The MERIT™ Programme

1. The MERIT™ Programme Meeting Educational Requirements, Improving Treatment Pharmacy training: Helping people with type 2 diabetes to continue insulin therapy The MERITTM Programme was developed and is funded by Novo Nordisk

2. Training goals • On completion of this training, pharmacists will be able to: • Support people with diabetes who have recently taken responsibility for their own insulin therapy • Review the effectiveness of therapy in partnership with the individual and their partner, friend or carer

3. Agenda • Understanding diabetes • Goals of insulin therapy • Why insulin is needed • How insulin is used to control glucose • Supporting patients’ needs • Ideas for what you cover in a Medicines Use Review (MUR) • Injection technique and injection sites • Blood glucose monitoring • Insulin storage and sharps disposal • Sick day rules • Hypoglycaemia • Lifestyle advice • Typical problems and how to advise • Device workshop • Hands on!

4. The MERIT™ Programme Understanding diabetes

5. Diagnoses 75 g glucose 20 Venous plasma glucose (mmol/L) Diabetes • Type 1 diabetes • Type 2 diabetes • IGT (impaired glucose tolerance) • IFG (impaired fasting glucose) • GDM (gestational diabetes mellitus) • Other types of diabetes 15 IGT 11.1 mmol/L 10 7.8 mmol/L 5 0 0 30 60 90 120 Time after oral glucose (min) Diabetes diagnosis: Fasting plasma glucose ≥7.0 mmol/L OR 2 h plasma glucose ≥11.1 mmol/L Williams G, Pickup J. Handbook of Diabetes WHO. http://whqlibdoc.who.int/publications/2006/9241594934_eng.pdf (accessed Dec 2010)

6. Background to insulin therapy Goals of insulin therapy

7. Glycaemic control • Overall aim of insulin therapy: • To achieve near normal glycaemic control • Desired glycaemic control = blood glucose within the normal range: • Not too high • Not too low • Glycaemic control is measured using: • SMBG (self-monitored blood glucose) day-to-day readings • Laboratory assessments, e.g. HbA1c

8. Recommended glucose targets for patients with type 2 diabetes If a patient has been given Ketostix and blood glucose is >13 mmol/L, patient should test urine for ketones http://www.diabetes.org.uk/Documents/Professionals/primary_recs.pdf (accessed Dec 2010)http://www.diabetes.org.uk/About_us/Our_Views/Care_recommendations/Self-monitoring_of_blood_glucose/ (accessed Dec 2010http://www.diabetes.org.uk/Guide-to-diabetes/Monitoring/Blood_glucose/Urine_testing/ (accessed Dec 2010)http://www.nice.org.uk/nicemedia/pdf/CG87QuickRefGuide.pdf (accessed Dec 2010) http://www.diabetesuffolk.com/ManagingDiabetes/Sick%20day%20rules.htm (accessed Dec 2010)

9. Explaining HbA1c • What is HbA1c? • Over time, glucose in the blood slowly attaches to a chemical called haemoglobin in red blood cells Glycosylated haemoglobin or HbA1c • Once attached, the glucose will stay there for the life of the red blood cell, around 120 days • The more glucose that is attached, the higher the HbA1c level will be Owens D et al. Diabetes and Primary Care 2005;7:9–21

10. Explaining HbA1c • Why should HbA1c be measured? • HbA1c changes slowly so it provides an indication of the average glucose level in the preceding 2–3 months • HbA1c should complement, and not replace, self-monitored glucose readings • HbA1c should be measured every 2–6 months, until stable at desired level, and then 6 monthly (NCC-CC/NICE guidance) • Lowering HbA1c has been shown to reduce the development of eye, kidney and nerve disease NCC-CC, National Collaborating Centre for Chronic Conditions;NICE, National Institute for Health and Clinical Excellence http://www.nice.org.uk/Guidance/CG66/Guidance/pdf/English (accessed Dec 2010) Owens D et al. Diabetes and Primary Care 2005;7:9–21 Novo Nordisk. Raising HbA1c Awareness 2010

11. A new HbA1c assay A number of assays are available for measuring HbA1c Significant between-assay differences exist: Problems for patients Problems for clinical trials The IFCC have now synthesised a definitive international reference material New assay will provide results in mmol/mol IFCC, International Federation of Clinical Chemistry John WG et al. Clin Biochem Rev 2007;28:163–8

12. Relating the new and the old numbers Previous HbA1c(%) = (0.0915 × new IFCC result) + 2.15 Easy way to remember = “minus 2, minus 2” rule So if old HbA1c was 8: 8–2 = 6 6–2 = 4 New HbA1c = 64 DCCT, Diabetes Control Complications Trial Diabetes UK. HbA1c standardisation for clinical health care professionals. Available at: http://www.library.nhs.uk/Diabetes/ViewResource.aspx?resID=309817 (accessed Dec 2010)

13. Your turn! Using the –2,–2 rule, what is the new mmol/mol HbA1c for: 11%? 6%? 8%? 97 mmol/mol 11–2 = 9;9–2 = 7 42 mmol/mol 64 mmol/mol

14. Your turn! The –2,–2 rule only works for whole numbers Using the equation: What is the new mmol/mol HbA1c for: 6.5%? 7.9%? 8.7%? HbA1c(%) – 2.15 = new HbA1c (mmol/mol) 0.0915 48 mmol/mol 63 mmol/mol 72 mmol/mol

15. Background to insulin therapy Why is it important to control blood glucose?

16. 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 2006:111–2

17. Improving glucose control reduces risk Lowering HbA1c† by 1% (11 mmol/mol) significantly reduces: –14%* Reduction in incidence risk per 1% reduction in HbA1c –21%* –37%* –43%* †HbA1c (glycosylated haemoglobin) provides an average measure of blood glucose in the past 2–3 months *p<0.0001 Stratton IM et al. BMJ 2000;321:405–12

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

19. Conclusion • Achieving a target HbA1c of 6.5–7.5% (48–58 mmol/mol) is important • Improved glycaemic control reduces the risk of complications NICE Guidelines – Managing Type 2 Diabetes, managing blood glucose control. http://www.nice.org.uk/guidance/index.jsp?action=byID&o=11983 (accessed Dec 2010)

20. Background to insulin therapy Why is insulin treatment needed?

21. 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, DPP-4 inhibitors (or glitazone) Step 2. Oral antidiabetic agents E.g. metformin plus sulphonylurea, metformin plus glitazone, metformin plus DPP-4 inhibitors, metformin plus GLP-1 receptor agonists Step 3. Polytherapy INSULIN With/without oral agent Recent guidelines suggest insulin should be used earlier2,3 DPP-4, dipeptidyl peptidase-4; GLP-1, glucagon-like peptide 1 1. Bergenstal RM et al. In: Degroot LJ, Jameson J (eds). Endocrinology 2001: 821–35 2. Nathan DM et al. Diabetes Care 2006;29:1963–723. ADA American Diabetes Association. Diabetes Care 2008;31:12–54

22. Most people with type 2 diabetes will, in time, need insulin therapy 60 Patients requiring additional insulin (%) 50 40 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? UKPDS, United Kingdom Prospective Diabetes Study Wright A et al. Diabetes Care 2002;25:330–6

23. Background to insulin therapy How is insulin used to control glucose?

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

25. Human insulins Humulin® S, Humulin® I and Humulin® M3 are registered trademarks of Eli Lilly and Company;Insuman® Rapid, Insuman® Basal and Insuman® Comb are registered trademarks of sanofi-aventis;Actrapid® and Insulatard® are registered trademarks of Novo Nordisk

26. Insulin analogues Humalog® is a registered trademark of Eli Lilly and Company;Lantus® and Apidra® are registered trademarks of sanofi-aventis;NovoRapid®, NovoMix® and Levemir® are registered trademarks of Novo Nordisk

27. What are insulin analogues? -chain • Insulin analogues are formed by modifying human insulin molecules • Like soluble human insulin, insulin analogues 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

28. Benefits of insulin analogues 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 Hirsch IB. N Engl J Med 2005;352:174–83Lindholm A. Best Pract Res Clin Gastroenterol 2002;16:475–92

29. Different types of insulin can be combined into different regimens • Possible insulin regimens include: • Once-/twice-daily intermediate- or long-acting (basal) insulin • Once-/twice-/three-times-daily premixed insulin • Basal–bolus therapy • Mealtime short-acting insulin

30. Once-daily basal insulin • Exact duration depends on the insulin type and dose • Basal insulin analogues may provide up to 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 insulin analogue Insulinaction Insulin injection Time Schematic representation

31. 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 (accessed Dec 2010)

32. Premixed insulin – once-, twice- or three-times-daily Premixed human insulin Premixed insulin analogue 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 (only biphasic insulin aspart) Insulinaction Breakfast Lunch Dinner Schematic representation of twice-daily injections

33. 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 *Although most patients are started on twice-daily premixed regimens 1. Garber AJ et al. Diabetes Obes Metab 2006;8:58–66

34. Basal–bolus therapy Short-acting human insulin Rapid-acting insulin analogue Long-acting insulin analogue Intermediate-acting human insulin Rapid insulin Rapid insulin Rapid insulin Longinsulin Insulinaction Breakfast Lunch Dinner Bedtime Schematic representation of four injections per day (one long-acting, three rapid-acting)

35. Benefits of a basal–bolus insulin regimen • This regimen produces an insulin profile that is closest to natural insulin production by the body • Offers greater flexibility over type of food and when it can be eaten • Suited to those who are highly motivated

36. 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 • Sitagliptin was approved for use with insulin in the EU in November 2009 EU, European Union http://www.nice.org.uk/Guidance/CG66/Guidance/pdf/English (accessed Dec 2010)

37. Key summary points • Different insulins can be combined into different regimens • Different insulin regimens, types of insulin and insulin devices are available

38. Supporting patients who are using insulin via an MUR Support needs MUR, Medicines use review

39. MUR checklistPt Name: CHI Number:

40. Why do patients need support? • Insulin treatment requires continuous commitment: • Often several injections a day • No time off • Insulin treatment will be successful only if the patient is: • Educated • Motivated • Empowered • Patients need to know when to inject, what to inject and how to inject Support from you, family and friends is essential to optimise self-management Diabetes UK http://www.diabetes.org.uk/Documents/Professionals/primary_recs.pdf (accessed Dec 2010)

41. Support at insulin initiation • At initiation, patients should have received detailed information on: • Injection techniques • Practicalities (e.g. insulin storage, needle disposal, informing authorities) • Blood glucose monitoring • And are likely to have received basic information on: • Hypoglycaemia • Diet • Exercise • Weight gain • Sick day rules • A MUR provides the opportunity to check a patient’s knowledge and understanding and to ensure they are taking their insulin appropriately Royal College of Nursing. http://www.rcn.org.uk/__data/assets/pdf_file/0009/78606/002254.pdf (accessed Dec 2010)

42. Injection technique • Insert the needle at ~90° • Push needleall the way in • Push the buttonto inject the insulin • Leave the needlein place for 10 seconds • Remove the needle • If required, pinch skin before inserting the needle: • Squeeze skin between your thumb and two fingers • Insert the needle • Hold the pinch • Inject the insulin • Leave the needlein place for a count of 10 seconds • Releaseyour grip on skin • Remove the needle • Getting the ‘pinch up’ right Correct Incorrect Needle insertion Royal College of Nursing. http://www.rcn.org.uk/__data/assets/pdf_file/0009/78606/002254.pdf (accessed Dec 2010) The Forum for Injection Technique (FIT). The First UK Injection Technique Recommendations. Oct 2010

43. Injection sites • Insulin should be injected into subcutaneous fat • Several injection sites can be used: • Abdomen • Back of arms • Thighs • Buttocks • Insulin should not be injected through clothing Fastest absorption Slowest absorption The Forum for Injection Technique (FIT). The First UK Injection Technique Recommendations. Oct 2010

44. Needles are available in different lengths • Choosing the right length is important to reduce risk of intramuscular injections • No clinical reason to use needles >8 mm • All diabetes patients can use 4, 5 and 6 mm needles regardless of BMI • Shorter needles are less likely to require ‘pinch up’ BMI, body mass index The Forum for Injection Technique (FIT). The First UK Injection Technique Recommendations. Oct 2010

45. Needle management It is recommended that needles are used only once After use, they should be detached from the device and disposed of in a sharps bin Under no circumstances should a HCP re-sheath a needle HCP, healthcare professional Royal College of Nursing.http://www.rcn.org.uk/__data/assets/pdf_file/0009/78606/002254.pdf (accessed Dec 2010) The Forum for Injection Technique (FIT). The First UK Injection Technique Recommendations. Oct 2010

46. Needle re-use issues Can cause increased pain if blunt Can bend or break Non-sterile – increased risk of infections Crystallisation of old insulin in the needle bore may block needle leading to altered insulin flow New needle Used needle • Change in insulin concentration due to leakage of insulin through the needle • Air can enter the insulin reservoir through the needle, which can make the pen malfunction • Reusing needles can increase the number of complaints regarding needles and devices Royal College of Nursing.http://www.rcn.org.uk/__data/assets/pdf_file/0009/78606/002254.pdf (accessed Dec 2010) The Forum for Injection Technique (FIT). The First UK Injection Technique Recommendations. Oct 2010

47. Resuspending insulin • Cloudy insulin preparations need resuspending before use: • E.g., NPH insulin, premixed insulin • Clear insulins do not need resuspending: • E.g. insulin detemir (Levemir®), insulin glargine (Lantus®) • Resuspension should be performed before any of the other actions • If resuspension is required, gently roll and invert the pen in your hands at least 10 times until the crystals go back into suspension NPH, neutral protamine Hagedorn The Forum for Injection Technique (FIT). The First UK Injection Technique Recommendations. Oct 2010

48. Performing air-shots (priming) A two unit air-shot should be performed before each injection Check dose setting is at 0 and dial 2 units • Point device upwards (needle to ceiling) and tap gently with finger • Push button and a drop of insulin should appear at tip of needle

49. The importance of self-monitoring blood glucose • Monitoring glucose is importantfor safe and successful insulin treatment: • It guides dose adjustment • It allows patients to see the impact of behaviours and diet on glucose • Identify patients using old meters and inform them about the benefits of new meters • You should ensure that patients know how to monitor glucose • The most important aspect of self-monitoring is that the patients use the results Diabetes UK. http://www.diabetes.org.uk/Documents/Professionals/primary_recs.pdf (accessed Dec 2010) http://www.nice.org.uk/Guidance/CG66/Guidance/pdf/English. (accessed Dec 2010) Owens D et al. Diabetes and Primary Care 2004;6:8–16

50. When to take blood for testing Owens D et al. Diabetes and Primary Care 2004;6:8–16 Owens D et al. Diabetes and Primary Care 2005;7:9–21 Diabetes UK, http://www.diabetes.org.uk/About_us/Our_Views/Care_recommendations/Self-monitoring_of_blood_glucose/ (accessed Dec 2010)