1. Company Confidential © 2012 Eli Lilly and Company Prescribing human insulin: What do the guidelines say and what does this mean in practice? Speaker name and affiliation Prescribing information is available on the last slide. © 2013 Eli Lilly and Company UKDBT01519b September 2013

2. Company Confidential © 2012 Eli Lilly and Company © 2013 Eli Lilly and Company This session will discuss:  NICE (and SIGN) guideline regarding human NPH insulin prescribing in type 2 diabetes  What does NICE (and SIGN) recommend regarding use of pre-mixed human insulin in type 2 diabetes?  The health economics of the situation and the impact of the QIPP agenda  Discussion of the local situation regarding prescribing human NPH insulin 2 NPH=neutral protamine Hagedorn; QIPP=Quality, Innovation, Productivity and Prevention

3. What does NICE say about initiating insulin in type 2 diabetes? Section subhead copy here if needed or section presenter info

4. Company Confidential © 2012 Eli Lilly and Company © 2013 Eli Lilly and Company Starting insulin therapy in type 2 diabetes: NICE advice (2009) 4 NPH=neutral protamine Hagedorn NICE. Type 2 diabetes: newer agents for blood glucose control in type 2 diabetes. CG87. London: NICE; May 2009. www.nice.org.ukwww.nice.org.uk Begin with human NPH insulin injected at bedtime or twice daily according to need.  If other measures do not keep HbA 1c <58 mmol/mol (<7.5%; or other agreed target), discuss the benefits and risks of insulin treatment Alternatively, consider a once-daily long-acting insulin analogue (insulin detemir, insulin glargine) if The person needs help with injecting insulin and a long-acting insulin analogue would reduce injections from twice to once daily, or The person’s lifestyle is restricted by recurrent symptomatic hypoglycaemic episodes, or The person would otherwise need twice-daily NPH insulin injections plus oral glucose lowering drugs, or The person cannot use the device to inject NPH insulin.

5. Company Confidential © 2012 Eli Lilly and Company © 2013 Eli Lilly and Company Starting insulin therapy in type 2 diabetes: NICE advice (2009) 5 NICE. Type 2 diabetes: newer agents for blood glucose control in type 2 diabetes. CG87. London: NICE; May 2009. www.nice.org.ukwww.nice.org.uk Consider twice-daily biphasic human insulin (pre-mixed) (particularly if HbA 1c ≥75mmol/mol [≥9%]) A once-daily regimen may be an option. Consider pre-mixed preparations of insulin analogues (including short-acting insulin analogues) rather than pre-mixed human insulin preparations if: Immediate injection before a meal is preferred, or Hypoglycaemia is a problem, or Blood glucose levels rise markedly after meals.  If other measures do not keep HbA 1c <58 mmol/mol (<7.5%; or other agreed target), discuss the benefits and risks of insulin treatment

6. What does SIGN say about initiating insulin in type 2 diabetes? Section subhead copy here if needed or section presenter info

7. Company Confidential © 2012 Eli Lilly and Company © 2013 Eli Lilly and Company Starting insulin: SIGN advice 7 NPH=neutral protamine Hagedorn SIGN. Management of diabetes. 116. March 2010. www.sign.ac.ukwww.sign.ac.uk  When commencing insulin therapy, bed-time basal insulin should be initiated and the dose titrated against morning (fasting) glucose. If the HbA 1c level does not reach target then addition of prandial insulin should be considered  A once daily bed-time human NPH insulin should be used when adding insulin to metformin and/or sulphonylurea therapy. Basal insulin analogues should be considered if there are concerns regarding hypoglycaemia risk  A soluble human insulin or rapid-acting insulin analogues can be used when intensifying insulin regimens to improve or maintain glycaemic control

8. Insulin prescribing: Health economics considerations Section subhead copy here if needed or section presenter info

9. Company Confidential © 2012 Eli Lilly and Company © 2013 Eli Lilly and Company The financial cost of diabetes 9 Hex N et al (2012) Diabet Med 29: 855–62 Overall 2010/2011 cost £23.7bn Direct costs £9.8bn Type 2 direct costs £8.8bn Type 1 direct costs £1.0bn Indirect costs £13.9bn Type 2 indirect costs £13.0bn Type 1 indirect costs £0.9bn  “…the estimate that the cost of diabetes accounts for approximately one tenth of NHS expenditure is accurate.”  “…less than a quarter of that cost relates to the treatment and ongoing management of diabetes, with the rest being accounted for by the costs of treating the complications of diabetes.”

10. Company Confidential © 2012 Eli Lilly and Company © 2013 Eli Lilly and Company Between 1997 and 2007, expenditure on diabetes therapies increased 10 Currie CJ et al (2010) Diabetic Medicine 27: 938–48  Retrospective study in the UK from 1997 to 2007  n=126,052: 11,300 (8.9%) with type 1 diabetes; 114,752 (91.1%) with type 2 diabetes  Expenditure on type 2 diabetes (per person per year):

11. Company Confidential © 2012 Eli Lilly and Company © 2013 Eli Lilly and Company Has the increasing expenditure on diabetes therapies improved glycaemic control? 11 Currie CJ et al (2010) Diabetic Medicine 27: 938–48  Retrospective study in the UK from 1997 to 2007  n=126,052: 11,300 (8.9%) with type 1 diabetes; 114,752 (91.1%) with type 2 diabetes  Expenditure on type 2 diabetes (per person per year): However, over the 10 year period, the mean HbA 1c values did not improve at all!

12. Company Confidential © 2012 Eli Lilly and Company © 2013 Eli Lilly and Company The cost of basal insulin preparations in 2013 12 Insulin analogues have become increasingly popular despite their greater cost compared with human insulin 1 Examples of comparative costs of human and analogue insulins 2 £72* £42 £41.50 £22.90 £19.08£17.50 £72* £42 £41.50 £21.70 £20.40£19.80 *Relates to the 100 unit/mL preparations; a 200 unit/mL preparation is also available at a cost of £86.40 for a 3 x 3mL prefilled pen 1. Holden SE et al (2011) BMJ Open 1: e000258 2. MIMS Online (2013) Insulins. Available at: http://www.mims.co.uk/Drugs/diabetes/insulins (accessed 19.03.2013)http://www.mims.co.uk/Drugs/diabetes/insulins

13. Company Confidential © 2012 Eli Lilly and Company © 2013 Eli Lilly and Company UK NHS spend on basal insulins during 2012 (IMS data) 1 13  Only 8.3% of the basal insulin spend nationally is on human NPH insulin 1  If all prescriptions dispensed for analogue insulin between 2000 and 2009 had used a human insulin alternative, the NHS would have saved an estimated £625 million 2 NPH=neutral protamine Hagedorn 1. DATA ON FILE: UK NHS spend on basal insulins during 2012 2. Holden SE et al (2011) BMJ Open 1: e000258 )

14. Company Confidential © 2012 Eli Lilly and Company © 2013 Eli Lilly and Company Quality, Innovation, Productivity and Prevention (QIPP) 14 1.NHS Improvement (2013) QIPP - Resources. Available at: http://bit.ly/d0aQqk (accessed 08.04.2013)http://bit.ly/d0aQqk 2.NICE (2013) Key therapeutic topics – Medicines management options for local implementation. Available at: http://bit.ly/11nsJ4r (accessed 08.04.2013)http://bit.ly/11nsJ4r  QIPP is a national Department of Health strategy for the NHS, involving all NHS staff, clinicians, patients and the voluntary sector. It aims to improve the quality and delivery of NHS care whilst reducing costs to make £20 billion of efficiency savings by 2014–15. These savings will be reinvested to support the front line. 1  In terms of long-acting and intermediate-acting insulins, QIPP states: “Review and, if appropriate, revise prescribing of long- acting insulin analogues for type 2 diabetes mellitus to ensure that it is in line with NICE guidance” 2

15. Company Confidential © 2012 Eli Lilly and Company © 2013 Eli Lilly and Company NICE: QIPP Key therapeutic topics Medicines management options for local implementation 15 Long-acting insulin analogues:  The net ingredient cost of all insulin therapy in primary care in 2011/12 was £314.7 million; a growth of 42.5% from 2005/6. – In 2011, 1.3 million items of insulin glargine were prescribed at a cost of just over £77 million, and just over 600,000 items of insulin detemir at a cost of nearly £40 million – This compared with nearly 350,000 items of NPH (isophane) insulin at a cost of just over £12 million  In most PCTs more than 80% of all intermediate or long-acting insulin items (excluding biphasic insulins) were for insulin glargine or insulin detemir  However, the trend of increased preference for prescribing long or intermediate-acting insulin analogues over other types has recently reversed NICE (2013) Key therapeutic topics – Medicines management options for local implementation. Available at: http://bit.ly/11nsJ4r (accessed 19.03.2013)http://bit.ly/11nsJ4r

16. Company Confidential © 2012 Eli Lilly and Company © 2013 Eli Lilly and Company Variation in the percentage of long-acting insulin analogues prescribed across PCTs 16 PCT=Primary Care Trust NICE (2012) Cardiovascular – type 2 diabetes Data focused commentary: Type 2 diabetes: long-acting insulin analogues. Available at: http://bit.ly/XWr57r (accessed 19.03.2013)http://bit.ly/XWr57r  Across PCTs, long-acting insulin analogues make up between 36– 98% of the prescribing of all long- and intermediate-acting insulins (excluding biphasics)  In the majority of PCTs, more than 80% of all intermediate or long- acting insulin items (excluding biphasic insulins) are long-acting insulin analogues and in many PCTs the proportion is more than 90%  Therefore, in many PCTs, only 10% of all intermediate or long-acting insulin items prescribed are for human NPH insulin

17. Company Confidential © 2012 Eli Lilly and Company © 2013 Eli Lilly and Company Let’s discuss 17  How much do you think you are spending on prescribing basal insulins in your locality?

18. Company Confidential © 2012 Eli Lilly and Company © 2013 Eli Lilly and Company Local insulin prescribing costs 18  >

19. Local guidelines regarding the prescribing of insulin in type 2 diabetes Section subhead copy here if needed or section presenter info

20. Company Confidential © 2012 Eli Lilly and Company © 2013 Eli Lilly and Company Let’s discuss 20  What do your local guidelines recommend regarding the prescribing of insulin in type 2 diabetes?

21. Company Confidential © 2012 Eli Lilly and Company © 2013 Eli Lilly and Company Local guidelines for insulin prescribing 21  >

22. Company Confidential © 2012 Eli Lilly and Company © 2013 Eli Lilly and Company Session 2 summary 22  National guidelines recommend initiating insulin for people with type 2 diabetes by using human NPH insulin  National guidelines suggest that long-acting insulin analogues are considered as options in specific circumstances  Insulin analogues have come under increasing scrutiny due to their widespread use and greater cost compared with human NPH insulin – In England, the QIPP agenda is encouraging cost savings in diabetes, and insulin prescribing is one area of focus NPH=neutral protamine Hagedorn; QIPP=Quality, Innovation, Productivity and Prevention

23. UKDBT01519b September 2013