Case Vignette for Question 5

Size: px

Start display at page:

Download "Case Vignette for Question 5"

Mildred Johnson
7 years ago
Views:

1 Question 5: What are the options for intensifying therapy when basal insulin has not achieved target glycemia? Case Vignette for Question 5 64-year-old man with 9-year history of T2DM Current diabetes medications: Metformin 2000 mg daily Insulin glargine U U QD HbA1c initially declined but now has increased to 7.8% FPG averages about 120 mg/dl PPG levels elevated especially after evening meal Weight=212 lbs, height 5 10 (BMI=30.4 kg/m2) What should be the next step? 2 1

2 What should be the next step? 1. Increase glargine U-100 dose 2. Switch to premixed insulin 3. Add SGLT2 inhibitor 4. Add a DPP-4 inhibitor 5. Add a GLP-1 RA 6. Add rapid acting prandial insulin 7. Add inhaled insulin 3 ADA/EASD Position Statement Options when Basal Insulin +/- OADs Don t Achieve Target Glycemia 2 Add 1 rapid insulin injection before largest meal If not controlled after FBG target is reached (or if dose >0.5 U/kg/day), treat PPG excursions with mealtime insulin. (Consider initial GLP-1-RA trial) Change to premixed insulin twice daily mod. Start: 4 U, 0.1 U/kg or 10% basal dose. If HbA1c<8%, consider ibasal by same amount Start: Divide current basal dose into 2/3 AM, 1/3 PM or 1/2 AM, 1/2 PM Adjust: hdose by 1 2 U or 10 15% oncetwice weekly until SMBG target reached. Adjust: hdose by 1 2 U or 10 15% oncetwice weekly until SMBG target reached. For hypo: Determine and address cause; icorresponding dose by 2 4 U or 10 20% For hypo: Determine and address cause; icorresponding dose by 2 4 U or 10 20% 3+ If not controlled, consider basalbolus Add 2 rapid insulin injections before meals ( basal bolus ) If not controlled, consider basalbolus high Start: 4 U, 0.1 U/kg or 10% basal dose/meal. If HbA1c<8%, consider ibasal by same amount Adjust: hdose by 1 2 U or 10 15% once-twice weekly until SMBG target reached. For hypo: Determine and address cause; icorresponding dose by 2 4 U or 10 20% Flexibility more flexible less flexible Inzucchi SE, et al. Diabetes Care. 2015;38:

Garber AJ, et al. Endocr Pract. 2016;22(1):84 113. Used for Educational Purposes Only.

3 Garber AJ, et al. Endocr Pract. 2016;22(1): Used for Educational Purposes Only. 5 Use of GLP-1 RAs in Combination with Insulin Study 24-week RCT 1 (N=124) 26-week RCT 2 (N=177) Background Insulin Therapy GLP-1 RA HbA1c Reduction (mean, %) Change in Basal Insulin Dose Weight Change (kg) Basal bolus Liraglutide U 2.4 Degludec Liraglutide vs lispro QD 0.74 vs 0.39 p = NR -2.8 kg +0.9 kg p < week RCT 3 (N=627) 26-week RCT 4 (N=563) 30-week RCT 5 (N=261) Glargine U-100 (mean 61 U/day at randomization) Glargine U-100 Glargine U-100 Exenatide µg/day vs lispro tid Albiglutide weekly vs lispro tid Exenatide 10 µg BID 1.13 vs 1.10 NR -2.5 vs +2.1 p < vs 0.66 p < p < to 53 U vs 44 to 51 U +13 vs +20 U in placebo group vs vs Lind M, et al. BMJ. 2015;351:h Mathieu C, et al. Diabetes Obes Metab. 2014;16: Diamant M, et al. Diabetes Care. 2014;37: Rosenstock J, et al. Diabetes Care. 2014;37: Buse JB, et al. Ann Intern Med. 2011;154:

4 DPP-4 Inhibitors plus Basal Insulin 1 Study 26-week RCT 2 (N=390) 24-week RCT 3 (N=651) DPP-4 Inhibitor Insulin Insulin + DPP-4 Inhibitor Change HbA1c (mean, %) Alogliptin Various (12.5 mg) (25 mg) Sitagliptin Long-acting, intermediateacting or premixed 24-week RCT Linagliptin Glargine U-100, (N=1261) 4 Detemir, or NPH insulin (28-week) extension of a short-term (24-week) 5 Insulin Change HbA1c (mean, %) Saxagliptin Various Ahluwalia R, Vora J. Diabetes Ther. 2011;2(3): Rosenstock J et al. Diabetes Obes Metab. 2009;11: Vilsbøll T, et al. DiabetesObes Metab. 2010;12: Tradjenta (linagliptin) tablets [package insert], Boehringer Ingelheim Pharmaceuticals, Inc./Eli Lilly: Barnett AH, et al. Clin Drug Investig. 2013;Oct;33(10): Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors in T2DM with Insulin Study SGLT2 Inhibitor Insulin Insulin + SGLT2 Inhibitor Change HbA1c (mean, %) 24-week RCT 1 (N=800) 18-week RCT 2 (N=1708) 78-week RCT 3 (N=494) Dapagliflozin (2.5, 5, or 10 mg) Canaglifozin (100 mg, 300 mg) Empagliflozin (10 or 25 mg) Various to Various Glargine U-100, Detemir, NPH (100 mg) (300 mg) p<0.001 for both -0.3% (10 mg) -0.5% (25 mg) p<0.001 for both 1. Wilding JP, et al. Ann Intern Med. 2012;156(6): Matthews DR, et al. Abstract 764. Diabetologia. 2012;55(Suppl 1):S Rosenstock J, et al. Diabetes Obes Metab. 2015;17:

5 Strategies to Intensify Insulin Therapy Sequentially add prandial insulin doses Switch to premixed insulin Provides basal and prandial insulin in a single injection in a fixed-dose ratio Switch to full basal-bolus dosing Involves multiple daily injections of insulin Shaefer CF, Anderson J. Postgrad Med. 2016;128: SC Insulin Administration Correction dosing is pre-emptive vs SSI which is a reaction to existing hyperglycemia Scheduled (SSI only uses this component) Correction Basal Bolus (Nutritional) Correction Total daily insulin needs Basal Nutritional Long-acting insulin Rapid-acting insulin SSI, sliding scale insulin Clement S et al. Diabetes Care. 2004;27: Moghissi ES et al; American Association of Clinical Endocrinologists; American Diabetes Association. Endocr Pract. 2009;15(4):

6 Sliding-Scale Insulin Definition Use of a mealtime insulin, typically regular insulin, as the sole insulin for managing a patient s diabetes i.e., no scheduled basal or prandial insulin Potential problems Poor control of hyperglycemia (does not address basal insulin needs); also does not address pre meal needs Insulin stacking Hypoglycemia Not preferred method of SC insulin delivery American Diabetes Association. Diabetes Care. 2014;37(suppl 1):S14 S80. Browning LA, Dumo P. Am J Health Syst Pharm. 2004;61(15): Hirsch IB. JAMA. 2009;301(2): Strategies to Intensify Insulin Therapy Patients who have severe insulin resistance (e.g., require >200 U of insulin) may benefit from receiving concentrated insulin formulations High doses of less concentrated insulin may cause variability in insulin absorption because of volume problems High insulin dosages may require multiple injections Shaefer CF, Anderson J. Postgrad Med. 2016;128:

7 U-500* Insulin in Clinical Practice: % of Patients Achieving HbA1c level <7%, 7.5%, and 8% Percentage of patients Before U-500 After 6 months of U-500 HbA1c <7% HbA1c <7.5% HbA1c <8% Last visit *Now available in a pen Boldo A, Comi RJ. Endocr Pract. 2012;18(1): Converting U-100 Insulin Dosing to U-500 Insulin Dosing If the total daily insulin dose is <200 U First divide by 5 Then split to twice-daily dosing 60% of the total daily dose given before the morning meal 40% given before the evening meal A total of 180 U per day; 180 U 5=36 U, the patient can take 22 U before breakfast and 14 U before dinner. If the total daily dose is >200 U First divide by 5 Then use 3x-daily dosing (at breakfast, lunch, and bedtime) 40% of the total daily dose given before the morning meal 30% at each of the next 2 meals A total of 360 U per day; 360 5=72 U, the patient can take 28 U before breakfast and 22 U before lunch and before dinner 14 7

8 Glargine U-300 Dosing in T2DM Insulin naïve patients Changing patients already on a once daily long-acting or intermediate acting insulin Patients controlled on insulin glargine, 100 units/ml Changing patients from twicedaily NPH Dose adjustments/titration 0.2 units per kilogram of body weight once daily The dosage of other anti-diabetic drugs may need to be adjusted when starting to minimize the risk of hypoglycemia Start U-300 at the same dose as once daily long-acting dose Higher daily dose of U-300 will probably be needed to maintain the same level of glycemic control Recommended starting U-300 dose is 80% of the total daily NPH dosage The recommended days between dose increases is 3-4 days Monitor glucose frequently in the first weeks of therapy; titrate the dose of U-300 per instructions and the dose of other glucoselowering therapies per standard of care 1. Toujeo [package insert]. sanofi-aventis; Degludec Dosing in T2DM Insulin naïve patients Patients already on insulin therapy Dose adjustments/titration 10 units SC daily Start insulin degludec at the same unit dose as the total daily long- or intermediate-acting insulin unit dose The recommended days between dose increases is 3-4 days Individualize dose based on type of diabetes, metabolic needs, blood glucose monitoring results and glycemic control 1. Tresiba [package insert]. Novo Nordisk;

9 Inhaled Insulin in T2DM Results at week 24 in a RCT of adults (N=353) with T2DM inadequately controlled on oral antidiabetic drugs (OADs) Reduction in HbA1c (%) % patients achieving HbA1c 7% Inhaled insulin + OADs (n=177) % Placebo + OADs (n=176) % Afrezza (Insulin Human) Inhalation Powder [package insert]; MannKind Corp:

Intensifying Insulin Therapy

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