Insulin 301 abbotsford

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  • This slide must be visually presented to the audience AND verbalized by the speaker.
  • This slide must be visually presented to the audience AND verbalized by the speaker.
  • May start Metformin at the time of diagnosisChange to 8.5% as threshold Start metformin immediately as an optionConcept of individualizing therapy based on patient and agent characteristicsWith that in mind, the next figure shows the characteristics of the agents ….
  • Concept of RELATIVE A1c lowering – not absoluteConcept of RELATIVE cost considerationsChange to achieve target within 3-6 months.
  • Although there may be a number of different insulins to try to remember, it is much simpler to remember that there really are only 3 types of insulin: Basal, Bolus, Premixed.
  • Starting with the bolus insulins … the traditional insulin is shows as Human Regular. It was good for its time but to make a better time-action profile that would match the “boluses” of food better, the profile was made to have faster onset, faster peak and faster disappearance.On the basal side, the traditional insulin is NPH which is a cloudy insulin requiring resuspension. To make a better basal, the profile was flattened and lengthened as with the 2 basal analogues. The premixed insulins are mixtures of basal and bolus in a predetermined ratio.
  • In keeping with the Rules of 3s, there are 3 basic regimens
  • SELECT WHAT YOU THINK IS CORRECT
  • SELECT WHAT YOU THINK IS CORRECT
  • If there is insulin resistance, the increments by which one increases both SC or IV insulin would be significantly greater
  • CLICK ON ACTIVE HYPERLINK TO CONNECT TO THE CDA CPG TOOL TO DEMONSTRATE THE INDIVIDUALIZATION OF PHARMA THERAPY IN T2DM
  • Insulin 301 abbotsford

    1. 1. Insulin 301: Cases! Dr. Sara Stafford Fraser Health Division of Endocrinology 13 January 2014
    2. 2. Conflict Disclosure Information Speaker: Dr. Sara Stafford Title of Talk: Insulin 301 FINANCIAL DISCLOSURE Grants/Research Support: None Speakers Bureau/Honoraria: Consulting Fees: Eli Lilly, Boehringer Ingelheim, Novo Nordisk, Sanofi Aventis, Merck None Research Funding: None Other: None
    3. 3. CFPC CoI Templates: Slide 2 Disclosure of Commercial Support • This program has received financial support from Sanofi Canada Inc. in the form of an educational grant. • This program has received in-kind support from Sanofi Canada Inc. in the form of logistical support for the meeting. • Potential for conflict(s) of interest: – Dr. Stafford has received an honorarium from Sanofi Canada Inc. whose product(s) are being discussed in this program. – Sanofi Canada Inc. benefits from the sale of a product that will be discussed in this program: Glulisine (Apidra), Glargine (Lantus)
    4. 4. CFPC CoI Templates: Slide 3 Mitigating Potential Bias • Only published data will be presented in this program and recommendations will be based on the CDA Clinical Guidelines and evidence via published clinical trials.
    5. 5. Learning objectives By the end of this session, you will be able to : 1. Name the 3 types of insulin, 3 insulin regimens and pros/cons of each 2. Select the regimen best suited for a particular patient with dosing and titration 3. Address issues in patients on glucocorticoids, dialysis, acute infection, parenteral feeds
    6. 6. guidelines.diabetes.ca guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association
    7. 7. Individualizing A1C Targets 2013 Consider 7.1-8.5% if: which must be balanced against the risk of hypoglycemia guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca guidelines.diabetes.ca | Diabetes Association Copyright © 2013 Canadian1-800-BANTING (226-8464) | diabetes.ca
    8. 8. AT DIAGNOSIS OF TYPE 2 DIABETES Start lifestyle intervention (nutrition therapy and physical activity) +/- Metformin L I F E S T Y L E A1C < 8.5% If not at glycemic target (2-3 mos) Start / Increase metformin A1C 8.5% Symptomatic hyperglycemia with metabolic decompensation Start metformin immediately Consider initial combination with another antihyperglycemic agent Initiate insulin +/metformin If not at glycemic targets Add an agent best suited to the individual: Patient Characteristics Degree of hyperglycemia Risk of hypoglycemia Overweight or obesity Comorbidities (renal, cardiac, hepatic) Preferences & access to treatment Other Agent Characteristics BG lowering efficacy and durability Risk of inducing hypoglycemia Effect on weight Contraindications & side-effects Cost and coverage Other 2013 See next page…
    9. 9. From prior page… L I F E S T Y L E If not at glycemic target • Add another agent from a different class • Add/Intensify insulin regimen 2013 Make timely adjustments to attain target A1C within 3 to 6 months
    10. 10. 3 Types of insulins BOLUS • Regular or Toronto • Apidra (glulisine) • Humalog (lispro) • Novorapid (aspart) BASAL • NPH • Lantus (glargine) • Levemir (detemir) PRE-MIXED • 30/70 • Humalog Mix25, Mix50 (insulin lispro/lispro protamine) • Novomix 30 (biphasic insulin aspart) Canadian Diabetes Association Clinical Practice Guidelines. Can J Diabetes 2013; in press
    11. 11. Relative Glycemic Effect Lispro Aspart glulisine Human Regular NPH Detemir Glargine 0 12 24 Duration in Hours PRE-MIXED: 30/70, Humalog Mix25, Mix50, Novomix 30 McMahon GT, Dluhy RG. NEJM 2007;357:1759.
    12. 12. CDA 2013 Clinical Practice Guidelines: Pharmacologic therapy in type 2 diabetes Recommendation #5: When basal insulin is added to antihyperglycemic agents, long-acting analogues (detemir or glargine) may be used instead of intermediate-acting NPH to reduce the risk of nocturnal and symptomatic hypoglycemia [Grade A, Level 1A] guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca
    13. 13. CDA 2013 Clinical Practice Guidelines: Pharmacologic therapy in type 2 diabetes Recommendation #6: When bolus insulin is added to antihyperglycemic agents, rapid-acting analogues (insulin aspart, glulisine, or lispro) may be used instead of regular insulin to reduce the risk of hypoglycemia [Grade A, Level 1A] guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca
    14. 14. Normal Insulin Secretion: The Basal-Bolus Insulin Concept Endogenous Insulin Insulin effect Bolus Insulin Basal Insulin B L D HS Time of administration B = breakfast; L = lunch; D = dinner; HS = bedtime. 1. Leahy JL. In: Leahy JL, Cefalu WT (eds). Insulin Therapy. Marcel Dekker Inc., New York, 2002. 2. Bolli GB, et al. Diabetologia 1999; 42:1151-67.
    15. 15. 3 Insulin Regimens
    16. 16. Basal alone Endogenous Insulin Insulin effect Bolus Insulin Basal Insulin B L D Time of administration B = breakfast; L = lunch; D = dinner; HS = bedtime. HS
    17. 17. Basal-Bolus Endogenous Insulin Insulin effect Bolus Insulin Basal Insulin B L D HS Time of administration B = breakfast; L = lunch; D = dinner; HS = bedtime. 1. Leahy JL. In: Leahy JL, Cefalu WT (eds). Insulin Therapy. Marcel Dekker Inc., New York, 2002.
    18. 18. Basal Plus Bolus Endogenous Insulin Insulin effect Bolus Insulin Basal Insulin B L D Time of administration HS
    19. 19. BID Premixed Insulin effect Endogenous Insulin B L D Time of administration HS
    20. 20. Intensification of Therapy in T2DM FBG at target A1C above target Basal bolus Additional prandial doses as needed FBG above target A1C above target Basal Plus A1C above target Add prandial insulin at main meal Basal Add basal insulin and titrate OHA monotherapy and combinations Lifestyle changes Progressive deterioration of -cell function OHA=oral hypoglycaemic agent Adapted from Raccah D. et al. Diabetes/Met Res & Rev 2007;23:257-64.
    21. 21. Intensification of Therapy in T2DM FBG at target A1C above target Basal bolus Additional bolus doses as needed FBG above target A1C above target Basal Plus Add bolus insulin at main meal A1C above target Basal Add basal insulin and titrate OHA monotherapy and combinations Lifestyle changes Progressive deterioration of -cell function OHA=oral hypoglycaemic agent Adapted from Raccah D. et al. Diabetes/Met Res & Rev 2007;23:257-64.
    22. 22. What about the orals? • METFORMIN • METFORMIN • METFORMIN • • • • Secretagogues if basal alone TZD – stop DPP-4 – benefit but cost GLP-1 receptor agonist – benefit (dose & weight) but cost
    23. 23. Cases
    24. 24. Patrick 54yo man with DM2 X 5 years DEC 6m ago, trying to manage his lifestyle, but he is on the road with his sales job.
    25. 25. • PMH: Hypertension, dyslipidemia, appendectomy, exsmoker (quit 5 years ago) • Meds: Metformin 1g BID, gliclazide MR 120 mg OD, sitagliptin 100 mg OD, acarbose 50 mg TID, simvastatin 40 mg qhs, perindopril 8 mg OD, amlodipine 5 mg OD • On exam: Obese (wt 100kg, ht 175 cm, WC 104 cm), BP 130/80 mmHg, HR 72 regular. Acanthosis nigricans. Monofilament normal. • Labs: A1c 8.2%; TC 4.23, TG 1.99, HDL 1.00, LDL 1.9 mmol/L; Cr 125 umol/L; ACR 2.3
    26. 26. Log Book Breakfast Before Monday 10.2 Tuesday After Lunch Before 9.8 Wednesday 8.7 9.7 After Dinner Before 11.5 Bedtime After 12.2 10.1 12.5 8.4 Thursday 10.4 7.6 Friday 10.1 8.7 Saturday 9.9 9.4 9.2 9.9 Sunday 8.7 10.2 11.8 13.8 13.1 Where are the lows and highs? Why are there lows and highs? Adjust / switch / add? – first fix lows, then highs Insulin Dose
    27. 27. What is your next step? 1. 2. 3. 4. 5. Add basal insulin and keep the SU Add basal insulin and stop the SU Add premixed BID and stop the SU Add Basal Bolus and stop the SU Add Basal and one Bolus
    28. 28. What about the other orals? Metformin 1g BID Gliclazide MR 120 mg OD Sitagliptin 100 mg OD Acarbose 50 mg TID
    29. 29. Insulin Dosage Instructions (Example) 4-7 • Your target fasting blood sugar level is _______ mmol/L 10 • You will inject ______ units of insulin each day • You will continue to increase by 1 unit every day until 4-7 your blood sugar level is _______ mmol/L before breakfast • Do not increase your insulin when your fasting blood 4-7 sugar is _______ mmol/L
    30. 30. Breakfast Before After Lunch Before After Supper Before After Bedtime Dose Sunday 9.7 7.8 7.5 22 Monday 9.4 7.6 6.9 23 Tuesday 9.0 8.9 6.5 7.8 24 Wednesday 9.1 8.5 7.5 25 Thursday 8.8 Metformin 1000 mg p.o. b.i.d. Gliclazide MR 120 mg p.o. o.d. Acarbose and Sitagliptin were d/c’d to convince him to go on insulin
    31. 31. What is your next step? 1. 2. 3. 4. 5. Keep titrating the basal Add bolus insulin Change to premixed BID Add basal in the AM Add GLP-1 analogue
    32. 32. • Patrick has been titrating up his long-acting basal insulin at bedtime as instructed and has achieved the target fasting blood glucose levels of 4-7 mmol/L. He remains on metformin 1g BID and gliclazide MR 120 mg od. He has no symptoms of hypoglycemia. Here is his logbook. What should be done now?
    33. 33. Breakfast Lunch Before After Before Monday 7.7 7.1 Tuesday 8.3 Wednesday 7.1 Thursday 6.9 Friday 9.0 Saturday 8.1 Sunday 8.2 After Dinner Bedtime Insulin Dose Before After 6.2 4.9 6.3 46 7.3 4.4 5.9 4.1 4.0 47 47 5.9 4.0 8.9 45 48 49 6.1 Where are the lows and highs? Why are there lows and highs? Adjust / switch / add? 50
    34. 34. What would you do now? 1. 2. 3. 4. 5. Add basal in the morning Increase the basal at bedtime Reduce/stop the gliclazide MR Change to premixed BID 2+3
    35. 35. Breakfast Lunch Before After Before Monday 7.7 7.1 Tuesday 8.3 After Dinner Bedtime Insulin Dose Before After 6.2 4.9 Continue increasing bedtime 7.1 6.3 7.3 Thursday 6.9 4.4 basal insulin Wednesday Friday 9.0 5.9 4.1 5.9 Decrease gliclazide MR dose 8.1 4.0 Saturday Sunday 8.2 8.9 4.0 6.1 Where are the lows and highs? Why are there lows and highs? Adjust / switch / add? 45 46 47 47 48 49 50
    36. 36. Breakfast Before After Lunch Before After Supper Before After Bedtime Dose Sunday 6.5 6.2 5.0 7.2 55 Monday 5.9 5.9 5.7 6.9 55 Tuesday 5.7 5.5 6.0 6.7 55 Wednesday 5.8 5.8 6.2 6.5 55 Thursday 5.5 5.1 Metformin 1000 mg p.o. b.i.d. Gliclazide MR 90 mg p.o. o.d.
    37. 37. Patrick (3 years later) • Meds: Metformin 1g BID, gliclazide MR 120 mg OD, glargine 55 units qhs, simvastatin 40 mg qhs, perindopril 8 mg od, amlodipine 10 mg od • On exam: Obese (wt 104kg, ht 175 cm, WC 108 cm), BP 120/80 mmHg, HR 72 regular. Acanthosis nigricans noted. Eyes – no abnormality. Rest normal. • Labs: A1c 8.1%; Cr 130 umol/L Why did Patrick need for his gliclazide MR to be increased back to 120 mg over time?
    38. 38. Breakfast Before Monday 6.1 Wednesday 5.5 Thursday 5.8 Friday 5.2 Saturday 6.4 Sunday 7.1 After 5.9 Tuesday Lunch Before 10.0 12.3 After Dinner Before Bedtime After 7.5 7.1 55 7.8 8.7 10.1 6.1 55 6.4 8.1 55 6.9 9.1 55 55 7.6 11.5 Insulin Dose 6.4 Where are the lows and highs? Why are there lows and highs? Adjust / switch / add? 55 5.9 55
    39. 39. What would you do next? 1. 2. 3. 4. 5. Add basal in the morning Increase the basal at bedtime Change to premixed BID Add bolus insulin at all meals Add bolus insulin at breakfast
    40. 40. Breakfast Before Monday 6.1 After 5.9 Tuesday Lunch Before 10.0 12.3 After Dinner Before Bedtime After 7.5 7.1 55 7.8 Add bolus insulin at breakfast 5.5 8.7 Wednesday Thursday 5.8 Friday 5.2 Saturday 6.4 Sunday 7.1 10.1 7.6 55 6.1 55 55 6.9 9.1 55 6.4 8.1 11.5 Insulin Dose 6.4 Where are the lows and highs? Why are there lows and highs? Adjust / switch / add? 55 5.9 55
    41. 41. If you were to add bolus at breakfast, how much? 1. 2. 3. 4. 2 units 4 units 8 units 20 units
    42. 42. James • • • • • • 66 year old man, 96 kg T2DM x 5 years on metformin/ glyburide Admitted for urosepsis A1c 8.0% Not eating and drinking well Creatinine 245 umol/L, eGFR 27 mL/min
    43. 43. What would you do now? 1. Sliding scale bolus insulin QID 2. Start IV insulin 3. Resume oral agents 4. Basal + bolus therapy 5. Basal insulin SC OD
    44. 44. What are the issues in a patient with renal failure?
    45. 45. Considerations in renal failure • • • • Limitations of therapies Reduced clearance of insulin Reduced renal gluconeogenesis Altered eating habits Park J et al. Curr Diab Rep 2012;12:432-39.
    46. 46. Antihyperglycemic agents and Renal Function CKD Stage: GFR (mL/min): 5 < 15 4 15-29 3 30-59 2 60-89 1 ≥ 90 25 Acarbose 30 Metformin Linagliptin 15 Saxagliptin 15 Sitagliptin 25 mg 60 2.5 mg 30 50 mg 50 30 Exenatide 50 50 Liraglutide Gliclazide/Glimepiride Glyburide 50 15 30 30 50 Repaglinide Thiazolidinediones 30 Not recommended / contraindicated Caution and/or dose reduction Safe Adapted from: Product Monographs as of March 1, 2013; CDA Guidelines 2008; and Yale JF. J Am Soc Nephrol 2005; 16:S7-S10.
    47. 47. 1. Sliding scale bolus insulin QID 2. Start IV insulin 3. Resume oral agents 4. Basal + bolus therapy 5. Basal insulin SC OD ?
    48. 48. • Humulin R or Novolin Toronto SC QID BS <8 8.1-12 12.1-16 16.1-20 >20 Insulin 0 2 units 4 units 6 units 10 units
    49. 49. Sliding scale insulin - evil • Sliding scale insulin without a basal insulin is purely REACTIVE and allows for hyperglycemia (Queale WS. et al. Arch Int Med 1997;157) (AACE/ADA Consensus Statement 2009)
    50. 50. Sliding scale insulin alone results in variable glucose control 16.5 BG (mmol/L) +6 U 14.0 +4 U Sliding Scale alone BG (mmol/L) <4 0U Breakfast Lunch Dinner 3.0 Bedtime Bolus insulin QID QID: four times daily; SSI: sliding-scale insulin; BG: blood glucose 6 > 19.0 0U 4 16.1 – 19.0 4.0 2 13.1 – 16.0 6.0 0 10.1 – 13.0 6.0 Call MD 4.1 – 10.0 10.0 Bolus insulin (U) Call MD
    51. 51. NPO • IV insulin – For 96 kg = TDI (SC) = 0.5u/kg = 48 units/d – IV TDI ≈ ½ SC TDI – 1.0 units / hr IV insulin at optimal glucose – If on home insulin, TDI = total of home dose • SC long-acting basal analogue OD – TDI x 50% = 24 units SC once daily • SC NPH q12h – 12 units SC q12h – Or can use the TDI dose given the potential insulin resistance Wesorick D, et al. J Hosp Med 2008;3(5 Suppl):17-28.
    52. 52. Basal insulin Endogenous Insulin Insulin effect Bolus Insulin Basal Insulin B L D HS Time of administration B = breakfast; L = lunch; D = dinner; HS = bedtime. 1. Leahy JL. In: Leahy JL, Cefalu WT (eds). Insulin Therapy. Marcel Dekker Inc., New York, 2002. 2. Bolli GB, et al. Diabetologia 1999; 42:1151-67.
    53. 53. Caveats • Insulin resistance – Greater rate of increase in insulin doses for both SC or IV • Acute infection – ++ insulin resistant state – Requirements may double – Increase requirements by 30%
    54. 54. James (cont’d) • Basal insulin SC continued • 2 days post-admission, starting to eat and drink • Cr 195 umol/L • DM management now?
    55. 55. 1. Continue SC basal insulin with no changes 2. Add bolus insulin with each meal + continue basal SC dose + supplemental bolus insulin 3. D/C basal SC insulin - resume oral agents 4. D/C basal SC insulin – begin sliding scale bolus insulin QID
    56. 56. Basal-Bolus Endogenous Insulin Insulin effect Bolus Insulin Basal Insulin B L D HS Time of administration B = breakfast; L = lunch; D = dinner; HS = bedtime. 1. Leahy JL. In: Leahy JL, Cefalu WT (eds). Insulin Therapy. Marcel Dekker Inc., New York, 2002.
    57. 57. Preferred inpatient insulin administration Routine / scheduled insulin Basal Bolus (prandial) Total daily insulin
    58. 58. Supplemental scale – good! • Supplements ROUTINE insulin • EXTRA bolus insulin ac meals ONLY • CORRECTS hyperglycemia • Can use supplemental needs to reassess standing doses
    59. 59. Preferred inpatient insulin administration Routine / scheduled insulin Basal Bolus (prandial) Correction / Supplemental Total bolus insulin given at mealtime Total daily insulin
    60. 60. You choose to start basal-bolus regimen with bolus supplemental scale at meals. What doses will you order?
    61. 61. Total daily insulin = 0.5 units / kg 50% 50% Bolus for the day 1/3 Bolus Breakfast 1/3 Bolus Lunch Basal dose 1/3 Bolus Dinner
    62. 62. • Basal 24 units SC qhs • Bolus 8 units SC ac meals • Bolus SC supplemental scale ac meals BS Insulin <4 call MD 4.1-10 0 units 10.1-13 2 units 13.1-16 4 units 16.1-19 6 units >19 10 units
    63. 63. His eating is actually quite variable. How would you modify his insulin regimen to accommodate this? 1. Routine basal + sliding scale bolus 2. Routine basal + routine bolus (pc meals if pt eats > 50% of tray) 3. Supplemental scale bolus only 4. Routine basal only
    64. 64. Variable Eating • Need BASAL insulin (NPH bid or detemir / glargine OD) • Can give the BOLUS insulin immediately pc meals *** if using rapid insulin analogues
    65. 65. He is having difficulties swallowing and is assessed by speech-language pathology and deemed to be inappropriate for oral intake. He is now on continuous enteral feeds. 1. 2. 3. 4. Routine basal only Routine basal + routine bolus Routine basal + supplemental scale Routine bolus only
    66. 66. Enteral / Parenteral Feeds • Continuous feeds – Glargine or Detemir OD – NPH q 12 h (not BID!!) (TDI split into 2) • Bolus feeds – Time the insulin dosing to match the feed times – Regular insulin can be helpful here – Still need basal insulin
    67. 67. James (cont’d) • Over time, his ability to swallow improves and he is able to tolerate a full oral diet • He is then stabilized on: – Basal insulin 25 units qhs – Bolus insulin 10 units ac meals – Supplement bolus insulin as needed
    68. 68. James (cont’d) • Just 2 days before planned discharge, he develops acute right knee pain and left great toe pain • He is diagnosed with gout and is placed on PREDNISONE 40 mg OD x 5 days
    69. 69. What would you do with his insulin regimen? 1. Change nothing – it is only 5 days 2. Wait 2 days to see the pattern, then adjust his insulin 3. Increase the breakfast and lunch bolus doses and continue the dinner bolus and basal doses 4. Increase all the insulin doses
    70. 70. Glucocorticoids • Prednisone in AM = high glucose at lunch and supper but normal fasting • Increase existing doses at breakfast and lunch … may need to increase dinner too
    71. 71. Glucocorticoids • If naïve to insulin … – NPH in AM +/- Bolus insulin acB and acL (eg. 10 u NPH qAM, 5 NR acB, 8 NR acL) – Metformin 1g BID, repaglinide acB and acS (dose acL >> acB)
    72. 72. James (cont’d) Unfortunately, his renal function fails to improve and he ends up requiring chronic dialysis treatment … How will affect his insulin requirements and glycemic control?
    73. 73. Considerations in renal failure • • • • Limitations of therapies Reduced clearance of insulin Reduced renal gluconeogenesis Altered eating habits Park J et al. Curr Diab Rep 2012;12:432-39.
    74. 74. Don’t forget other meds to hold/stop when dehydrated
    75. 75. Counsel all Patients About Sick Day Medication List 2013
    76. 76. How can I remember the med choices in renal failure or other comorbidities?
    77. 77. guidelines.diabetes.ca guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association
    78. 78. http://guidelines.diabetes.ca/BloodGlucos eLowering/PharmacologyT2 guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association
    79. 79. Summary • Diabetes is PROGRESSIVE • Regimens need to CHANGE over time • Understand the time-action profiles to tailor the regimen and dosage to the patient’s needs
    80. 80. Summary • Renal dysfunction – Limitations with non-insulin antihyperglycemic agents – Need to modify as per dialysis schedule – May need lower doses of insulin until dialysis
    81. 81. Summary • Acutely ill patient – DO NOT use sliding scale only – Think Basal + Bolus + Correction regimen – Think increase usual dose + Correction • NPO patient: Basal only (SC or IV) • Enteral feeds: Basal only (if continuous) • Glucocorticoids: Remember steroid pattern
    82. 82. References 1. 2013 Canadian Diabetes Association clinical practice guidelines. Can J Diab 2013; in press 2. McMahon GT, Dluhy RG. Intention to treat – initiating insulin and the 4T study. N Engl J Med 2007;357:1759. 3. Leahy JL. In: Leahy JL, Cefalu WT (eds). Insulin Therapy. Marcel Dekker Inc., New York, 2002. 4. Bolli GB, Di Marchi RD, Park GD, et al. Insulin analogues and their potential in the management of diabetes mellitus. Diabetologia 1999; 42:1151-67. 5. Raccah D, Bretzel RG, Owens D, Riddle M. When basal insulin therapy in type 2 diabetes mellitus is not enough – what next? Diabetes Metab Res Rev 2007;23:257-64. 6. Harris SB, et al. START protocol. As presented at CDA/CSEM conference in Vancouver, BC, October 2012
    83. 83. References 7. Meneghini L, Mersebach H, Kumar S, et al. Comparison of 2 intensification regimens with rapid-acting insulin aspart in type 2 diabetes mellitus inadequately controlled by once-daily insulin detemir and oral antidiabetes drugs: The Step-Wise randomized study. Endocr Pract 2011;17:727-36. 7. Park J, Lertdumrongluk P, Molnar MZ, et al. Glycemic control in diabetic dialysis patients and the burnt-out diabetes phenomenon. Curr Diab Rep 2012;12:432-9. 8. Ontario College of Family Physicians Insulin Prescription Tool available at www.ocfp.on.ca

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