NICE Update December 09

1. NICE Update December 09 • Nemanja Stojanović FRCP • Consultant Endocrinologist, Queen’s Hospital Romford

2. We Will Discuss • NICE Guidance 2008 & 9 • Glycaemic Targets • All classes of Drugs that are used as 2nd or 3rd line treatments • Evidence behind the new classes of drugs • NICE guidance update • Cholesterol Targets/ BP Targets • NICE updated Guidelines 2009

3. Definition • Fasting plasma glucose 7mmol/l- 2 occasions • 2 h plasma glucose or random glucose of 11.1 mmol/l

4. NICE Guidance: General Points

5. NICE 08 & 09 • Patient centered care • Good communication is essential • Support the care with evidence based medical information • Allow patient is to reach informed decisions about their care • Information “ Culturally appropriate”

6. Education • Meet the national criteria laid down by DoH • Meet the local cultural, linguistic, cognitive and literacy needs • Provide appropriate resources to support the educators, who should be properly trained and allowed time to develop and maintain their skills.

7. Target HbA1c • Patients on Monotherapy 6.5% • Patients on multiple medications or Insulin 7.5% • Escalate treatment when HbA1c is> 7.5%

8. HbA1c and Mean Glucose Dia Care 31:1473–1478, 2008

9. Times of Plenty: Type 2 Diabetes • Prevalence 3.7% England & 4.2% Wales = 2,000,000 people • > 85% T2DM • At least 5% of the UK healthcare Expenditure • 10%of hospital budget in the UK...

10. Possible Second Line Treatments Spoilt for choice?? We have to make one!! • Sulfonylureas (Not Glibenclamide) • PPG’s (Postprandial Glucose Regulators) • TZDs • DPP- 4 Inhibitors • GLP-1 Analogues • α glucosidaze inhibitors • Insulin

11. Sulfonylureas

12. SU’s and Glycaemic Control • Major Effects • Decrease FPG~3mmol/l • Decrease A1c 1-2% • Weight gain 3-4kg • Hypoglycaemia: fasting or late postprandial • Minor Effects • Meal mediated insulin secretion • Postprandial glucose excursions

13. University Group Diabetes Program (UGDP) • USA: late 1960’s • Comparison between Diet, Insulin and OHA’s • Study of natural history of vascular disease in T2DM • Development of appropriate methods for cooperative clinical trials • Excess mortality in tolbutamide subgroup Diabetes 1976;25: 1129-53 ©EndoDiabetes.com

14. GLP-1 Axis Medications: GLP-1 Analogues and DPP-4 Inhibitors

15. GLP-1 • Gut derived incretin hormone: L cells • Augments glucose dependent insulin secretion • Supports the synthesis of proinsulin • In vitro/ rodents • Reduces the rate of β cell apoptosis in a toxic environment • Promotes β cell differentiation from the precursor cells

16. DPP-4 inhibitors/ GLP 1 analogues • Sitagliptin • Vildagliptin • Saxagliptin • Alogliptin coming soon • Exenatide • Liraglutide

17. Indications: Sitagliptin • Monotherapy if Metformin is not tolerated and SU unsuitable • Part of dual therapy with SU or Metformin or TZD • Part of triple therapy with combination of Metformin + SU or Metformin + TZD • Dose 100mg OD • Avoid if eGFR less than 50 mL/minute/1.73 m2

18. Vildagliptin • In combination with Metformin 50 mg BD • In combination with TZD 50 mg BD • In combination with SU 50 mg OD • Monitor LFT’s; avoid if eGFR less than 50 mL/minute/1.73 m2

19. DPP-4 inhibitors SE • Hypos are rare • Increased risk of nasopharyngitis • Increase the RR of UTI 1.5x • 50,000 UTIs on 1,000, 000 patients treated • Avoid in patients with recurrent UTI’s?

20. Exenatide • GLP-1 analogue • 5-10 ug BD • Injection • Licensed with SU/ Metformin or in combination • Induces ~2kg weight loss

21. Exenatide • HbA1c reduction ~ 1% • FPG reduction of 1.5 mmol/l • Reduction in postprandial hyperglycaemia • Rare hypos • Nausea and vomiting • ? pancreatitis

22. TZD’s (Glitazones)

23. Thiazolidinedions (Glitazones) • Reduce HbA1c by 1-2% • Peripheral vascular resistance : 4 mmHg in 24-h mean systolic and diastolic blood pressure • Lipids • - Convert small, dense LDL particles to large, buoyant LDL particles • - Increase plasma HDL cholesterol • - Decrease plasma triglycerides if they are elevated (>200 mg/dl)

24. TZD’s • Rosiglitazone: Nissen’s Meta-analysis • CVD: PERISCOPE, PRO-ACTIVE • LVF • ♯ predominantly♀ • Weight gain, oedema

25. NICE guidelines on 2nd & 3rd Line treatments

26. Sulphonylureas • Start low cost (not glibenclamide) when indicated • Educate about the risk of hypoglycaemia • PPGs

27. Drugs & Combinations • Exenatide • Pioglitazone ± Metformin • Rosigltazone + Metformin • Sitagliptin • Vildagliptin ± Metformin • Litaglutade is not covered by the guideline

28. TZD’s Cautions/ Precautions • Warn about significant oedema and tell the person what to do if it happens • Do not start if evidence of LVF or high risk of fracture • When selecting a glitazone take into account most up-to-date advice, safety and cost issues

29. TZD’s Cautions • Do not commence in a person who has a heart failure or history of heart failure • Do not commence in a person who is at a higher risk of fracture!!!

30. Exenatide • HbA1c> 7.5% • BMI (Caucasian)> 35 • Has specific psychological, biochemical or physical problems arising from high body weight • Would otherwise be starting TZD or insulin. • Continue if of 1% in A1c over 6 months and BW of 3% at 6 months

31. Acarbose • If unable to tolerate other medications

32. Biphasic Insulin • HbA1c > 9.0%. • Biphasic Analogues • Immediate injection before the meals is preferred • Problems with hypos • Postprandial hyperglycaemia is a problem

33. Developments that followed the guidelines

34. We will briefly mention... • Liraglutide • Saxagliptin • 4T Study

35. Guidance Summary • A1c 6.5% ( ? 7.5%) • BP 130/80mmHg (140/80) mmHg) • Cholesterol 4mmol/l • LDL 2mmol/l • Triglycerides 4.5mmol/l • Eyes, Kidneys, Nerves: Screen annually

36. www.EndoDiabetes.com