Intensifying Insulin Therapy

Transcription

1 Intensifying Insulin Therapy Rick Hess, PharmD, CDE, BC-ADM Associate Professor Gatton College of Pharmacy, Department of Pharmacy Practice East Tennessee State University Johnson City, Tennessee Learning Objectives Name barriers to insulin intensification Describe advantages and disadvantages to premixed and basal bolus insulin therapy Calculate an insulin-to-carb ratio (ICR) and insulin sensitivity factor (ISF) based on patient case Describe the appropriate use of U500 insulin in patients with severe insulin resistance Insulin Initiation and Dose Adjustment There is no one perfect insulin regimen for either Type 1 or Type 2 diabetes (hence the different regimens used across the globe) There are a number of simple principles which can guide insulin initiation but an individual s response cannot be predicted Similarly for dose adjustment one can follow simplified guidelines but these must be modified depending on an individual s response Ira Hirsch, MD Page 1

2 Patient Case Ms. Johnson is a 58 year old with an A1c of 8.5% and is on: Insulin glargine 60 units at bedtime Metformin 1000mg twice daily Glimepiride 4mg twice daily All other labs WNL Physical and Chemical Properties of Human Insulin α-chain β-chain 21 amino acids 30 amino acids Monomers Dimers Self-aggregation in solution Zn ++ Zn ++ Hexamers (around Zn 2+ ) Insulin Comparison Basal Insulin Agent Onset (h) Peak (h) Duration (h) Considerations NPH Greater risk of nocturnal hypoglycemia vs. insulin analogues Glargine No pronounced Up to 24 ~1-4 Detemir peak* hours Less nocturnal hypoglycemia vs.nph Bolus Insulin Agent Onset (h) Peak (h) Duration (h) Considerations Regular ~0.5-1 ~2-3 Up to 8 Aspart Glulisine <0.5 ~ ~3-5 Lispro * Exhibits a peak at higher dosages. Dose-dependent. Inject min before a meal; Injection with or after a meal could increase risk for hypoglycemia Inject 0-15 min before a meal; Less risk of postprandial hypoglycemia vs. regular insulin Endocr Pract. 2013;Feb 20:1-33. [Epub ahead of print]. Page 2

3 Summary of Action Profiles of Injected Modified Human Insulin and Insulin Analogues Plasma insulin levels Aspart, glulisine, lispro 4 6 hours Regular 6 8 hours NPH hours Glargine, detemir ~24 hours Hours Insulin Resistance Patient resistance Fear of needles Fear of hypoglycemia Fear of medication dependency Fear of weight gain Delayed insulin initiation Retrospective, observational data Average ~5 years of A1c > 8% before initiation Average ~10 years of A1c > 7% before initiation Diabetes Care 2005; 28; Diabetes Care 2004; 27; Provider Resistance to Initiating Effective Diabetes Therapy GP I prefer to delay initiation of oral therapy until absolutely essential I prefer to delay initiation of insulin until absolutely essential 23% 68% Specialist MD 10% 34% Nurse 32% 46% US HCPs agreeing (%) Diabetes Care 2005; 28; Page 3

4 Insulin Therapy: An Ongoing Process Primary care provider roles Set individualized A1c goal Initiate insulin therapy Titrate to glycemic target(s) Intensify insulin if target not achieved Refer to specialist and/or CDE Requires frequent contact Diabetes Care Aug;36 Suppl 2:S212-8 Insulin Strategies for T2DM Diabetes Care Jun;35(6): Simple Basal Insulin Once daily (usually) Start at ~0.2 units/kg/day Preferred when adding to oral agents Treat-to-target strategies available Fasting Glucose (mg/dl) Basal Dose Adjustment units units units > units How long do I keep increasing the dose? Diabetes Care Aug;36 Suppl 2:S212-8 Diabetes Care. 2003; 26(11): Page 4

5 Insulin Intensification: Pre-Mixed Insulin or Basal Bolus? Pre-Mix Preferred Patient preference Older age Assistance required with injections Organized lifestyle Eats twice daily or evening main meal Basal Bolus Preferred All T1DM patients Younger age High motivation and adherence Active lifestyle High variability in nutritional patterns or habits Diabetes Care Aug;36 Suppl 2:S212-8 Converting to Pre-Mixed Insulin FBG acceptable, but A1c > 7% on basal alone If converting from basal insulin to pre-mix twice daily: Divide TDD in half and give before breakfast and supper Initiate hours after last basal insulin dose Examples Humulin 70/30 [70% NPH, 30% Regular] Novolin 70/30 [70% NPH, 30% Regular] Humalog Mix 75/25 [75% lispro protamine, 25% lispro] Humalog Mix 50/50 [50% lispro protamine, 50% lispro] Novolog Mix 70/30 [70% aspart protamine, 30% aspart] Pre-Mix Insulin Titration FBG (mg/dl) Adjustment for pre-supper dose Pre-dinner (mg/dl) Adjustment for pre- BFAST dose > units > units units units units units No change No change units units < 60-4 units or as appropriate < 60-4 units or as appropriate Ann Intern Med 2006;145: Page 5

6 The Basal/Bolus Insulin Concept Most physiologic insulin supplementation strategy Basal insulin Suppresses glucose production between meals and overnight ~ 40% to 50% of daily needs Bolus insulin Limits hyperglycemia after meals Immediate rise and sharp peak at 1 hour ~ 10% to 20% of total daily insulin requirement at each meal Normal Physiologic Insulin Secretion The Basal/Bolus Concept B L D HS This is NOT Basal Bolus Page 6

7 Easing Into Insulin Intensification If adding bolus at largest meal to existing basal insulin: Give bolus at 10% of TDD and reduce basal insulin dose by 10% Diabetes Metab Res Rev. 2007;23(4): Optimizing Basal Bolus Therapy Establishing Starting Basal and Bolus Dosing Based on Carb Counting and Pre-Meal Readings Determine Insulin Carb Ratio and Insulin Sensitivity Factor Total Daily Dose Split to mimic Euglycemic control ~ 50% Basal ~ 50% Bolus Insulin to Carbohydrate Ratio (ICR) RH is receiving insulin detemir 13 units twice daily & insulin aspart 8 units before meals. Last A1c was 8% and most 2hr PPG > 200mg/dl. Occasional hypoglycemia reported. 500 Rule = 500/TDD Example: 500/50 units = 10 1 unit of BOLUS insulin per 10g of carbohydrates 4oz cornbread = ~ 50g = units? 1 cup soup beans = ~ 40g = units? 32oz Pal s sweet tea = ~ 52g = units? Page 7

8 Insulin Sensitivity Factor (ISF) RH s bedtime BG ranges from mg/dl. He wants to know if he can give some extra insulin detemir at bedtime. Rapid acting analog insulin 1800 Rule: 1800/TDD Example: 1800/50 units = 36mg/dl 1 unit of rapid acting BOLUS insulin will drop sugar ~36mg/dl Short acting human insulin 1500 Rule: 1500/TDD Example: 1500/50 units = 30mg/dl 1 unit of short acting BOLUS insulin will drop sugar ~30mg/dl Insulin Intensification Algorithm START BASAL (long-acting insulin) INTENSIFY (prandial control) A1c < 8% A1c > 8% Add GLP-1 RA or DPP4-i Add Prandial Insulin TDD TDD TDD: U/kg U/kg U/kg 50% Basal Analog 50% Prandial Analog Insulin titration every 2 3 days to Less desirable: NPH reach glycemic goal: and regular insulin or Fixed regimen: Increase TDDby 2 U Glycemic Control premixed insulin Adjustable regimen: FBG > 180 mg/dl: add 4 U Not at Goal** FBG mg/dl: add 2 U FBG mg/dl: add 1 U If hypoglycemia, reduce TDD by: Insulin titration every 2 3 days to reach glycemic goal: BG < 70 mg/dl: 10% 20% Increase basaltddas follows: BG < 40 mg/dl: 20% 40% Fixed regimen: Increase TDDby 2 U Adjustable regimen: FBG > 180 mg/dl: add 4 U Consider discontinuing or reducing sulfonylurea after FBG mg/dl: add 2 U basal insulin started (basal analogs preferred to NPH) FBG mg/dl: add 1 U Increase prandial dose by 10% for any meal if the 2-hr postprandial or next premeal glucose is > 180 mg/dl ** Glycemic Goal: Premixed: Increase TDD by 10% if fasting/premeal For most patients with T2D, an A1c < 7%, fasting and BG > 180 mg/dl premeal BG < 110 mg/dl in the absence of hypoglycemia. If fasting AM hypoglycemia, reduce basal insulin A1c and FBG targets may be adjusted based on patient s If nighttime hypoglycemia, reduce basal and/or pre-supper age, duration of diabetes, presence of comorbidities, or pre-evening snack short/rapid-acting insulin diabetic complications, and hypoglycemia risk. If between meal daytime hypoglycemia, reduce previous premeal short/rapid-acting insulin Copyright 2013 AACE Maynot be reproduced inanyform withoutexpresswritten permissionfrom AACE. Reprinted with permission from American Association of Clinical Endocrinologists. Endocr Pract. 2013;19: Insulin Dose Titration Summary Target glucose excursion based on pattern management Adjust: Morning short or rapid acting insulin Morning NPH insulin or pre-lunch short or rapid acting insulin Pre-dinner short or rapid acting Pre-dinner NPH or bedtime basal insulin Based on: Pre-lunch blood glucose Pre-dinner blood glucose Bedtime blood glucose Morning (fasting) blood glucose Page 8

9 Frequency of Severe Hypoglycemia With Antihyperglycemic Agents Percentage of Patients Treated in 1 Year 6% Mixtures, Rapid-acting, Basal-bolus 5% 4% Basal Insulin 3% 2% 1% 0 Sulfonylureas Meglinitides DPP-4 inhibitors, GLP-1 receptor agonists, Metformin, TZDs Endocr Pract. 2013;Feb 20:1-33. [Epub ahead of print]. Basal Bolus Insulin Advantages More precise dosing Carb loads Correction Flexible dosing Irregular schedules Exercise Better control (i.e., A1c < 7%) vs. pre-mix insulin Cost Disadvantages Increased hypoglycemia risk Complex regimen and dosing Greater number of injections Weight gain Cost Diabetes Care Jun;35(6): Cleve Clin J Med May;78(5): Severe Insulin Resistance Humulin R U500 (Concentrated) Onset min Peak 2 4 hours Duration 6 8 hours Recommended in patients requiring TDD > 200 units/day Conversion dosing: TDD x 80% 5 Example: 300 units x 80% = 240 units 5 = 48 units or 0.48ml (total daily volume) Page 9

10 Measuring U500 Accessed September 13th 2014 U500 Dosing and Titration TDD (units) Frequency Dosage BID (am/pm) 50/50 or 60/40 before breakfast and supper TID 33/33/33 before meals Pump Three mealtime bolus doses = 50% TDD plus 24-hr basal insulin infusion = 50% TDD TID 33/33/33 before meals QID 30/30/30/10 (mealtimes and bedtime) Pump Three mealtime bolus doses = 50% TDD plus 24-hr basal insulin infusion = 50% TDD > 600 QID 30/30/30/10 (mealtimes and bedtime) Am J Health Syst Pharm. 2010;67(18): In the Pipeline FDA approved, expected availability 2015 Inhaled regular insulin (Afrezza) Phase 3/Pending approval Insulin glargine (300 units/ml) (Toujeo) Insulin degludec (100 and 200 units/ml) (Tresbia) Insulin degludec/liraglutide (Xultophy) Insulin degludec/aspart (Ryzodeg) Insulin peglispro Biosimilar Insulin Insulin glargine (Basaglar) Page 10

11 Questions? Page 11