Initiation and Adjustment of Insulin Regimens for Type 2 Diabetes

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Types of Insulin Rapid-acting insulin: lispro (Humalog), aspart (NovoRapid), glulisine (Apidra) Regular short-acting insulin: Humulin R, Novolin ge Toronto, Hypurin Regular Basal insulin: NPH (Humulin N, Novolin ge NPH, Hypurin NPH), glargine (Lantus, Basaglar, Toujeo), detemir (Levemir) Premixed insulin: Rapid acting: NovoLog Mix 30, Humalog Mix 25 and 50 Short-acting: Humulin 30/70, Novolin ge 30/70, 40/60, and 50/50 This Clinical Resource gives subscribers additional insight related to the Recommendations published in PHARMACIST S LETTER / PRESCRIBER S LETTER March 2017 ~ Resource #330335 Initiation and Adjustment of Insulin Regimens for Type 2 Diabetes For guidance when to start insulin, please see our algorithm, Management of New-Onset Type 2 Diabetes. Initiate initial insulin regimen. B Adjust dose to meet goals. C Add mealtime insulin to largest meal. A,D,1 Adjust dose to meet goals. 1,E A. Typically, stop sulfonylureas, DPP-4 inhibitors, and GLP-1 agonists when starting mealtime insulin. 1 B. Example initial dose: basal insulin (e.g., NPH, insulin glargine, etc) 10 units or 0.1 to 0.2 units/kg at bedtime. 1,2 C. Adjust basal insulin by 10% to 15% or 2 to 4 units once or twice weekly. 1 Alternatively, teach motivated patients to increase dose by 1 unit daily if fasting glucose remains elevated. 2 For hypoglycemia, consider decreasing dose by 4 units or 10% to 20%. 1 D. Options for adding mealtime insulin (if A1C <8%, consider reducing basal insulin by same amount): 2 to 4 units, 0.1 unit/kg, or 10% of basal dose. 1,2 E. Increase by 1 to 2 units or 10% to 15% once or twice weekly. For hypoglycemia, consider decreasing dose by 2 to 4 units or 10% to 20%. 1 Insulin naive Receiving sliding scale insulin (SSI) only Receiving basal insulin with sliding scale Convert to Basal Therapy: Give 50% of average daily SSI dose as basal insulin. 3 OR initiate initial insulin regimen. B Adjust dose to meet goals. C Goals not met with 0.5 units/kg/day basal insulin (e.g., NPH, insulin glargine, etc). 1 If goals not met, add mealtime insulin to additional meal(s) D (i.e., basal-bolus) or consider switch to premix twice daily. 1 Adjust dose to meet goals. 1,E Decision to initiate SCHEDULED insulin therapy. Add GLP-1 agonist. 1 If not tolerated or A1C goal not met, change to insulin-only regimen. 1 If goals not met, add lunchtime premix, or consider switch to basal plus mealtime insulin at largest meal. 1 Eliminate SSI Insulin (basal plus correction doses OK in hospital 1 ): Calculate total SSI daily dose and add 50% to current basal insulin. 3 Adjust dose to meet goals. C Switch to premix twice daily. Give same total daily dose as basal but give 2/3 in the morning and 1/3 with dinner, or give half with breakfast and half with dinner. 1,A Adjust dose to meet goals. 1,E (Relatively inexpensive option). If goals not met, consider switch to the other insulin regimen (i.e., from basalbolus to premix three times daily, or vice versa). 1 Copyright 2017 by Therapeutic Research Center PharmacistsLetter.com ~ PrescribersLetter.com ~ PharmacyTechniciansLetter.com

(Clinical Resource #330335: Page 2 of 2) Users of this resource are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and internet links in this article were current as of the date of publication. Project Leader in preparation of this clinical resource (330335): Melanie Cupp, Pharm.D., BCPS References 1. Standards of medical care in diabetes 2017. Diabetes Care 2017;40(Suppl 1):S1-135. 2. Canadian Diabetes Association. Appendix 3: examples of insulin initiation and titration regimens in people with type 2 diabetes. http://guidelines.diabetes.ca/browse/appendices/app endix3. (Accessed December 4, 2016). 3. Munshi MN, Florez H, Huang ES, et al. Management of diabetes in long-term care and skilled nursing facilities: a position statement of the American Diabetes Association. Diabetes Care 2016;39:308-18. Cite this document as follows: Clinical Resource, Initiation and Adjustment of Insulin Regimens for Type 2 Diabetes. Pharmacist s Letter/Prescriber s Letter. March 2017. Evidence and Recommendations You Can Trust 3120 West March Lane, Stockton, CA 95219 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249 Copyright 2017 by Therapeutic Research Center Subscribers to the Letter can get clinical resources, like this one, on any topic covered in any issue by going to PharmacistsLetter.com, PrescribersLetter.com, or PharmacyTechniciansLetter.com

PL Detail-Document #310839 This PL Detail-Document gives subscribers additional insight related to the Recommendations published in PHARMACIST S LETTER / PRESCRIBER S LETTER August 2015 How to Switch Insulin Products Switching insulins should always be done with prescriber approval and close monitoring. Advise patients to closely monitor blood glucose levels after switching insulins. If switching between human insulin brands (e.g., Humulin R to Novolin ge Toronto, Humulin N to Novolin ge NPH), keep the number of units each day the same. The chart below provides information to help guide common insulin switch scenarios. See our PL Chart, Comparison of Insulins and Injectable Diabetes Meds, for meal timing, onset, peak, duration of action, and other information. Also see our PL Algorithm, Initiation and Adjustment of Insulin Regimens for Type 2 Diabetes. Clinical Scenario Recommendation/Comments NPH to long-acting NPH to insulin detemir (Levemir) Convert unit-per-unit. 1 Some patients on basal-bolus insulin may require more insulin detemir than NPH. 1 Give insulin detemir once daily, or divided twice daily if necessary for control. 2 Do not mix insulin detemir with other insulins. 2 NPH to insulin glargine (Lantus, Toujeo) NPH once daily: convert unit-per-unit and give once daily. 3,14 Long-acting to NPH Insulin detemir (Levemir) to NPH NPH twice daily: reduce total daily dose by 20% and give once daily. 3,14 May take >5 days to see the max effect of the selected dose of Toujeo. 14 Do not mix insulin glargine with other insulins. 3,14 Give NPH twice daily (e.g., 50:50 or 2/3 in AM and 1/3 before dinner or at bedtime). 4,5 Insulin glargine (Lantus, Toujeo) to NPH Convert unit-per-unit from Lantus. 4 No specific information to guide Toujeo to NPH switch. Consider 20% dose reduction to be conservative. Give NPH twice daily (e.g., 50:50 or 2/3 in AM and 1/3 before dinner or at bedtime). 4,5 Long-acting to long-acting Insulin detemir (Levemir) to insulin glargine (Lantus) Convert unit-per-unit. 6 Give once daily, or divided twice daily if necessary for control. 7 A lower daily dose may be needed. 8 Do not mix insulin glargine with other insulins. 3 Copyright 2015 by Therapeutic Research Center www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com

(PL Detail-Document #310839: Page 2 of 4) Clinical Scenario Long-acting to long-acting, continued Insulin detemir (Levemir) to insulin glargine (Toujeo) Insulin glargine (Lantus) to insulin glargine (Toujeo) Insulin glargine (Lantus) to insulin detemir (Levemir) Insulin glargine (Toujeo) to insulin glargine (Lantus) or insulin detemir (Levemir) Regular to rapid-acting Regular human insulin (Humulin R, Novolin ge Toronto) to rapid-acting insulin analog (insulin aspart [NovoRapid], insulin glulisine [Apidra], insulin lispro [Humalog]) Recommendation/Comments Levemir once daily: convert unit-per-unit and give once daily. 14 Levemir twice daily: reduce total daily dose by 20% and give once daily. 14 May take >5 days to see the max effect of the selected dose of Toujeo. 14 Do not mix insulin glargine with other insulins. 14 Convert unit-per-unit and give once daily. 14 For patients controlled on Lantus, expect that a higher daily dose (about 10% to 18%) of Toujeo will be needed to maintain control. 12,14 May take >5 days to see the max effect of the selected dose of Toujeo. 14 Do not mix insulin glargine with other insulins. 14 Convert unit-per-unit. 1,6 Give once daily, or divided twice daily if necessary for control. 2 If divided twice daily, a higher daily dose may be needed. 8 Do not mix insulin detemir with other insulins. 2 Reduce dose by about 20% when converting to Lantus to reduce hypoglycemia risk. 12 No info specific to Levemir; consider 20% dose reduction to be conservative.,9-11 Rapid-acting insulin analogs have a faster onset of action and a shorter duration of action than human regular insulin. See Comparison of Insulins and Injectable Diabetes Meds for specifics of meal timing. 15 Rapid-acting to regular Insulin aspart (NovoRapid), insulin glulisine (Apidra), or insulin lispro (Humalog) to regular human insulin (Humulin R, Novolin ge Toronto) Rapid-acting to rapid-acting Insulin aspart (NovoRapid), insulin glulisine (Apidra), or insulin lispro (Humalog) to insulin aspart (NovoRapid), insulin glulisine (Apidra), or insulin lispro (Humalog),9-11 Rapid-acting analogs have a faster onset and a shorter duration of action than human regular insulin. See Comparison of Insulins and Injectable Diabetes Meds for specifics of meal timing. 15,9-11 See Comparison of Insulins and Injectable Diabetes Meds for specifics of meal timing. Copyright 2015 by Therapeutic Research Center www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com

(PL Detail-Document #310839: Page 3 of 4) Clinical Scenario Premixed to premixed Premixed NPH/regular insulin (Humulin 30/70, Novolin ge 30/70) to premixed protamine/rapidacting analog (insulin lispro protamine/insulin lispro [Humalog Mix 25], insulin aspart protamine/insulin aspart [NovoMix 30]) Premixed protamine/rapid-acting analog (insulin lispro protamine/insulin lispro [Humalog Mix 25], insulin aspart protamine/insulin aspart [NovoMix 30]) to premixed NPH/regular insulin (Humulin 30/70, Novolin ge 30/70) Premixed NPH/regular insulin (Novolin ge 50/50) to premixed insulin lispro protamine/insulin lispro (Humalog Mix 50) Premixed insulin lispro protamine/insulin lispro (Humalog Mix 50) to premixed NPH/regular insulin (Novolin ge 50/50) Premixed insulin lispro protamine/insulin lispro (Humalog Mix 25) to Premixed insulin aspart protamine/insulin aspart (NovoMix 30) Premixed insulin aspart protamine/insulin aspart (NovoMix 30) to premixed insulin lispro protamine/insulin lispro (Humalog Mix 25) Recommendation/Comments,9,13 Premix analogs have a faster onset but similar duration compared to human premixes. See Comparison of Insulins and Injectable Diabetes Meds for specifics of meal timing. 15 Premix analogs have a faster onset but similar duration compared to human premixes. See Comparison of Insulins and Injectable Diabetes Meds for specifics of meal timing. 15,9 Premix analogs have a faster onset but similar duration compared to human premixed insulin. See Comparison of Insulins and Injectable Diabetes Meds for specifics of meal timing. 15 Premix analogs have a faster onset but similar duration compared to human premixed insulin. See Comparison of Insulins and Injectable Diabetes Meds for specifics of meal timing. 15 Users of this PL Detail-Document are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and internet links in this article were current as of the date of publication. Copyright 2015 by Therapeutic Research Center www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com

(PL Detail-Document #310839: Page 4 of 4) Project Leaders in preparation of this PL Detail- Document: Melissa M. Blair, BCPS, FCCP, FASHP (Original May 2014), Melanie Cupp, Pharm.D., BCPS (Update July 2015). References 1. Product information for Levemir. Novo Nordisk, Inc. Princeton, NJ 08540. February 2015. 2. Product monograph for Levemir. Novo Nordisk Canada Inc. Mississauga, ON L4W 5L6. December 2013. 3. Product monograph for Lantus. Sanofi-Aventis Canada Inc. Laval, QC H7V 0A3. July 2015. 4. U.S. Food and Drug Administration. Information regarding insulin storage and switching between products in an emergency. May 27, 2015. http://www.fda.gov/drugs/emergencypreparedness/u cm085213.htm. (Accessed July 16, 2015). 5. Kroon LA, Williams C. Diabetes mellitus. In: Alldredge BK, Corelli RL, Ernst ME, et al, editors. Koda-Kimble & Young s Applied Therapeutics: the Clinical Use of Drugs. 10 th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2013:1223-300. 6. King AB. Once-daily insulin detemir is comparable to once-daily insulin glargine in providing glycaemic control over 24 h in patients with type 2 diabetes: a double-blind, randomized, crossover study. Diabetes Obes Metab 2009;11:69-71. 7. DeVries JH, Nattrass M, Pieber TR. Refining basal insulin therapy: what have we learned in the age of analogues? Diabetes Metab Res Rev 2007;23:441-54. 8. Rosenstock J, Davies M, Home PD, et al. A randomized, 52-week, treat-to-target trial comparing insulin detemir with insulin glargine when administered as add-on to glucose-lowering drugs in insulin-naïve people with type 2 diabetes. Diabetologia 2008;51:408-16. 9. Product monograph for Humalog. Eli Lilly Canada Inc. Scarborough, ON M1N 2E8. April 2015. 10. Product monograph for Apidra. Sanofi-Aventis Canada. Laval, QC H7V 0A3. February 2014. 11. Product monograph for NovoRapid. Novo Nordisk Canada Inc. Mississauga, ON L4W 5L6. July 2014. 12. European Medicines Agency. CHMP postauthorization summary of positive opinion for Toujeo. February 26, 2015. http://www.ema.europa.eu/docs/en_gb/document_li brary/summary_of_opinion/human/000309/wc5001 83282.pdf. (Accessed July 16, 2015). 13. Product monograph for NovoMix 30. Novo Nordisk Canada Inc. Mississauga, ON L4W 5L6. August 2014. 14. Product monograph for Toujeo. Sanofi-Aventis Canada Inc. Laval, QC H7V 0A3. May 2015. 15. PL Detail-Document, Comparison of Insulins and Injectable Diabetes Meds. Pharmacist s Letter/Prescriber s Letter. August 2015. Cite this document as follows: PL Detail-Document, How to Switch Insulin Products. Pharmacist s Letter/Prescriber s Letter. August 2015. Evidence and Recommendations You Can Trust 3120 West March Lane, Stockton, CA 95219 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249 Copyright 2015 by Therapeutic Research Center Subscribers to the Letter can get PL Detail-Documents, like this one, on any topic covered in any issue by going to www.pharmacistsletter.com, www.prescribersletter.com, or www.pharmacytechniciansletter.com