INSULIN 101: When, How and What
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1 INSULIN 101: When, How and What Alice YY
2 Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied, stored, or transmitted in any form or by any means graphic, electronic, or mechanical, including photocopying, recording, or information storage and retrieval systems without prior written permission of Sea Courses Inc. except where permitted by law. Sea Courses is not responsible for any speaker or participant s statements, materials, acts or omissions.
3 Faculty/Presenter Disclosure Alice Cheng Relationships with commercial interests: Grants/Research Support/Clinical Trials: Amgen, Sanofi, Eli Lilly, Pfizer, Novo Nordisk Speakers Honoraria: Abbott, AZ, BD, BI, BMS, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi, Valeant Consulting Fees: Abbott, AZ, BI, BMS, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi, Servier, Valeant Other:
4 Learning objectives By the end of this session, you will be able to: 1.Recognize when to initiate insulin 2.Discuss the 3 insulin types and regimens 3.Understand how to dose and titrate insulin
5 When should insulin be started in type 2 diabetes?
6 1. Max non-insulin agents but A1c > 7% 2. New diagnosis > 8.5% 3. Metabolic decompensation 4. End-organ failure 5. Pre and during pregnancy 6. Acute illness / Drugs 7. Whenever you feel like it!
7 Insulin All options open COULD THE PATIENT BE INSULIN DEFICIENT? Lower BMI Lack of glycemic lowering with other meds Duration of T2DM (sometimes) Higher BMI Shorter duration of T2DM (sometimes) Consider the core defect! Insulin is REPLACEMENT therapy
8 Why don t we use more?
9 How to choose type and regimen? The Rule of 3 s
10 3 Types of insulins BOLUS Regular (R or Toronto) Aspart (Novorapid) Glulisine (Apidra) Lispro (Humalog) Lispro 200 u/ml (Humalog) Faster aspart (Fiasp) BASAL NPH Detemir (Levemir) Glargine 100 u/ml (Lantus) SEB glargine 100 u/ml (Basaglar) Degludec (Tresiba) Glargine 300 u/ml(toujeo) PRE-MIXED 30/70 Insulin lispro/lispro protamine (Humalog Mix25, Mix50) Biphasic insulin aspart (Novomix 30)
11
12 3 Types of insulins BOLUS Regular (R or Toronto) Aspart (Novorapid) Glulisine (Apidra) Lispro (Humalog) Lispro 200 u/ml (Humalog) Faster aspart (Fiasp) BASAL NPH Detemir (Levemir) Glargine 100 u/ml (Lantus) SEB glargine 100 u/ml (Basaglar) Degludec (Tresiba) Glargine 300 u/ml(toujeo) PRE-MIXED 30/70 Insulin lispro/lispro protamine (Humalog Mix25, Mix50) Biphasic insulin aspart (Novomix 30)
13 Relative Glycemic Effect Time-action profile of basal insulins NPH Detemir Glargine Duration in Hours McMahon GT, Dluhy RG. NEJM 2007;357:1759.
14 Basal insulin therapy: The next generation Gla-300 degludec Gla-300, insulin glargine 300 U/mL; IDeg, insulin degludec
15 Glargine 300 U/mL: Next Generation 1/3 volume, flatter and longer PK/PD Reduction of volume by 2/3 100 U/mL (U100) 300 U/mL (U300) Reduction of depot surface by 1/2 100 U/mL (U100) 300 U/mL (U300) Glucose infusion rate, mg/kg/min Euglycemic clamp study in patients with T1D after 8 days treatment Time, h U U/kg U U/kg Blood glucose, mmol/l Becker RHA et al. Diabetes Care. 2014; Published ahead of print: doi: /dc PD, pharmacodynamic; PK, pharmacokinetic
16 Participants, % Gla-300: Percentage of participants (T2DM) reporting 1 hypoglycemic event at any time (24 hours) Participants with 1 confirmed ( 3.9 mmol/l) and/or severe hypoglycemia, % 100 Relative risk 0.91 (95% CI 0.87, 0.96) Gla-300 (n = 1242) Gla-100 (n = 1246) Relative risk 0.83 (95% CI 0.77, 0.89) Relative risk 0.92 (95% CI 0.86, 0.98) Entire treatment period (Baseline to Month 6) Titration period (Baseline to Week 8) Maintenance period (Week 9 to Month 6) Significant Clinical Implications From pooled T2D population across entire treatment period: For every 15 subjects initiated and treated with Gla-300 instead of Gla-100, 1 less patient will have confirmed hypoglycemia at any time (24 hours) Ritzel R, et al. Diab Obes Metab 2015; 17:
17 Glucose Infusion Rate in T1DM patients at Day 6, mg/kg/min Insulin Degludec: Next Generation Flatter and longer PK/PD Upon subcutaneous injection forms soluble and stable multihexamers, that allow slow and continuous absorption of monomers into the circulation 1,2 A half-life of ~25 hours, and is detectable in serum for >120 hours post-injection U/kg 0.6 U/kg 0.4 U/kg Hours 1. Owens DR, et al. Diabetes Metab Res Rev. 2014;30: Shah VN, et al. Diabetes Technol & Ther. 2013;15: Heise T, et al. Diabetes Obes Metab 2012;14:944 50
18 Estimated RR reduction IDeg: Overall hypoglycemia rates vs. Gla-100 Meta-analysis of Phase IIIa trials in overall T2DM population OVERALL confirmed (BG <3.1 mmol/l) or severe hypoglycemia Entire treatment period Titration period Maintenance period (Baseline to 26 or 52 weeks) (Baseline to 15 weeks) (16 weeks onwards) RR: 0.92 ( ) RR: 0.83 * ( ) RR: 0.75 * ( ) Clinical Implications *Significant RR, rate ratio From pooled overall T2DM population across entire treatment period: For every 3 subjects initiated and treated with degludec instead of Gla-100 for 1 year, 1 overall confirmed episode will be avoided Ratner RE, et al. Diab Obes Metab. 2013;15:175 84
19 3 Types of insulins BOLUS Regular (R or Toronto) Aspart (Novorapid) Glulisine (Apidra) Lispro (Humalog) Lispro 200 u/ml (Humalog) Faster aspart (Fiasp) BASAL NPH Detemir (Levemir) Glargine 100 u/ml (Lantus) SEB glargine 100 u/ml (Basaglar) Degludec (Tresiba) Glargine 300 u/ml(toujeo) PRE-MIXED 30/70 Insulin lispro/lispro protamine (Humalog Mix25, Mix50) Biphasic insulin aspart (Novomix 30)
20 Relative Glycemic Effect Aspart Glulisine Lispro Human Regular Duration in Hours McMahon GT, Dluhy RG. NEJM 2007;357:1759.
21 Faster acting insulin aspart: Earlier onset of appearance and greater early pharmacokinetic and pharmacodynamic effects than insulin aspart Diabetes, Obesity and Metabolism Volume 17, Issue 7, pages , 8 MAY 2015 DOI: /dom
22 3 Types of insulins BOLUS Regular (R or Toronto) Aspart (Novorapid) Glulisine (Apidra) Lispro (Humalog) Lispro 200 u/ml (Humalog) Faster aspart (Fiasp) BASAL NPH Detemir (Levemir) Glargine 100 u/ml (Lantus) SEB glargine 100 u/ml (Basaglar) Degludec (Tresiba) Glargine 300 u/ml(toujeo) PRE-MIXED 30/70 Insulin lispro/lispro protamine (Humalog Mix25, Mix50) Biphasic insulin aspart (Novomix 30)
23 Insulin effect Premixed Humalog Mix25, Mix50 Novomix 30 Humulin or Novolin 30/70 Premixed analogue Premixed human B L Time of administration D HS
24 3 Insulin Regimens
25 Insulin effect Normal Insulin Secretion: The Basal-Bolus Insulin Concept Endogenous Insulin Bolus Insulin Basal Insulin B L Time of administration D HS B = breakfast; L = lunch; D = dinner; HS = bedtime. 1. Leahy JL. In: Leahy JL, Cefalu WT (eds). Insulin Therapy. Marcel Dekker Inc., New York, Bolli GB, et al. Diabetologia 1999; 42:
26 Insulin effect Basal insulin Endogenous Insulin Bolus Insulin Basal Insulin B L Time of administration D HS B = breakfast; L = lunch; D = dinner; HS = bedtime. 1. Leahy JL. In: Leahy JL, Cefalu WT (eds). Insulin Therapy. Marcel Dekker Inc., New York, Bolli GB, et al. Diabetologia 1999; 42:
27 Basal insulin affects Breakfast Lunch Supper Before After Before After Before After Bedtime Sunday Monday Tuesday Wednesday Thursday
28 Type 2 Diabetes Insulin Options Basal (continue all oral agents) NPH at bedtime Glargine once daily at any time of the day Detemir once daily at any time of the day Pros and cons Basal Plus or Basal-Bolus Meal-time insulin added at largest meal (or breakfast) Multiple daily injections (meal-time + basal) Premixed (continue metformin) Premixed at one or more meals
29 Insulin effect Basal Plus Bolus (main meal) Endogenous Insulin Bolus Insulin Basal Insulin B L Time of administration D HS
30 Basal-plus will affect Breakfast Lunch Supper Before After Before After Before After Bedtime Sunday Monday Tuesday Wednesday Thursday
31 Insulin effect Basal-Bolus Insulin Endogenous Insulin Bolus Insulin Basal Insulin B L Time of administration D HS B = breakfast; L = lunch; D = dinner; HS = bedtime. 1. Leahy JL. In: Leahy JL, Cefalu WT (eds). Insulin Therapy. Marcel Dekker Inc., New York, Bolli GB, et al. Diabetologia 1999; 42:
32 Basal-bolus will affect Breakfast Lunch Supper Before After Before After Before After Bedtime Sunday Monday Tuesday Wednesday Thursday
33 Type 2 Diabetes Insulin Options Basal (continue all oral agents) NPH at bedtime Glargine once daily at any time of the day Detemir once daily at any time of the day Basal Plus or Basal-Bolus (cont met) Meal-time insulin added at largest meal (or breakfast) Multiple daily injections (meal-time + basal) Pros and cons Premixed (continue metformin) Premixed at one or more meals
34 Insulin effect BID Premixed Endogenous Insulin B L D HS Time of administration
35 If on premixed Breakfast Lunch Supper Before After Before After Before After Bedtime Sunday Monday Tuesday Wednesday Thursday Reflects the bolus portion of the premixed injection at breakfast / dinner
36 If on premixed Breakfast Lunch Supper Before After Before After Before After Bedtime Sunday Monday Tuesday Wednesday Thursday Reflects the intermediate portion of the premixed injected the night before / breakfast
37 Type 2 Diabetes Insulin Options Basal (continue all oral agents) NPH at bedtime Glargine once daily at any time of the day Detemir once daily at any time of the day Basal Plus or Basal-Bolus Meal-time insulin added at largest meal (or breakfast) Multiple daily injections (meal-time + basal) Premixed (continue metformin) Premixed at one or more meals Pros and cons
38 How do the regimens compare? Basal start has advantages (4T) Diabetes is PROGRESSIVE The regimen must change over time All roads lead to Basal Bolus concept If you re not going to TITRATE don t start
39 Intensification of Therapy in T2DM A1C above target FBG above target A1C above target FBG at target A1C above target Basal Plus Add bolus insulin at main meal Basal Add basal insulin and titrate Basal bolus Additional prandial doses as needed OHA monotherapy and combinations Lifestyle changes OHA=oral hypoglycaemic agent Progressive deterioration of -cell function Adapted from Raccah D. et al. Diabetes/Met Res & Rev 2007;23:
40 Intensification of Therapy in T2DM A1C above target FBG above target A1C above target FBG at target A1C above target Basal Plus Add bolus insulin at main meal Basal Add basal insulin and titrate Basal bolus Additional bolus doses as needed OHA monotherapy and combinations Lifestyle changes OHA=oral hypoglycaemic agent Progressive deterioration of -cell function Adapted from Raccah D. et al. Diabetes/Met Res & Rev 2007;23:
41 How to dose? Whatever you pick will be WRONG and that s okay!
42 Basal insulin self-titration tool You will inject units of insulin each night You will continue to increase by 1 unit every night until your blood sugar level is mmol/l before breakfast Do not increase your insulin when your fasting blood sugar is 4-7 mmol/l
43 Basal Plus or Basal-bolus If full Basal-Bolus: 0.5 u/kg = TDI 50% bolus, 50% basal (or 60:40) OR Add 10% of basal dose as bolus insulin ac meal (4T-study) OR Add 2 units of bolus insulin at a meal and self-titrate (START protocol) OR Add 4 units of bolus insulin at a meal and self-titrate (STEPwise protocols)
44 Premixed 0.5 units / kg = TDI 1/2 in the AM + 1/2 in the PM OR 5-10 units BID
45 What about the orals? METFORMIN METFORMIN Secretagogues if basal alone TZD stop DPP-4 benefit but cost GLP-1 receptor agonist benefit (dose & weight) but cost SGLT2 inhibitor benefit but cost
46 How can I remember??
47 CHOOSE AN INSULIN TYPE CHOOSE A BRAND DOSING SEE REVERSE FOR TIPS SELECT PEN DEVICE CHECK OFF SUPPLIES QUANTITY & REPEATS SIGN AND DATE
48 guidelines.diabetes.ca/bloodglucoselowering/insulin PrescriptionTool
49 Summary 3 types of insulin 3 generations of insulin 3 types of regimens Pick a starting dose it will be wrong just be sure to titrate Change over
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