The MERIT™ Programme

1. The MERIT™ Programme Meeting Educational Requirements, Improving Treatment Module 2: Helping people with type 2 diabetes to continue insulin therapy The MERITTM Programme was developed and is funded by Novo Nordisk. Prescribing information can be found at the end of this slide kit.

2. Course overview • How the MERIT Programme will help you • Module 2: Helping people with type 2 diabetes to continue insulin therapy • Initial support • Reviewing progress

3. Section 1: The MERIT Programme 1.1 Why was the MERIT Programme developed?

4. The Skills for Health Diabetes Competency Framework • MERIT is based on Skills for Health • Skills for Health is supported by the Department of Health • It aims to develop the health workforce in the UK including those treating diabetes patients • Outlines skills and knowledge needed to treat diabetes • Aims to improve diabetes care • Overall focus: ‘What does the person with diabetes need?’ http://www.skillsforhealth.org.uk/tools/view_framework.php?id=110

5. How is the framework relevant to you? • The Diabetes Competency Framework is aimed at all healthcare professionals who are involved in diabetes care Secondary care Primary care Patient • Many elements of diabetes care are provided in primary care • Primary care will become increasingly important as the prevalence of diabetes increases

6. The MERIT Programme involves several ‘pick and mix’ modules

7. General notes • The information in the MERIT Programme should be used in conjunction with prescribing information • Prescribing information is available for all products mentioned • Please consult your sales representative or tutor • MERIT has been developed by, and is the property of, Novo Nordisk. It is illegal to use any of the contents of the MERIT Programme without the prior permission of Novo Nordisk

8. Section 1: The MERIT Programme 1.2 Overview of Module 2

9. Module 2: Helping people with type 2 diabetes to continue insulin therapy • Based around competency Diab_HD3 of the competency framework:‘Supporting a person with type 2 diabetes who has recently started an insulin regimen’ • On completion of this module, you will have the necessary information to be able to: • Support people with type 2 diabetes who have recently taken responsibility for their own insulintherapy • Review and evaluate the effectiveness of therapy in partnership with the individual and their carer

10. You have already completed a competency assessment form Reassess competencies after MERIT module Prioritise six areas for additional training Clinical mentor will work with you on these competence priorities Competency Assessment Form Turns theoryinto practice

11. Helping people with type 2 diabetes to continue insulin therapy: course overview • Background to insulin therapy • Why we need insulin • How insulin is used • Support needs • Initial support • Ongoing support • Recording and reviewing progress

12. Section 2: Background to insulin therapy 2.1 Goals of insulin therapy

13. Glucose control • Overall aim of insulin therapy: • To achieve near-normal glucose control (normoglycaemia) • Blood glucose not too high, nor too low • Glucose control is measured using: • Day-to-day blood readings • Laboratory assessments, e.g., HbA1c

14. Section 2: Background to insulin therapy 2.2 Why is it important to control blood glucose?

15. Poor glucose control is associated with increased risk of complications Stroke Retinopathy and blindness Heart disease Kidney disease Erectile dysfunction Neuropathy Peripheral vascular disease Diabetic foot disease Diabetes is a serious condition; there is no such thing as ‘mild diabetes’ or a ‘touch of diabetes’ International Diabetes Federation. Diabetes Atlas,2006

16. Patients with type 2 diabetes are at increased risk of cardiovascular disease • Risk of cardiovascular disease is greater in patients with diabetes than in those without • Having diabetes results in a similar risk of heart attack as a prior heart attack Incidence of myocardial infarction (%) over 7 years (n = 1373) (n = 1059) Haffner SM et al. N Engl J Med 1998;339:229–34

17. Risk of complications increases as HbA1c increases Microvascular disease Incidence per1000 patient-years Myocardial infarction Updated mean HbA1c (%) Stratton IM et al. BMJ 2000;321:405–12

18. Reducing HbA1c reduces risk Lowering HbA1c by 1% significantly reduces: –14%* Reduction in incidence risk per 1% reduction in HbA1c –21%* –37%* –43%* *p<0.0001 Stratton IM et al. BMJ 2000;321:405–12

19. Postprandial glucose is an independent risk factor for mortality Incidence(rate per 1000) Borderline (≤10 mmol/l) Poor (>10 mmol/l) Good (4.4–8.0 mmol/l) Postprandial glucose control Hanefeld M et al. Diabetologia 1996;39:1577–83

20. Why does elevated glucose cause complications? Blood glucose/ prolonged hyperglycaemia Oxidative stress Impaired cardiovascular regulation Structural changes to vessels Insulin resistance and beta-cell failure Brownlee M. Nature 2001;414:813–20 Del Prato S. Int J Obes Rel Metab Disord 2002;26(Suppl 3):S1–9 Evans JL et al. Diabetes 2003;52:1–8; Haller H. Diabetes Res Clin Pract 1998;40(Suppl):S43–9

21. Glucose control should occur alongside control of other cardiovascular risk factors Elevated blood glucose Dyslipidaemia Cardiovascular risk factors Excess body weight High blood pressure Smoking Turner RC et al. BMJ 1998;316:823–8

22. Key summary points • Improved glycaemic control reduces the risk of complications • Control of mealtime glucose as well as fasting glucose is important • Glucose control should occur alongside management of other CV risk factors

23. Section 2: Background to insulin therapy 2.3 Why is insulin treatment needed?

24. Onset 250 Insulin resistance 200 150 Beta-cell function (%) Normal 100 50 Insulin secretion 0 –10 –5 0 5 10 15 20 25 Type 2 diabetes is characterised by progressive loss of insulin secretion Years of diabetes Bergenstal RM et al. In: Degroot LJ, Jameson J (eds). Endocrinology 2001;821–35

25. Onset 21 Post-meal glucose (postprandial) 18 15 Fasting glucose Plasma glucose (mmol/l) 12 9 Normal 6 3 0 –10 –5 0 5 10 15 20 25 As beta-cells fail, both postprandial and fasting glucose control deteriorate Years of diabetes Bergenstal RM et al. In: Degroot LJ, Jameson J (eds). Endocrinology 2001;821–35

26. Glucose control deteriorates over time even with oral drug treatment Glibenclamide 9 Chlorpropamide 8 Metformin Recommended target ≤ 6.5%† 7 6 Typical HbA1cin people without diabetes 5 Median HbA1c (%) 4 3 2 1 0 0 2 4 6 8 10 Years from randomisation †Diabetes UK and NICE guidelines. http://www.diabetes.org.uk/Documents/Professionals/primary_recs.pdfNICE. http://www.nice.org.uk/nicemedia/pdf/NICE_full_blood_glucose.pdf UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854–65

27. Insulin is often needed • It is important to maintain good glycaemic control: • Not just HbA1c; controlling mealtime glucose is also important • Type 2 diabetes is a progressive disease • Over time, oral agents become less effective at achieving targets Need for insulin treatment

28. Most people with type 2 diabetes will, in time, need insulin therapy 60 50 40 Patients requiring additional insulin (%) 30 20 10 0 1 2 3 4 5 6 Years from start of UKPDS (Patients treated with chlorpropramide) Should more of our patients be using insulin? Wright A et al. Diabetes Care 2002;25:330–6

29. Traditionally, insulin is used only when oral agents fail to control glucose Step 1. Lifestyle changes E.g. diet and exercise E.g. metformin, sulphonylurea (or glitazone) Step 2. Oral antidiabetic agents E.g. metformin plus sulphonylurea, metformin plus glitazone Step 3. Oral polytherapy INSULIN With/without oral agent Bergenstal RM et al. In: Degroot LJ, Jameson J (eds). Endocrinology 2001: 821–35 2. Nathan DM et al. Diabetes Care 2006;29:1963–72 3. AACE Guidelines. Endocr Pract 2007;13(Suppl 1):1–66

30. Section 2: Background to insulin therapy 2.4 How is insulin used to control glucose?

31. How insulin works Food intake* Insulin released from Pancreas Increased plasma insulin stimulates: Liver: Glucose uptake and glycogen synthesis Muscles:Glucose uptake and glycogen synthesis Adipose tissue (fat): Glucose uptake Controlled blood glucose *or rising blood glucose due to other events such as glycogen breakdown

32. Consequences of no insulin • Without insulin, glucose is not taken up by cells Elevated blood glucose after and between meals

33. Insulin treatment attempts to mimic the pattern of normal insulin secretion Short-lived, rapidly generated meal-related insulin peaks 70 60 50 40 Insulin (µU/ml) Low, steady, basal insulin profile 30 20 10 0 6:00 10:00 14:00 18:00 22:00 2:00 6:00 Time of day Polonsky KS et al. J Clin Invest 1988;81:442–8

34. Mealtime glucose is a significant contributor to overall glucose control • Mealtime glucose accounts for 30–70% of HbA1c • The contribution of mealtime glucose to HbA1c increases as control improves 100 80 Fasting glucose 60 Contribution to HbA1c (%) 40 Mealtime glucose 20 0 <7.3 7.3–8.4 8.5 –9.2 9.3 –10.2 >10.2 HbA1c Monnier L et al. Diabetes Care 2003;26:881–5

35. There are different types of insulin regimen • When trying to recreate the normal pattern of insulin secretion, different patients have different needs • Therefore, different regimens are available. These differ: • In the number of injections involved • In the type of insulin used

36. The development of insulin • Animal insulin (discovered 1921, now rarely used) • Human insulin (introduced 1980s) • Analogue insulin (introduced 1990s, sometimes referred to as “modern insulins”) Insulin analogues are introduced Animal insulin commercially available Two major types of diabetes defined: type 1 and type 2 Use of animal insulin first tested with success on a 14-year-old boy Commercial production of human insulin 1920 1930 1940 1950 1960 1970 1980 1990 2000 Gualandi-Signorini AM, Giorgi G. Eur Rev Med Pharmacol Sci 2001;5:73–83 Lindholm A. Best Pract Res Clin Gastroenterol 2002;16:475–92 Gale EAM. Diabetes 2001;50:217–26

37. Types of insulin • Animal insulin (Used since 1922) • Short acting • Intermediate acting • Mixture of short and intermediate acting (biphasic) • Human insulin (Since 1982) • Short acting • Intermediate acting • Mixture of short and intermediate acting (biphasic) • Analogue insulin (Since 1996) • Rapid acting • Long acting (basal insulin) • Mixture of rapid and intermediate acting (biphasic)

38. What are analogue insulins? -chain • Analogue (or modern) insulins are formed by modifying human insulin molecules • Like soluble human insulin, analogue insulins are produced by recombinant DNA technology Gly s s -chain Ala Cys Phe s Thr s Lys s Pro s Insulin lispro -chain Gly s s -chain Ala Cys Phe s Thr s Lys Asp Pro s s Insulin aspart Hirsch IB. N Engl J Med 2005;352:174–83

39. Why do we need analogue insulins? Shortfalls of short-acting human insulins • Short-acting insulin time–action profiles are not ideal: • Should be injected up to 30 minutes before a meal • Slow absorption, not a physiological profile • Duration of action can last up to 8 hours • Increased risk of hypoglycaemia compared with analogue insulins Heller S et al. Diabetes Res Clin Pract 2007;78(2);149–58

40. Why do we need analogue insulins? Shortfalls of long-acting human insulins • Intermediate-acting insulin time–action profiles are not ideal: • Insulin peaks during the night, increasing the risk of nocturnal hypoglycaemia • After peak, action not sustained for 24 hours • Low predictability and day-to-day variation in absorption rate • Inadequate re-suspension is a potential source of error in some formulations

41. Human insulins Humulin S and Humulin I are registered trademarks of Eli Lilly and CompanyInsuman Rapid, Insuman Basal, and Insuman Comb are registered trademarks of Sanofi-AventisInsulatard and Mixtard 30 are registered trademarks of Novo Nordisk

42. Analogue insulins Humalog is a registered trademark of Eli Lilly and CompanyLantus and Apidra are registered trademarks of Sanofi-AventisNovoRapid, NovoMix and Levemir are registered trademarks of Novo Nordisk

43. Benefits of analogue over human insulins • Fewer hypoglycaemic events • May improve glycaemic profile • Offer greater lifestyle flexibility • Rapid-acting analogues can be injected just before, just after or during a meal • Easy to omit if not eating (rapid only) Hirsch IB. N Engl J Med 2005;352:174–83Lindholm A. Best Pract Res Clin Gastroenterol 2002;16:475–92

44. Types of insulin regimens • Once-daily/twice-daily intermediate- or long-acting (basal) insulin • Once-/twice-/three-times daily premixed insulin • Basal–bolus therapy • Mealtime rapid-acting insulin

45. Insulin with or without oral agents? • The majority of insulins are licensed with oral drugs • Metformin should be continued wherever possible • Sulphonylureas can be used with insulin • In February 2007, pioglitazone was indicated for use with insulin in the UK • Concerns over fluid retention and heart failure NICE http://www.nice.org.uk/nicemedia/pdf/NICE_full_blood_glucose.pdf Royal College of Nursing. http://www.rcn.org.uk/__data/assets/pdf_file/0009/78606/002254.pdf

46. Once-daily basal insulin • Exact duration depends on the insulin • Insulin analogues may provide 24-hour cover • Intermediate human insulin preparations may only be active for ~8 hours and have a more pronounced peak activity basal human insulin basal analogue insulin Insulinaction Insulin injection Time Schematic representation

47. Benefits of a once-daily basal insulin regimen • Requires only one injection per day • May help overcome resistance to starting insulin injections • Particularly useful when patient’s blood glucose is high overnight and in the morning • Useful for patients who require someone else (e.g., a district nurse) to administer their insulin • May be associated with fewer side effects than other regimens1 1. Holman RR et al. N Engl J Med 2007;357:1716-30 Royal College of Nursing. http://www.rcn.org.uk/__data/assets/pdf_file/0009/78606/002254.pdf

48. Limitations of once-daily basal insulin regimen • Does not provide insulin specifically for post-meal glucose surges: • Assumes patient can produce sufficient insulin to cover these mealtime requirements • Requires a fairly strict, predictable diet: • Dosing during the day is inflexible and so patients need to consume similar calories each day

49. Premixed insulin – once, twice or three-times daily Premixed human insulin Premixed analogue insulin Premixed injection Premixed injection Contains: • Basal component • Short-acting component Possible regimens: • Once daily with largest daily meal (usually dinner) • Twice daily with dinner and breakfast (figure) • Three-times daily, with each meal Insulinaction Breakfast Lunch Dinner Schematic representation of twice-daily injections

50. Benefits of a premixed insulin regimen • Targets mealtime glucose • Suited to people with fairly regular lifestyles, who eat similar amounts at similar times each day • Can be initiated as one injection per day to familiarise patient with injecting* • Second or third injections of same insulin in same device can be added if necessary to optimise control1 1. Garber AJ et al. Diabetes Obes Metab 2006;8:58–66 *although most patients are started on twice-daily premixed regimens