. New Insulin Formulations Guillermo Umpierrez, MD, FACP, FACE Professor of Medicine Emory University School of Medicine Part 2

  2. Insulin Glargine vs 70/30 Premixed Insulin in OHA Failures N=371 insulin-naïve patientsInsulin Glargine + OADs vs twice-daily human NPH insulin (70/30)Follow-up: 24 weeks Twice-daily premixed insulin Insulin Glargine + OADs p=0.0003 9 5 5.7 1.3% 1.7% 4 8 p=0.0009 Hypoglycemia* (events/patient year) 3 7.5% HbA1c (%) 7 7.2% 2.6 2 6 1 5 0 *Confirmed symptomatic hypoglycemia (blood glucose <60 mg/dl [<3.3 mmol/l]) Janka H, et al. Diabetes Care 2005;28:254−259.

  3. Stepwise Intensification: 1-2-3 Study Design Group 1:GLAR + OADs + 1GLU N=115 A1C >7.0% (n=343) Poorly controlled on OADs (N=785) Group 2: GLAR + OADs + 2GLU N=113 Switched to GLAR for 14 weeks Group 3: GLAR + OADs + 3GLU N=115 Randomization and 24 week F/U • Insulin glulisine was administered 0-15 minutes before greatest glycemic index meal • Initial glulisine dose was 1/10th of the glargine does at randomization • Weekly titration to target PPG 70-109 mg/dL and HS level 70-129 mg/dL OADs were continued. GLAR = insulin glargine; GLU = insulin glulisine; OADs=oral antidiabetic agents. Davidson MB et al. Endocr Pract. February 16, 2011.

  4. A1C Change From Baseline to Week 24 • Following 14-week run-in with insulin glargine • Mean A1C decreased from >10.0% to ~8.0% • 288 patients achieved A1C 7.0% • Final dose was 0.55 U/kg regardless of reaching target mITT = modified intent to treat. Davidson MB et al. Endocr Pract 2011

  5. Characteristics of Available Basal Insulin Analogs Benefits over NPH • Longer duration of action • Less variability • Less weight gain • Less hypoglycemia Room for Improvement • More consistent 24+ hour coverage • Flat time-action profile • Less day-to-day variability • Less weight gain • Less hypoglycemia • More suppression of hepatic glucose production Simon ACR. Diabetes Technol Ther. 2011;13(suppl 1):S103-108. Grunberger G. Diab Obes Metab. 2013;15(suppl 1):1-5.

  6. *Glargine U-300 *Degludec *Pegylated Lispro New Basal Insulin Formulations * Not FDA Approved

  7. High concentration glargine (U300)* • U300 insulin glargine offers a smaller depot surface area leading to a reduced rate of absorption • Provides a flatter and prolonged pharmacokinetic and pharmacodynamic profiles and more consistency • Half-life is ~23 hours • Steady state in 4 days • Duration of action ≤36 hours *Not FDA approved Garber AJ. Diabetes Obesity Metab; [Epub ahead of print; published online 31 Oct 2013]. Owens DR, et al. Diabetes Metab Res Rev. 2014;30(2):104-19. Steinstraesser A, et al. Diabetes Obes Metab. 2014 Feb 26. [Epub ahead of print]. http://www.australianprescriber.com/magazine/19/3/76/8. Accessed March 11, 2014.

  8. Pharmacokinetics of U-300 Insulin Glarginea in Healthy Volunteers 35 30 U-100 0.4 U/kg (n = 24) 25 U-300 0.4 U/kg (n = 23) 20 Concentration (uIV/mL) 15 10 5 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 Time a U-300 insulin glargine is not FDA approved for clinical use. Becker R, et al. European Patent EP 2 387 989 A2. 2011.

  9. Pharmacodynamics ofU300 Glargine vs U100 Glargine 3.0 U100 0.4 U/kg-1 SC Injection 2.5 U300 0.4 U/kg-1 U300 0.6 U/kg-1 2.0 GIR (mg/kg-1 min-1)* U300 0.9 U/kg-1 1.5 1.0 0.5 0 0 6 12 18 24 30 36 Time (hours) • The U-300 glargine has a flatter more prolonged effect • The time it takes for 50% of the effect of a single injection • U-100 = 12.1 hours • U-300 = 16.7 hours GIR = glucose infusion rate. Tillner J, et al. Poster 920P 73rd ADA Scientific Sessions June 21-25, 2013, Chicago, IL. http://ada.apprisor.org/epsAbstract.cfm?compid=1&id=1. Accessed March 21, 2014.

  10. U300 Glargine vs U100 Glargine in Type 2 Diabetes 8.5 Mean change in A1C for both treatment groups -0.83% No difference inA1C change 8.0 Mean A1C (%) 7.5 U300 7.0 U100 6.5 Baseline Week 12 Month 6 Month 6LOCF Time Riddle MC et al. Presentation 43-LB 73rd ADA Scientific Sessions June 21-25, 2013, Chicago, IL. http://ada.apprisor.org/epsAbstract.cfm?compid=1&id=1. Accessed March 21, 2014.

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