Initiation and Adjustment of Insulin Regimens for Type 2 Diabetes

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PHARMACIST’S LETTER / PRESCRIBER’S LETTER

January 2014

3120 W. March Lane, Stockton, CA 95219 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.PharmacistsLetter.com ~ www.PrescribersLetter.com ~ www.PharmacyTechniciansLetter.com Initiate initial insulin regimen^B

High postprandial blood sugar

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

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.

A. 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 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 70/30

Insulin naïve Receiving sliding scale insulin (SSI) only Receiving basal insulin with sliding scale

High fasting, high postprandial blood sugars.

Motivated patient willing to use multiple daily injections and monitor glucose.

Convert to Basal Therapy

Calculate total SSI daily dose and give 50% as intermediate or long-acting insulin OR initiate initial insulin regimen^B

Eliminate SSI Insulin

Calculate total SSI daily dose and add 50% to current intermediate or long-acting insulin dose

Goals not met^C

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

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(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 real- world approach to insulin therapy in primary care practice. Clin Diabetes 2005;23:78-86.

2. 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;29:1963-72.

3. 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;32:193-203.

4. Kirkman MS, Briscoe VJ, Clark N, et al. Diabetes in older adults: a consensus report. J Am Geriatr Soc 2012;60:2342-56.

5. Inzucchi SE, Bergenstal RM, Buse JB, et al.

Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Diabetes Care 2012;35:1364-79.

6. Mosenzon O, Raz I. Intensification of insulin therapy for type 2 diabetic patients in primary care: basal- bolus regimen versus premix insulin analogs.

Diabetes Care 2013;36(Suppl 2):S212-8.

7. Canadian Diabetes Association 2013 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes 2013;37(Suppl 1):S1-212.

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 2014.

Evidence and Recommendations You Can Trust…

3120 West March Lane, Stockton, CA 95219 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249 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 www.PharmacistsLetter.com,

www.PrescribersLetter.com, or www.PharmacyTechniciansLetter.com

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PHARMACIST’S LETTER / PRESCRIBER’S LETTER

August 2015

3120 W. March Lane, Stockton, CA 95219 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.PharmacistsLetter.com ~ www.PrescribersLetter.com ~ www.PharmacyTechniciansLetter.com

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

 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

Long-acting to NPH

Insulin detemir (Levemir) to NPH  Convert unit-per-unit.⁴

 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.⁴No 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

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Long-acting to long-acting, continued Insulin detemir (Levemir) to insulin glargine (Toujeo)

 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

 Do not mix insulin glargine with other insulins.¹⁴ Insulin glargine (Lantus) to insulin glargine

(Toujeo)

 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

 Do not mix insulin glargine with other insulins.¹⁴ Insulin glargine (Lantus) to insulin detemir

(Levemir)

 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 Insulin glargine (Toujeo) to insulin glargine

(Lantus) or insulin detemir (Levemir)

 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.

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])

 Convert unit-per-unit.^4,9-11

 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 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

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)

 See Comparison of Insulins and Injectable Diabetes Meds for specifics of meal timing.

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Premixed to premixed

Premixed NPH/regular insulin (Humulin 30/70, Novolin ge 30/70) to premixed protamine/rapid- acting analog (insulin lispro protamine/insulin lispro [Humalog Mix 25], insulin aspart protamine/insulin aspart [NovoMix 30])

 Convert unit-per-unit.^4,9,13

 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

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)

 Convert unit-per-unit.⁴

 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

Premixed NPH/regular insulin (Novolin ge 50/50) to premixed insulin lispro protamine/insulin lispro (Humalog Mix 50)

 Convert unit-per-unit.^4,9

 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

Premixed insulin lispro protamine/insulin lispro (Humalog Mix 50) to premixed NPH/regular insulin (Novolin ge 50/50)

 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

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)

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.

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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 post- authorization 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