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GLP1 treatment options

GLP1 treatment options. May 2014. Incretin Effect. Incretin Hormones. Incretin hormones are produced by the gastrointestinal tract in response to nutrient entry and are necessary for the maintenance of glucose homeostasis. GLP 1 (glucagon like pepetide 1)

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GLP1 treatment options

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  1. GLP1 treatment options May 2014

  2. Incretin Effect

  3. Incretin Hormones Incretin hormones are produced by the gastrointestinal tract in response to nutrient entry and are necessary for the maintenance of glucose homeostasis. GLP 1 (glucagon like pepetide 1) GIP ( glucose dependent insulinotrophic polypeptide) Beyond Glycemic Control: The Effects of Incretin Hormones in Type 2 Diabetes -- Martin 34 (3): 66S -- The Diabetes Educator

  4. Therapeutic potential of GLP-1 and GIP The incretin effect is diminished in patients with type 2 diabetes1,2 GIP secretion is normal, but its action is diminished GLP-1 secretion is diminished, but its action is preserved 1Nauck MA, et al. J Clin Invest 1993;91:301–307; 2Nauck M, et al. Diabetologia 1986;29:46–52; 3Nauck MA, et al. Diabetologia 1993;36:741–744; 4Larsson H, et al. Acta Physiol Scand 1997;160:413–422; 5Drucker DJ. Diabetes Care 2003;26:2929–2940.

  5. GLP-1 Effects in Humans: Understanding the Glucoregulatory Role of Incretins GLP-1 secreted upon the ingestion of food Promotes satiety and reduces appetite a-cells: ↓ Postprandialglucagon secretion Liver: ↓ Glucagon reduces hepatic glucose output Other effects ? Skeletal muscle ? Adipose Tissue Cardiac Tissue Pulmonary b-cells:Enhances glucose-dependent insulin secretion Stomach: Helps regulate gastric emptying GLP-1: Glucagon-like peptide 1 Adapted from Flint A, et al. J Clin Invest. 1998;101:515-520; Adapted from Larsson H, et al. Acta Physiol Scand. 1997;160:413-422; Adapted from Nauck MA, et al. Diabetologia. 1996;39:1546-1553; Adapted from Drucker DJ. Diabetes.1998;47:159-169.

  6. Combinations options

  7. HbA1c ≥ 59mmol/mol HbA1c ≥ 59mmol/mol HbA1c ≥ 59mmol/mol Metformin + sulphonylurea HbA1c ≥ 59mmol/mol HbA1c ≥ 48mmol/mol Start insulin Sulphonylurea Sulphonylurea + DPP4 inhibitor or a TZD Blood-glucose lowering therapy – CG 87 algorithm – in entirety HbA1c < 6.5% Monitor for deterioration HbA1c ≥ 59mmol/mo HbA1c ≥ 6.5%1 after trial of lifestyle interventions HbA1c ≥ 48mmo/mol HbA1c ≥ 59mmol/m HbA1c < 7.5% Monitor for deterioration HbA1c < 7.5% Monitor for deterioration Metformin HbA1c < 7.5% Monitor for deterioration HbA1c < 7.5% Monitor for deterioration HbA1c < 7.5% Monitor for deterioration HbA1c < 7.5% Monitor for deterioration HbA1c < 6.5% Monitor for deterioration Consider adding a DPP4 inhibitor or a TZD if metformin is not tolerated or is contraindicated Metformin + DPP4 inhibitor or a TZD Add insulin - particularly if subject is markedly hyperglycaemic Insulin + metformin + sulphonylurea Metformin + SU + sitagliptin or Metformin + SU + TZD or Metformin + SU + exenatide Consider sulphonylurea 4 here if: • not overweight (tailor the assessment of body-weight-associated risk according to ethnic group 3), or • metformin is not tolerated or is contraindicated, or • a rapid therapeutic response is required because of hyperglycaemic symptoms Increase insulin dose and intensify regimen over time Consider pioglitazone with insulin if: • A TZD has previously had a marked glucose-lowering effect, or • Blood-glucose control is inadequate with high-dose insulin Consider a sulphonylurea for people with erratic lifestyles Consider substituting a DPP4 inhibitor or a TZD for an SU if there is significant risk of hypos or an SU is contraindicated or is not tolerated Consider adding DPP4 inhibitor or TZD if insulin is unacceptable (employment, social issues, obesity) Consider adding exenatide to metformin and SU if: • BMI ≥ 35 in patients of European descent, or • BMI < 35 and insulin unacceptable or weight-loss would benefit other co-morbidities SGLT2 NICE CG87

  8. Metformin SU DPP4 inhibitor TZD Blood-glucose lowering therapy – Therapeutic choices Insulin resistance Driver • Add to Met • Add to SU • Add to Met • Add to SU • Add to Met • Add to SU SU SGLT2 Consider First Consider Second Hypoglycaemia a concern Driver Elderly Consider eGFR Weight an issue eGFR>60 Under 75 No Thrush No UTI No Diuretics No postural hypotension

  9. SU Metformin DPP4 inhibitor TZD NPH Insulin Other Insulin TZD DPP-4 inhibitor Blood-glucose lowering therapy – Therapeutic choices • Add to Met • Add to SU ? • Add to Met • Add to SU • Add to Met • Add to SU SU As per CG66 • Added to Met + SU • Added to Met + SU if poor response to TZD or not tolerated. • Added to Met + SU • Added to Met + SU if poor response to DPP-4 inhib or not tolerated. • Long-acting analogue – as an alternative to starting NPH • Premix insulin as per CG66 • Added to Met + SU • Added to Met + Pio Currently not recommended Canagloflozin will be given Triple SGLT2 GLP 1 SGLT2 HbA1c ≤ 48mmol/mol Monitor for deterioration Did treatment added result in drop in HbA1c? Consider First Consider Second Consider Third

  10. SU Metformin DPP4 inhibitor TZD Other Insulin TZD Canagloflozin NPH Insulin NPH Insulin Other Insulin DPP-4 inhibitor Blood-glucose lowering therapy – Therapeutic choices • Add to Met • Add to SU • Add to Met • Add to SU • Add to Met • Add to SU SU • Long-acting analogue – as an alternative to starting NPH • Premix insulin • Added to Met + SU • Added to Met + Pio • Added to Met + SU • Added to Met + SU if poor response to DPP-4 inhib or not tolerated. • Added to Met + SU • Added to Met + Pio • Added to Met + SU • Added to Met + SU if poor response to TZD or not tolerated. • Long-acting analogue – as an alternative to starting NPH • Premix insulin • Added to Met + SU • Added to Met + Pio • Stop Gliptin/SGLT2 SGLT2 GLP 1 HbA1c ≤ 48mmol/mol Monitor for deterioration Did treatment added result in drop in HbA1c? Consider First Consider Second Consider Third • Added to Met + SU • Added to Met +SGLT2 Consider Fourth GLP 1 • Added to Met + SU • Added to Met + pio • Added to Met +GLP1 Stop Gliptin /SGLT2/ PIO

  11. Group work

  12. Case study - 1 Mr S • Type 2 for 8yrs • Last 3 HbA1c’s 60 mmol/mol, 66 and 73 mmol/mol • Metformin MR 1500mg, Pioglitazone 15mg, Glimepiride 4mg • BMI 35 • Factory manager – works shifts

  13. Case study - 1 Mr S • Type 2 for 8yrs • Last 3 HbA1c’s 60 mmol/mol, 66 and 73 mmol/mol • Metformin MR 1500mg, Pioglitazone 15mg, Glimepiride 4mg • BMI 35 • Factory manager – works shifts GLP1 –an option BMI >35 HbA1c <75mmol/mol

  14. Case Study - 2 Mr M • Devout Moslem – prays 5x/day and fasts for Ramadan • Eats 9am, 12md, 4pm and 9pm • Metformin 850mg BD , Pioglitazone 30mg and Glimepiride 4mg OD • Last 3 HbA1c’s 63, 69,74 mmol/mol • BMI 30 • Speaks some English

  15. Case Study - 2 Mr M • Devout Moslem – prays 5x/day and fasts for Ramadan • Eats 9am, 12md, 4pm and 9pm • Metformin 850mg BD , Pioglitazone 30mg and Glimepiride 4mg OD • Last 3 HbA1c’s 63, 69,74 mmol/mol • BMI 30 • Speaks some English GLP 1 an option BMI 30 – meets NICE- ethnicity adjusted HbA1c <75mmol/mol

  16. Case Study - 3 Mrs B • Last 3 HbA1c’s 56, 65 and 77mmol/mol • BMI 25 • Glimepiride 4mg OD, Metformin 500mg TDS, Pioglitazone 30mg OD • Not happy about HBGM

  17. Case Study - 3 Mrs B • Last 3 HbA1c’s 56, 65 and 77mmol/mol • BMI 25 • Glimepiride 4mg OD, Metformin 500mg TDS, Pioglitazone 30mg OD • Not happy about HBGM GLP1 not an option BMI 25 HbA1c rising rapidly needs insulin

  18. Case study 4 • Mr D • 42 year old sales rep • Type 2 diabetes for 6 years • Has managed to lose 3 stone in weight since diagnosis. • BMI 27 • Last 3 HbA1c’s 50, 75, and 90 mmol/mol • Metformin MR 1500mg OD, Glimepiride 4mg OD,

  19. Case study 4 • Mr D • 42 year old sales rep • Type 2 diabetes for 6 years • BMI 35 • Last 3 HbA1c’s 50, 75, and 90 mmol/mol • Metformin MR 1500mg OD, Glimepiride 4mg OD, GLP 1 not an option HbA1c rising rapidly needs insulin

  20. Injection Technique On the diagrams provided draw anatomically correct possible injection sites

  21. Anatomy of the Skin 23

  22. Ideal Distribution of Insulin

  23. Injection Sites

  24. Lifting a Skin Fold

  25. Options for injection rotation

  26. Hypoglycaemia 4 is the floor

  27. Mild Hypoglycaemia • Tingling hands,feet,lips or tongue • Sweating • Dizziness • Trembling Hunger • Blurred vision • Difficulty in concentration • Palpitations • Occasional headaches

  28. 4-6 Dextrose tablets Glucochek 1-2 100mls lucozade 4-5 jelly babies Eat next meal if due OR Have a snack, e.g. banana/bread /biscuits etc Mild “hypo” – treatment15-20g CHO

  29. DVLA to be informed • Insulin treated • Class 2 on any oral medication or injectable

  30. Car Driver At risk of Hypoglycaemia Insulin –Treated • Within 2 hours of commencing driving and every 2 hours whilst driving • Do not drive if BGL less than 4mmols • If BGL less than 5mmols treat with snack • If hypoglycaemia develops while driving ,stop ,switch off engine, remove keys from ignition & move from driver’s seat. • Treat hypoglycaemia with glucose tablets/carbohydrate. Do not resume driving for 45 mins after blood glucose back to normal. Sulphonylureas and Glindes • It may be appropriate to test regularly at times relevant to driving

  31. Questions

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