Initiation and Adjustment of Insulin Regimens for Type 2 Diabetes

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1 PL Detail-Document # This Detail-Document accompanies the related article published in PHARMACIST S LETTER / PRESCRIBER S LETTER January 2014 Initiation and Adjustment of Insulin Regimens for Type 2 Diabetes For guidance when to start insulin, please see our PL Algorithm, Stepwise Treatment of Type 2 Diabetes. Note: Insulin therapy should be individualized according to blood glucose values, A1C, diet, medications, lifestyle, etc. Sliding scale insulin as monotherapy should be avoided because it does not provide adequate glucose control and can lead to hypoglycemia. Types of Insulin Rapid-acting insulin: lispro (Humalog), aspart (NovoRapid), glulisine (Apidra) Regular short-acting insulin: Humulin R, Novolin ge Toronto, Hypurin Regular Intermediate-acting (basal) insulin: NPH (Humulin N, Novolin ge NPH, Hypurin NPH) Long-acting (basal) insulin: glargine (Lantus), detemir (Levemir) Premixed insulin: Rapid acting: NovoMix 30, Humalog Mix 25 or 50; Short-acting: Humulin 30/70; Novolin ge 30/70, 40/60, or 50/50 Short-acting: Humulin 70/30, Novolin Initiate initial insulin regimen B High postprandial blood sugar A. 70/30 Oral agents (especially secretagogues, e.g., sulfonylureas) may need to be reduced. May need to stop when prandial insulin added. 7 B. Example of initial insulin regimen 1,3,5 10 units NPH or 0.1 to 0.2 units/kg at bedtime (not preferred) 7 10 units glargine or 0.1 to 0.2 units/kg once daily 10 units detemir or 0.1 to 0.2 units/kg once daily Consider insulin dose 0.3 to 0.4 units/kg/day as initial therapy in severe hyperglycemia (plasma glucose levels >13.9 mmol/l), random glucose consistently >16.7 mmol/l, or A1C >10%. 3,5 C. If glycemic goals not met (A1C >7%, depending on patient characteristics) with initial regimen, titrate insulin by 1 unit per day. 7 D. Give short-acting insulin 30 to 45 min before meal, rapid-acting insulin within 15 min before (preferred) or after meal. 7 Insulin naïve Receiving sliding scale insulin (SSI) only Receiving basal insulin with sliding scale Convert to Basal Therapy Calculate total SSI daily dose and give 50% as intermediate or long-acting insulin OR initiate initial insulin regimen B Basal-plus: Add single dose of short- or rapid-acting insulin D before one meal/day, usually evening meal A Goals not met C Decision to initiate SCHEDULED insulin therapy 1-7,A Goals not met C Eliminate SSI Insulin Calculate total SSI daily dose and add 50% to current intermediate or long-acting insulin dose High fasting, high postprandial blood sugars. Motivated patient willing to use multiple daily injections and monitor glucose. Basal-bolus: Add short- or rapid-acting insulin D before meals (3 doses/day) OR premixed insulin daily or BID (especially in elderly or those who have difficulty mixing insulin) A Copyright 2014 by Therapeutic Research Center

2 (PL Detail-Document #300128: Page 2 of 2) 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. Project Leaders in preparation of this PL Detail- Document: Neeta Bahal O Mara, Pharm.D., BCPS. Melanie Cupp, Pharm.D., BCPS References 1. Hirsch IB, Bergenstal RM, Parkin CG, et al. A realworld approach to insulin therapy in primary care practice. Clin Diabetes 2005;23: Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2006;29: Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009;32: Kirkman MS, Briscoe VJ, Clark N, et al. Diabetes in older adults: a consensus report. J Am Geriatr Soc 2012;60: Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Diabetes Care 2012;35: Mosenzon O, Raz I. Intensification of insulin therapy for type 2 diabetic patients in primary care: basalbolus regimen versus premix insulin analogs. Diabetes Care 2013;36(Suppl 2):S Canadian Diabetes Association 2013 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes 2013;37(Suppl 1):S Cite this document as follows: PL Detail-Document, Initiation and Adjustment of Insulin Regimens for Type 2 Diabetes. Pharmacist s Letter/Prescriber s Letter. January Evidence and Recommendations You Can Trust 3120 West March Lane, Stockton, CA ~ TEL (209) ~ FAX (209) Copyright 2014 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 or

3 PL Detail-Document # 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

4 (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

5 (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

6 (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 February Product monograph for Levemir. Novo Nordisk Canada Inc. Mississauga, ON L4W 5L6. December Product monograph for Lantus. Sanofi-Aventis Canada Inc. Laval, QC H7V 0A3. July U.S. Food and Drug Administration. Information regarding insulin storage and switching between products in an emergency. May 27, cm 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: 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: 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: 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: Product monograph for Humalog. Eli Lilly Canada Inc. Scarborough, ON M1N 2E8. April Product monograph for Apidra. Sanofi-Aventis Canada. Laval, QC H7V 0A3. February Product monograph for NovoRapid. Novo Nordisk Canada Inc. Mississauga, ON L4W 5L6. July European Medicines Agency. CHMP postauthorization summary of positive opinion for Toujeo. February 26, brary/summary_of_opinion/human/000309/wc pdf. (Accessed July 16, 2015). 13. Product monograph for NovoMix 30. Novo Nordisk Canada Inc. Mississauga, ON L4W 5L6. August Product monograph for Toujeo. Sanofi-Aventis Canada Inc. Laval, QC H7V 0A3. May PL Detail-Document, Comparison of Insulins and Injectable Diabetes Meds. Pharmacist s Letter/Prescriber s Letter. August Cite this document as follows: PL Detail-Document, How to Switch Insulin Products. Pharmacist s Letter/Prescriber s Letter. August Evidence and Recommendations You Can Trust 3120 West March Lane, Stockton, CA ~ TEL (209) ~ FAX (209) 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 or

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