Insulin Dosing Meranda Maley, 4 th year PharmD Candidate Florida A & M University Preceptor: Kyle Campbell, PharmD June 7, 2013
Educational Objectives 1. Discuss the insulin medications available for the management and treatment of hyperglycemia for patients with type 1 and type 2 diabetes. 2. Assess the differences between initiating and/or altering insulin regimens and dosing as it relates to efficacy, safety, hypoglycemia, cost, and patient-related factors. 3. Implement a step-wise approach via a case study to demonstrate clinical application of appropriate insulin dosing. 4. Describe the role of the pharmacist in educating patients and providers in the management of type 1 and type 2 diabetes. 2
Insulin Basics Insulin therapy mimics normal insulin secretion in the body. o Prandial and postprandial coverage o Expected decreases in A1C are highest with insulin Source: Diabetes Teaching Center at the University of California Medical Center, San Francisco. 3
Glycemic Goals in Adults AACE glycemic goals: o A1C: 6.5% o Fasting plasma glucose: <110mg/dL o 2-h plasma glucose: <140mg/dL ADA glycemic goals: o A1C: <7.0% o Preprandial glucose: <70 130mg/dL o 1-2h plasma glucose: <180 mg/dl Source: ADA. Standards of Medical Care in Diabetes. Diabetes Care. 2013;36 (Supp 1) AACE Diabetes Care Plan Guidelines, Endocr Pract. 2011;17 (Suppl 2) 4
A1C Goals Source: Canadian Diabetes Association Clinical Practice Guidelines Expert Committee, "Canadian Diabetes Association 2013 Clinical Practice Guidelines for Targets of Glycemic Control," Can J Diabetes, 37(2013): S31-S34. 5
Expected Decreases in A1C Intervention Expected Decrease in A1C (%) Metformin 1%-1.5% Sulfonylureas 1.0%-1.5% Meglinides 0.5%-1.0% Thiazolidinediones 1.0%-1.5% Alpha-Glucosidase Inhibitors 0.5%-1.0% Insulin 1.5%-3.5% GLP-1 analogs 1.0%-1.5% Amylin analogs 0.5%-1.0% DDP inhibitors 0.5%-1.0% Source: Drugs for Type 2 Diabetes. Pharmacist s Letter/Prescriber s Letter. June 2012. 6
Types of Insulin Available Rapid-acting (onset of action 5-15 min) o Apidra (Glulisine) o Humalong (Lispro) o Novolog (Aspart) Short-acting (onset of action 30-60 min) o Also known as regular human insulin Humulin R U100 Novolin R Humulin R U500* Source: Skyler JS. Therapy for Diabetes Mellitus and Related Disorders. 2004. Aventis. Apidra Prescribing Information. 2013. 7
Types of Insulin Available (continued) Intermediate Acting (onset of action 2-4 hr) o Also known as NPH human insulin Humulin N Novolin N Long-acting (onset of action 2-4 hr) o Lantus (Glargine) o Levemir (Detemir) Sources: Skyler JS. Therapy for Diabetes Mellitus and Related Disorders. 2004. Aventis. Lantus Prescribing Information. 2013. Novo Nordisk. Levemir Prescribing Information. 2013. Novo Nordisk. Novolin N Prescribing Information. 2013. Eli Lilly. Humulin N Prescribing Information. 2013. 8
Premixed Formulations Premixed insulin (onset of action: 30 60 min) o Humulin 70/30 o Humulin 50/50 o Novolin 70/30 Premixed insulin analogs (onset of action: 5 15 min) o Humalog Mix 75/25 o Humalog Mix 50/50 o NovoLog Mix 70/30 Source: Skyler JS. Therapy for Diabetes Mellitus and Related Disorders. 2004. Eli Lilly. Humalog Prescribing Information. 2013. 9
Non-Insulin Injectables These agents should not be confused with insulin: o Byetta (Exenatide) o Bydureon (Exenatide ER) o Victoza (Liraglutide) o Symlin (Pramlintide) 10
Insulin Secretion Activity Source: Diabetes Teaching Center at the University of California Medical Center, San Francisco 11
Patient Selection Eligible Patients o Type 1 diabetics o Significant hyperglycemia A1C >9% Symptomatic o Those who fail to meet oral therapy glycemic goals Initiation of insulin is preferred over adding a third oral agent in patients not meeting A1C or FPG goals 12
Recommend Therapies for T1DM ADA Guidelines: o Use of MDI injections or CSII therapy o Matching of prandial insulin to carbohydrate intake, pre-meal blood glucose, and anticipated activity o Use of insulin analogs Source: ADA. Standards of Medical Care in Diabetes. Diabetes Care. 2013;36 (Supp 1) 13
Recommend Therapies for T2DM ADA Guidelines: o o o In newly diagnosed type 2 diabetic patients with markedly symptomatic and/or elevated blood glucose levels or A1C, consider insulin therapy, with or without additional agents, from the outset. If noninsulin monotherapy at maximal tolerated dose does not achieve or maintain the A1C target over 3 6 months, add a second oral agent, a GLP-1 receptor agonist, or insulin. Due to the progressive nature of type 2 diabetes, insulin therapy is eventually indicated for many patients with type 2 diabetes. Source: ADA. Standards of Medical Care in Diabetes. Diabetes Care. 2013;36 (Supp 1) 14
Factors Affecting Treatment Patients who dislike administration method Noncompliance Carbohydrate intake o Recommended daily allowance is 130g/day Exercise o o Can cause hypoglycemia Add carbohydrate(s) prior to exercise if glucose is <100mg/dL Hypoglycemia unawareness Co-morbidities 15
Start low and go slow. Insulin therapy is always individualized. Several algorithms are available. AACE recommendations: o o o Initiating Insulin Treatment Long-acting insulin should be the initial choice in most cases NPH insulin Rapid-acting insulin Source: AACE Diabetes Care Plan Guidelines, Endocr Pract. 2011;17 (Suppl 2) 16
Initiating Premixed Insulin Premixed insulins are a less favorable option o Provide postprandial and intermediate release glucose control o Considered for patients in whom adherence is an issue o Disadvantages: Lack flexibility of titration Limited ability to reach glycemic targets May increase the risk for hypoglycemia compared with basal insulin or basal-bolus insulin Source: AACE Diabetes Care Plan Guidelines, Endocr Pract. 2011;17 (Suppl 2) 17
Beginning Insulin Therapy Normally 10-20 units daily or 0.1 to 0.2 units/kg/day o Varies depending on patient s A1C Long-acting OR intermediate insulin is preferred When patient fails to achieve glycemic goals: o Add rapid-acting insulin before meals 18
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Calculating Insulin Dose CHO to insulin ratios vary with each patient o Is your patient type 1 or type 2? Total Daily Dose (TDD) will vary o Sensitivity and resistance is important o Initially your best guess 21
Long-Acting Dosing Detemir and Glargine 22
Lantus (Glargine) May be administered at any time during the day, at the same time every day. Do NOT administer via insulin pumps Type 1 o Approximately one-third of the total daily dose o Short-acting insulin should be used concurrently Type 2 o 10 units (or 0.2 units/kg) once daily Source: Product information for Lantus. Sanofi-Aventis U.S. LLC. Bridgewater, NJ 08807. March 2013 23
Lantus (Glargine) (continued) Source: Product information for Lantus. Sanofi-Aventis U.S. LLC. Bridgewater, NJ 08807. March 2013 24
Levemir (Detemir) Administered once or twice daily o Once daily dosing should be administered with the evening meal or at bed time. o Patients who require twice daily dosing can administer insulin in the morning and at bed time. 12-hour spacing recommended Source: Product information for Levemir. Novo Nordisk Inc. Princeton, NJ 08540. March 2013 25
Type 1 o Approximately one-third of the total daily dose o MUST be used in a regimen with rapid-acting or shortacting insulin Type 2 Levemir (Detemir) (continued) o The starting dose is 10 units (or 0.1-0.2 units/kg) given once daily in the evening or divided into a twice daily regimen Source: Product information for Levemir. Novo Nordisk Inc. Princeton, NJ 08540. March 2013 26
Intermediate Dosing Humulin N and Novolin N 27
Intermediate-Acting Insulin Humulin N and Novolin N o Type 1 Individualized dosing Once or twice daily injections o Type 2 Initial: 0.1-0.2 units/kg/day once or twice daily May be used in combination with noninsulin agents Source: Micromedex Healthcare Series [intranet database]. Version 1.48.0b1705. Greenwood Village, Colo: Thomson Healthcare. 28
Short-Acting Dosing Humulin R and Novolin R 29
Humulin R U-100 Novolin R Individualized dosing o Initiation: 0.5-1.0 unit/kg/day Dosing is the same in type 1 and type 2 Source: Micromedex Healthcare Series [intranet database]. Version 1.48.0b1705. Greenwood Village, Colo: Thomson Healthcare. 30
Humulin R U-500 Not a short-acting insulin Concentrated o 5-times more concentrated than Humulin R U-100 Useful for insulin-resistant patients requiring >200 units daily o Can be used in type 1 and type 2 diabetics Dosing confusion/errors o Dispensing o Prescribing o Administration Source: Product information for Humulin R U-500. Lilly USA, LLC, Indianapolis, IN 46285. March 2013 31
Humulin R U-500 Dosing Average TDD requirement for maintenance therapy in patients without severe insulin resistance lies between 0.5-1.0 unit/kg/day. o May be substantially higher in some incidences Usually given two or three times daily before meals. o Within approximately 30 minutes of administration Source: Product information for Humulin R U-500. Lilly USA, LLC, Indianapolis, IN 46285. March 2013 32
Algorithm for Insulin Therapy Based on TDD Source: American Heart Association. Diabetes Care, The Use of U-500 in Patients With Extreme Insulin Resistance. Volume 28, Number 5, May 2005 33
Source: Product information for Humulin R U-500. Lilly USA, LLC, Indianapolis, IN 46285. March 2013 34
Key Differences Humulin R U-500 Humulin R U-100 500 units/ml Duration of action: up to 24 hours Prescription Administration: SC only Cost: $219.46 per vial 100 units/ml Duration of action: 4-12 hours (may increase with dose) Non-prescription Administration: SC, IM, IV (unlabeled) Cost: $36.19 per vial Source: Comparison of Insulins. Pharmacist s Letter/Presriber s Letter 2006; 22(9):220910. 35
Rapid-Acting Dosing Aspart, Glulisine, and Lispro 36
Novolog (Aspart) The TDD varies between 0.5 to 1.0 units/kg/day o 50 to 70% of TDD o The remaining insulin requirements are provided by an intermediate-acting or long-acting insulin. o Administer immediately (within 5-10 minutes) before a meal. Source: Product information for Novolog. Novo Nordisk Pharmaceuticals. Princeton, NJ 08540. March 2013 37
Apidra (Glulisine) The TDD varies between 0.5 to 1.0 units/kg/day o Administer within 15 minutes before a meal OR within 20 minutes after a meal. o This is used with long-acting or intermediate-acting regimens. Source: Aventis. Apidra Prescribing Information. 2013 38
Humalog (Lispro) The TDD varies between 0.5 to 1.0 units/kg/day o Administer within 15 minutes before a meal OR within 20 minutes after a meal. o This is used with long-acting or intermediate-acting regimens. Source: Eli Lily and Company. Humalog package insert. Indianapolis, IN: 2013. 39
Additional Considerations Basal-Bolus Regimens Sliding Scale 40
Basal-Bolus Insulin Therapy Include 4 injections daily Allows for flexibility o Varied food intake or irregular meal patterns o Can adjust insulin doses at each meal Initiation of pre-meal prandial insulin doses: o 5 units per meal o 7% of the basal insulin dose o 1 unit per 15 g carbohydrate Source: AACE Diabetes Care Plan Guidelines, Endocr Pract. 2011;17 (Suppl 2) 41
Sliding Scale Dosing Inpatient setting is preferred Doses are determined by the physician-based desired glycemic goals For additional information, reference individual hospital protocols 42
Sliding Scale Regimen Example Source: http://diabetesinstitute.pitt.edu/files/reghumuliniss.pdf 43
Designing an Insulin Regimen Points to consider: o o o o Switching from oral agents to insulin Mixing insulin products Switching insulin products Insulin pumps 44
Switching Oral to Insulin Choose an insulin that fits your patient best Units administered are determined by body weight o Start with 0.1-0.2units/kg/daily, higher in some cases There is no conversion from an oral dose to insulin units o For example: mcg or mg units 45
Choosing Insulin Agents How do you know what insulin to use? o Long-acting insulin No peak Less weight gain Less nocturnal hypoglycemia o NPH insulin Cost advantage o Rapid-acting insulin Shown to be more effective in lowering postprandial glucose Lower risk of hypoglycemia Provides flexibility Predictable Source: AACE Diabetes Care Plan Guidelines, Endocr Pract. 2011;17 (Suppl 2) 46
Mixing insulin products Rapid- and short-acting are CLEAR Intermediate-acting is CLOUDY o Draw up the clear insulin first, then draw up the cloudy insulin. Long-acting is CLEAR o Although Lantus and Levemir are clear, they cannot be mixed with any other types of insulin. Source: Wollenburg, Pam. Your Guide To Understanding Diabetes Management. 2. Lincoln, NE: HERC Publishing, 2010. 37. Print. 47
How to Switch Between Insulin Products Converted unit-per-unit Determined by clinical scenario Source: How to switch between insulin products. Pharmacist s Letter/Presriber s Letter 2009; 25(10):251005. 48
Switching Insulin Products Source: How to switch between insulin products. Pharmacist s Letter/Presriber s Letter 2009; 25(10):251005 49
Switching Insulin Products (continued) Source: How to switch between insulin products. Pharmacist s Letter/Presriber s Letter 2009; 25(10):251005 50
Advantages: o Eliminates individual insulin injections o Results in fewer fluctuations in blood glucose levels o Helps to improve quality of life Disadvantages: o Expensive Insulin Pumps o Bothered by attached device o Can cause ketoacidosis (DKA) if the catheter comes out Source: American Diabetes Association. (2013) Living With Diabetes. <http://www.diabetes.org/living-with-diabetes/treatment-andcare/medication/insulin/advantages-of-using-an.html> 51
Insulin Pumps Provides a reservoir of insulin o Continuous delivery of basal insulin o Delivers bolus when needed (i.e., eating) Additional Information: o American Diabetes Association: http://forecast.diabetes.org/consumerguide/charts o Animas Corporation: www.animas.com Source: American Diabetes Association. (2013) Living With Diabetes. <http://www.diabetes.org/living-with-diabetes/treatmentand-care/medication/insulin/advantages-of-using-an.html> 52
Pharmacist Education 53
Diabetic Supplies When choosing needles, please consider: o o Length (mm) Patients with a greater body mass index (BMI) will require longer needles. Shorter needles provide a greater comfort to patients. Gauge (G) The higher the gauge, the thinner the needle. Source: BD and BD Logo are trademarks of Becton, Dickinson and Company 54
Diabetic Supplies When choosing a syringe, please consider: o Volume (ml/cc) How much insulin is the patient injecting? Source: BD and BD Logo are trademarks of Becton, Dickinson and Company 55
Diabetic Supplies When selecting testing strips, please consider: o Cost What does their insurance cover? o Quantity How often is the patient instructed to test their glucose? o Patient savings programs FreeStyle Promise Program Contour Choice Program One Touch Verio Test Strips 56
Blood Glucose Meters: o Points to consider: What features will be the most beneficial to the patient? GLOOKO Diabetic Supplies Large Displays Sample Size Coding Source: Life First One Touch. (2013) LifeScan Inc. Milpitas, CA 95035 Portability Color 57
Pharmacist Education Additional information: o Becton Dickinson (BD) manufacturer Pharmacists: Provides free patient samples & starter kits Continuing education programs https://forms.bd.com/retailpharmacists/index.sp Patients & Pharmacists Patient education literature Patient Insulin Syringe Assistant Program» Toll Free:1-866-818-6906 58
Pharmacist Education Drug-Induced Hyperglycemia o Antibiotics (i.e., fluroquinolones) o Antipsychotics o Beta Blockers Exception carvedilol and nebivolol o Corticosteroids o Calcineurin inhibitors o Protease inhibitors o Statins o Thiazides/thiazide-like diuretics Source: Rehman, A, S Setter, and M Vue. "Drug-Induced Glucose Alterations Part 2: Drug- Induced." Diabetes Spectrum 24.4 (2011): 234-238. Web. 19 May 2013. 59
Patient Counseling Points General self-care o o o o o Testing blood glucose regularly Hypoglycemia & hyperglycemia awareness Injection sites Foot care Exercise 150 min/week of moderate intensity aerobic activities Nutrition Carbohydrate, protein, vegetables/fruits Do not skip meals Portion control Maintaining a healthy weight Source: ADA. Standards of Medical Care in Diabetes. Diabetes Care. 2013;36 (Supp 1) 60
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Partnering with Patients Continuum of care o Provide ongoing education and support o Optimize SMBG training and adherence o Help address potential barriers Source: Life First One Touch. (2013) LifeScan Inc. Milpitas, CA 95035 62
Case Study 1: T2DM New Onset LJ is a 67 year-old female who presents to her primary care physician after her gynecologist recently diagnosed her with polycystic ovarian syndrome (PCOS) during an evaluation for amenorrhea. She complains of increasing fatigue, which she attributes to being overweight. She states her last appointment with her PCP was over 2 years ago. PMH: o o o PCOS 2 months Hyperlipidemia 2 years (diet-controlled) HTN 4 years Medications: o o Ortho-Novum 1/35 as directed Hydrochlorothiazide 50 mg po daily Source: Koehler, J, and T Schwinghammer. "Type 2 Diabetes Mellitus: New Onset." Pharmacotherapy Casebook: A Patient-focused Approach. New York, NY: McGraw-Hill Medical, 2009. 201-203. Print. 63
Case Study 1 (continued) ROS: Frequent fatigue. Occasional polydipsia, polyphagia, weakness, and lightheadedness upon standing. Denies blurred vision, chest pain, dyspnea, tachycardia, dizziness, or tingling or numbness in extremities, leg cramps, peripheral edema, changes in bowel movements, GI bloating or pain, nausea or vomiting, urinary incontinence, or presence of skin lesions. Physical exam: o o o Gen: African-American woman with central obesity in no apparent distress VS: BP 152/88 sitting R arm, BP 130/70 standing R arm, P 82, RR 18, T 37.2 C; Wt 95.5 kg, Ht 5'6'' Skin: Dry with poor skin turgor; no ulcers or rash SourcceKoehler, J, and T Schwinghammer. "Type 2 Diabetes Mellitus: New Onset." Pharmacotherapy Casebook: A Patient-focused Approach. New York, NY: McGraw-Hill Medical, 2009. 201-203. Print. 64
Case Study 1 (continued) Labs Na 141 meq/l K 4.0 meq/l Cl 96 meq/l CO2 22 meq/l BUN 16 mg/dl SCr 1.2 mg/dl Random Glu 280 mg/dl Reference Range 135-145 meq/l 3.5-5.5 meq/l 97-110 meq/l 22-30 meq/l 8-25 mg/dl 0.6-1.2 mg/dl < 200 mg/dl ( ) ketones, ( ) protein, ( ) microalbuminuria Clinical Course: The patient returned to clinic 3 days later for lab work, which revealed: FBG 189 mg/dl; A1C 9.4%; FLP: T. chol 263 mg/dl, HDL 31 mg/dl, LDL 152 mg/dl, Trig 260 mg/dl. Source: Koehler, J, and T Schwinghammer. "Type 2 Diabetes Mellitus: New Onset." Pharmacotherapy Casebook: A Patientfocused Approach. New York, NY: McGraw-Hill Medical, 2009. 201-203. Print. 65
Case Study 1 (continued) What diabetic medication(s) would you recommend? Consider LJ s presenting symptoms and labs. Would you start oral or insulin therapy first? Both? Why? Louise Jackson 6/7/13 123 ABC Drive 01/01/46 Dr. Smith 66
Case Study 2: T2DM Existing Disease A patient presents to you with the following prescription. She indicates that her physician stated increase your daily units as needed, however she is unclear how to do so. How would you counsel this patient? Jane Doe 6/7/13 123 ABC Drive 01/01/50 Humalog 100units/mL 10 units SC at breakfast, lunch, and dinner Dr. Smith 67
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Acknowledgement Thank You, Doreen Inman, PharmD, MBA, BCPS,CDE for your guidance and review! 69
Medicare Quality Improvement Organizations are a change agent and convener for widespread, significant improvements in health quality. This material was prepared by FMQAI, the Medicare Quality Improvement Organization for Florida, under contract with the Centers for Medicare & Medicaid Services (CMS), an agency of the Department of Health and Human Services (HHS). The contents presented do not necessarily reflect CMS policy. FL-10SOW-2013FLC705-6-971 70
References 1. ADA. Standards of Medical Care in Diabetes. Diabetes Care. 2013;36 (Supp 1) 2. AACE Diabetes Care Plan Guidelines, Endocr Pract. 2011;17(Suppl 2) 3. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee, "Canadian Diabetes Association 2013 Clinical Practice Guidelines for Targets of Glycemic Control," Can J Diabetes, 37(2013): S31-S34. 4. Drugs for Type 2 Diabetes. Pharmacist sletter/prescriber s Letter. June 2012. 5. Skyler JS. Therapy for Diabetes Mellitus and Related Disorders. 2004. 6. Aventis. Apidra Prescribing Information. 2013. 7. Aventis. Lantus Prescribing Information. 2013. 8. Novo Nordisk. Levemir Prescribing Information. 2013. 9. Novo Nordisk. Novolin N Prescribing Information. 2013. 10. Eli Lilly. Humulin N Prescribing Information. 2013. 11. Eli Lilly. Humalog Prescribing Information. 2013. 12. Product information for Humulin R U-500. Lilly USA, LLC, Indianapolis, IN 46285. March 2013 13. Micromedex Healthcare Series [intranet database]. Version 1.48.0b1705. Greenwood Village, Colo: Thomson Healthcare. 14. American Heart Association. Diabetes Care, The Use of U-500 in Patients With Extreme Insulin Resistance. Volume 28, Number 5, May 2005 15. Comparison of Insulins. Pharmacist s Letter/Presriber s letter 2006; 22(9):220910. 16. Wollenburg, Pam. Your Guide To Understanding Diabetes Management. 2. Lincoln, NE: HERC Publishing, 2010. 37. Print. 17. How to switch between insulin products. Pharmacist s Letter/Presriber s Letter 2009; 25(10):251005. 18. American Diabetes Association. (2013) Living With Diabetes. http://www.diabetes.org/living-with-diabetes/treatment-andcare/medication/insulin/advantages-of-using-an.html 19. BD and BD Logo are trademarks of Becton, Dickinson and Company 20. Life First One Touch. (2013) LifeScan Inc. Milpitas, CA 95035 21. Rehman, A, S Setter, and M Vue. "Drug-Induced Glucose Alterations Part 2: Drug-Induced." Diabetes Spectrum 24.4 (2011): 234-238. Web. 19 May 2013. 22. Koehler, J, and T Schwinghammer. "Type 2 Diabetes Mellitus: New Onset." Pharmacotherapy Casebook: A Patient-focused Approach. New York, NY: McGraw-Hill Medical, 2009. 201-203. Print. 71