1. Insulins and Insulin Delivery Rob Dyer 6 February 2009

3. Miss RL – HbA1c Normal range Target Age 10 Age 17

4. Glycaemic excursion and Premixed insulin

5. DCCT Effect of intensive therapy on complications and hypoglycaemia

7. Food Comparisons How much carbohydrate?

9. SALAD MEAL 15g Lettuce minimal Cucumber " Tomatoes " Radish " Red Pepper " Cold chicken " Mayonnaise " Crisps 15g

10. Italian Meal Garlic Bread Whole Pizza Ice Cream ???g

11. Italian Meal Garlic Bread 70g Whole Pizza 100g Ice Cream 30g 200g

16. 1530 Levemir® vs. NPH in treat-to-target trial: Hypoglycaemia Hypoglycaemia Hermansen K, et al., Diabetologia 2004;47(Supplement 1):A273

18. Within-patient variability with NPH insulin Selected clamp profiles on 4 identical study days for 8 out of 17 subjects on NPH who completed the study The CV for all 17 patients on NPH who completed the study was 68% Heise, T. et al., Diabetes, 2004; Vol. 53: 1614-1620 Data on file: InsDet 09 2004

19. Within-patient variability with Levemir ® Selected clamp profiles on 4 identical study days for 8 out of 18 subjects on Levemir ® who completed the study The CV for all 18 patients on Levemir ® who completed the study was 27% Heise, T. et al., Diabetes, 2004; Vol. 53: 1614-1620 Data on file: InsDet 09 2004

20. HbA1c (%) Post- Baseline Post-CSII Post-TIFA Changes in HbA1c during transfer to Pump therapy (CSII) Individual patients

21. Torbay CSII First 11 patients

25. Randomisation N Engl J Med 2007; 357: 1716-30 * Intensify to a combination insulin regimen in year one if unacceptable hyperglycaemia 708 T2DM on dual OAD Add biphasic insulin twice a day Add prandial insulin three times a day R Year 1 Comparison of three single insulin regimens, added to OADs* Add basal insulin once (or twice) daily Add prandial insulin at midday Add basal insulin before bed Years 2 and 3 If HbA 1c >6.5%, stop sulfonylurea and add a second insulin formulation Add prandial insulin three times a day

27. Primary Outcome: HbA 1c at One Year N Engl J Med 2007; 357: 1716-30 — Biphasic — Prandial — Basal Mean ±SD at 1 year (%) 7.3±0.9 Baseline to 1 year (%) -1.3±1.1 7.2±0.9, p=0.08 vs. biphasic 7.6±1.0, p<0.001 vs. biphasic or prandial -0.8±1.0 -1.4±1.0 Months since randomisation Glycated haemoglobin (%) P<0.001

28. Glucose Profiles Before & After Starting Insulin — Biphasic — Prandial — Basal Change in FPG (mmol/l)) -2.5±3.1 Change in PPG (mmol/l) -3.8±3.5 - 1.3±2.7 -3.3±2.9 -2.6 ±3.0 -4.6±3.0 p<0.001 vs. biphasic p<0.001 vs. biphasic or prandial 0 — At baseline

29. Hypoglycaemia (≥ Grade 2) at One Year N Engl J Med 2007; 357: 1716-30 Months since randomisation Proportion with events (%) P=0.001 — Biphasic — Prandial — Basal Mean at 1 year (events/patient/year) 5.7 12.0, p<0.002 vs. biphasic 2.3, p=0.01 vs. biphasic, p<0.001 vs.prandial

33. Raskin P, Rojas P, Hu P et al. Comparison of twice-daily biphasic insulin aspart 70/30 (NovoLog Mix® 70/30) with once-daily insulin glargine in patients with type 2 DM on oral antidiabetic agents. Diabetes Care 2005; 28; 260-5.

34. 1530 Levemir® vs. NPH insulin Treat-to-target trial: Weight p<0.001 Hermansen K, et al., Diabetologia 2004;47(Supplement 1):A273

35. Baseline BMI 35 36 34 39 55 37 42 50 69 76 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 -0.5 Mean weight change (kg)  25 >25-27 >27-29 >29-31 >31 Insulin detemir NPH insulin 1530 Hermansen: Change in weight by baseline BMI K. Hermansen et al. EASD 2005

36. Type 1 effect of improved HbA1c

37. HbA 1c cross-sectional, median values

38. Any diabetes related endpoint M v I p=0.0034 overweight patients M v C p=0.0023