Mixed Insulins Pick Me

Transcription

1 Mixed Insulins Pick Me Alvin Goo, PharmD Clinical Associate Professor University of Washington School of Pharmacy and Department of Family Medicine Objectives Critically evaluate the evidence comparing the efficacy and safety of mixed versus basal analogs. Discuss advantages and disadvantages of mixed versus basal analogs. Apply your knowledge and assist providers with adjusting mixed insulin. 1

2 Case The provider requests your recommendation regarding which insulin to initiate. 37 yo male with increasing symptoms of hyperglycemia. Recent A1c 10.8% Metformin ER 500mg 2tabs twice daily Glipizide 10mg twice daily Indapamide 2.5mg daily Gather information Information and risk for hypoglycemia Complete medication list (OTC, supplements) Renal function Neuropathy Current glycemic control Hx of Cardiovascular disease Meals / Nutrition Daily routine, work Vision Dexterity 2

3 Basal Analogs Mixed insulins Case How about starting glargine (basal analog)? Daily, easier for the patient to self administer Efficacious Safer; less hypoglycemia, peak less therefore safer 3

4 Basal analogs versus mixed insulin Efficacy Ease of administration Safety (risk for hypoglycemia) A) Degludec B) Detemir C) Glargine D) Mixed insulin E) NPH Insulin parameters Onset Peak effect Duration of action NPH 1 2hrs 4 10hrs 14 20hrs NPH 70/ min 2 12hrs Up to 20hrs Mixed analogs 10 30min 1 4hrs Up to 20hrs Glargine 1 3hrs Flat, Max in 5hrs 18 26hrs Insulin Detemir 1 3hrs Max in 5hrs 18 26hr Insulin Degludec 1 3hrs No Peak >24hrs Degludec / Aspart 70/ mins ½ 2hrs >24hrs 4

5 Glargine versus Degludec Haahr H, Heise T. Clin Pharmacokinet 2014;53(9):787 Degludec Haahr H, Heise T. Clin Pharmacokinet 2014;53(9):787 Risk of hypoglycemia NPH Basal Analogs A) < 10% A) < 10% B) 11 20% B) 11 20% C) 21 40% C) 21 40% D) 41 50% D) 41 50% E) > 50% E) > 50% 5

6 Lantus Package Insert Lantus n=357 NPH n=389 Severe 9 (2.5%) 7 (1.8%) NS Hypoglycemia Nocturnal 94 (25.6%) 136 (35%) Symptoms Weight (Kg) NS Severe symptomatic hypoglycemia was defined as an event with symptoms consistent with hypoglycemia requiring the assistance of another person and associated with either a blood glucose below 50 mg/dl Nocturnal symptomatic hypoglycemia as defined as symptoms which occurred while the patient was asleep between bedtime and before getting up in the morning p Newer Lantus package insert Severe hypoglycemia type 2 diabetes 52 weeks Oral combination 28 weeks with regular insulin 5years with regular insulin Lanutus NPH Lantus NPH Lantus NPH Rate 1.7% (5/289) 1.1% (3/281) 0.4% (1/259) 2.3% (6/259) 7.8% (40/513) 11.9% (60/504) Rates of hypoglycemia Glargine versus NPH studies Study Name Types of Hypoglycemia Rates of Hypoglycemia by type Eliaschewitz (24 weeks) Symptomatic Nocturnal symptomatic Confirmed nocturnal symptoms Severe symptomatic Fritsche (24 weeks) All episodes All episodes of symptomatic Nocturnal Severe Rosenstock (28 weeks) Symptomatic Nocturnal Severe Hsia (24 weeks) Symptomatic Nocturnal Fasting Severe Glargine QHS NPH QHS p value 52.8 % 20.4 % 16.9 % 2.6 % QHS 68 % 43 % 23 % 1.8 % QAM 74 % 56 % 17 % 2.1 % 61.3% 31.3 % 0.04 % (n=1) QHS 6.7 % 0.2 % 1.8 % 0 QAM 9.6 % 0.3 % 3.2 % % 34.8 % 30.0 % 4.4 % QHS 75 % 58 % 38 % 2.6 % 66.8 %* 40.2 % 2.3 % (n=6) QHS 8.2 % 0.3 % 4.2 % <0.001 < > <0.001 > >0.05 NS >0.05 NS >0.05 NS 6

7 Glargine vs Mixed insulin GALAPAGOS study Glargine n=258 Glargine w Glulisine n=197 Mixed QD n=159 Mixed BID n=287 HbA1c <7% 57.6% 24.4% 55.7% 50.9% Insulin Dose U/kg Overall Hypoglycemia Events / Pt Year 22.6% % % % 3.4 Nocturnal Events / Pt Year 7.9% % % % 1 Aschner P, et al. J Diab Comp 2015;29(6):838 Mixed lispro versus glargine and detemir for type 2 diabetes Trials wks Overall hypoglycemia rates were not significantly different Esposito K, et al. Diabetes Care 2012;35(12):2698 7

8 Esposito K, et al. Diabetes Care 2012;35(12):2698 Esposito K, et al. Diabetes Care 2012;35(12):2698 Degludec / Aspart vs Mixed Aspart Administered before breakfast and evening meal for 26 weeks Degludec w Aspart n=197 Mixed Aspart n=188 Weight +1.7kg +2.2kg Insulin dose 1.8units/kg 1.2units/kg Mean dose 38am 52pm 44am 54pm Fulcher GR, et al. Diabetes Care 2015:37(8):2084 8

9 32% lower rate with Deg/Asp CI vs 14 episodes Per Pt Year 73% lower rate with Deg/Asp CI vs 2.5 episodes Per Pt Year Switching from Basal Bolus to Mixed Aspart Dieuzedie G, et al. Primary care diabetes 2014;8(2):111 9

10 Switching from Basal Bolus to Mixed Aspart Glargine + Bolus NPH + Bolus Baseline 24wks P Baseline 24 wks P Hypoglycemia 5% 1.5% < % 3.4% <0.001 Major 0.2% 0% P< % 0% <0.001 Nocturnal 0.9% 0% P< % 0.8% <0.001 Mean Wtkg Dieuzedie G, et al. Primary care diabetes 2014;8(2):111 Rising prices of insulin Eli Lilly, Novo Nordisk, Sanofi Drug price Humulin R U % Epipen 223% Levemir 169% Lantus 168% /diabetes drugs compete with prices that rise in lockstep Similar prices 10

11 Good Rx Lantus $387 Levemir $417 Tresiba $552 Tuojeo $349 Humalog $506 Novolog $502 Humulin N $449 Novolin 70/30 $147 Humulin 70/30 $446 Novolog 70/30 $502 Humalog 75/25 $505 Advantages and disadvantages Basal Mixed insulins Initial daily dosing Initial daily dosing Cost with adding preprandial insulin 3 4 injections with adding preprandial Take prior to meals Stacking with 3 injections/day Basal Analogs 11

12 Case 37 yo male with increasing symptoms of hyperglycemia. Recent A1c 10.8% Metformin ER 500mg 2tabs twice daily Glipizide 5mg twice daily Indapamide 2.5mg daily Discuss your choice of insulin What is your recommendation? Basal analog NPH Mixed insulin NPH 70/30 Mixed analog Mixed insulin adjustments Glycemic control remains suboptimal AM s Bedtime 250 s AM s Before dinner 250 s AM 200 s Before dinner 150 s 12

13 Case 56 yo female with type 2 diabetes Metformin 1000mg twice daily Glargine 70 units twice daily Home glucose 300 s Discuss your plan regarding insulin adjustments Insulin initiation Assess for risk factors for hypoglycemia Assist patient with lifestyle goals and activities Injection sites / techinque Proper insulin storage / re suspension Recommendation Basal insulin: 10 15units daily increase gradually NPH Bedtime, Dinner, Morning NPH 70/30 before Dinner or largest meal Mixed analog before breakfast and dinner (might require 3 rd dose at noon) Consider Basal analogs Nocturnal / Morning hypoglycemia with NPH Pt requires assistance with insulin injections Seeking to de prescribe 13