Starting and Managing Patients On Insulin Therapy

Starting and Managing Patients On Insulin Therapy December 10, 2011 Rahim Hirji, MD, MSc, CCFP Marilyn McInnes, RN, BA, MEd, Inge Schabort, MB, ChB, CCFP 1

Disclosure Marilyn McInnes:Eli Lilly National Advisory Board 2

Outline Presentation objectives Effects of insulin Mechanism of action Route of administration Classification of types of insulin Initiating insulin therapy Adjusting insulin therapy 3

Primary Objectives Demystify insulin therapy Add tools to your toolbox Provide a practical primary care approach to initiating and adjusting insulin therapy 4

Why is a Discussion about Insulin Important? Mainstay treatment for all type I and many type 2 DM patients Many Family Physicians (and residents!) are apprehensive about initiating and adjusting insulin DM clinic not readily available in all communities Initiating and adjusting insulin can be confusing! 5

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8 Stewart Harris, 2006

Type 2 DM: -Cell Failure is Progressive 100 75 -Cell function (%) 50 25 9 9 0-12 -10-6 -2 0 2 6 10 14 Diagnosis Years from diagnosis Dashed line shows extrapolation forward and backward from years 0 to 6 based on HOMA data from UKPDS. Lebovitz H. Diabetes Rev 1999;7:139 153. Holman RR. Diabetes Res Clin Pract 1998;40(suppl):S21-S25.

10 Stewart Harris, 2006

Type I DM Approximately 10% of all DM patients Characterized by destruction of pancreatic beta cells Usually autoimmune Leads to absolute insulin deficiency Develop DKA if not given insulin Intensive insulin therapy (MDI) recommended 11 11

Type 2 DM Most common type of DM Characterized by variable degrees of insulin deficiency and resistance 12 12

Insulin Potent primary hormone responsible for controlling uptake, utilization and storage of cellular nutrients Stimulates anabolic actions: Intracellular utilization and storage of glucose, amino acids and fatty acids Glycogen synthesis Inhibits catabolic processes e.g. glycogenolysis 13 13

Time-Activity Profile Post-prandial insulin secretion in normal subjects generally biphasic Phase 1 Rapid rise in insulin secretion after meal Peak after 1-2 minutes Phase 2 Delayed onset and longer duration 14

Insulin Sources Recombinant DNA technology Chemically identical to human insulin Insulin analogs by modifying the AA sequence of insulin molecule 15 15

Insulin Injection Sites Sites abdomen, thighs, arms abdomen- best absorption (avoid 2 inches around the navel) If using NPH insulin Hs: use buttocks or thighs - less risk of nocturnal hypoglycemia Rotate sites weekly overuse of sites causes lipohypertrophy and affects absorption inspect injection sites for lipohypertrophy Site rotation Incidence of lipohypertrophy Same site always used 86% Rotation each injection 77% Rotation weekly 21% 17 16 (TITAN). Frid A, Hirsch L et al. Diabetes and Metabolism, 2010,36 (supp 2):S19-29)

Needle Size All patients can safely use 4 mm needle as skin thickness not > than 2.4mm Include pinching up of skin fold if using longer than 6mm needle (or 5mm in lean patients) to avoid muscle injection of insulin 18 17 (Frid A., Hirsch et al Diabetes and Metabolism, 2010,36 (sup 2):S19-29)

Storage of insulin Novolin insulins are stable for 30 days and Humulin insulins are stable for 28 days at room temperature Both brands are stable for 3 months once open if refridgerated Exceptions: Glargine: 28 days (even if refridgerated) Levemir: 42 days Never leave in the car or freeze/extreme temperatures could render insulin ineffective Insulin not in use should be refridgerated good unopened until expiry date 18 18

Insulin Types and Action Rapid Humalog, Novo-rapid, Apidra Short Humulin Regular Novolin Toronto Intermediate Humulin N Novolin NPH 19 19 Long : Lantus Levemir

Normal Pancreatic Function *Basal: Beta cells secrete small amounts of insulin throughout the day # Bolus: At mealtime, insulin is rapidly released in response to food #Bolus Insulin Meal Meal Meal *Basal Insulin 20 Expected insulin changes during the day for individuals with a healthy pancreas *Insulin effect images are theoretical representations and are not derived from clinical trial data.

Case #1 Mr. M 60 y.o. male, type 2 x14 yrs. wt = 90 Kg No drug coverage Hx NSTEMI Meds: Metformin 2g/day Glyburide 20mg/day FBS 9-11 mmol/l CBS range 9-16 mmol/l A1c 0.092 Symptomatic Patient not willing to add more oral agents Day FBS PC BF AC lunch PC lunch AC dinner PC dinner Mn 9.0 11.3 12.1 Tu 12 11.6 We 9.6 11.3 16.0 Th 11 11.4 12.1 13 HS 21

Refresher on the Targets Blood glucose: Fasting: 4-7 2hr.pc: 5-10 but consider 5-8 if AIC target not met A1C:.07 Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2008 Clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes. 2008;32(suppl 1):S1-S201. 22

Achieve Target A1C within 6 12 Months Clinical assessment and Lifestyle intervention (nutrition and activity) A1C < 9% A1C 9% If not at target, add... metformin Acarbose DPP-4 inhibitor Insulin Secretagogue TZD Weight loss agent -Initiate Insulin or metformin with another agent from a different class immediately without waiting for effect from lifestyle changes -Symptomatic hyperglycemia, with metabolic decompensation: Initiate insulin ±metformin 23 Timely adjustments/additions should be made to attain target A1C within 6 12 months. Adapted from: Canadian Diabetes Association Clinical Practice Guidelines. Can J Diabetes 2008;32(Suppl 1):S56.

Indications for Insulin in Type 2 Initial therapy in cases of marked hyperglycemia Defined as A1C 9.0% (CPG, 2008) If glycemic targets not reached with oral agents If oral agents are contraindicated e.g. hepatic/renal disease When metabolic decompensation occurs At any time!! 24 Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2008 Clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes. 2008;32(suppl 1):S1-S201. 24

Goals of Insulin Therapy Improve glycemic control Reduce risk of developing microvascular and macrovascular complications Improve health and well-being 25 25

Advantages of Insulin No maximum or minimum dose- easy to titrate No contraindications Only two side effects Weight gain, hypoglycemia Providing insulin replaces a deficiency An old drug, proven safe & effective No serious drug interactions 26 26

Why is Insulin not Used Early? More psychology than medicine art and science to insulin therapy Regular provider threats to use the needle Messaging use of insulin = I failed diabetes Marketing Provider anxiety/time constraints r.e. starting insulin Fear of pain, weight gain, hypoglycemia I am doomed mother took insulin and died soon after 27 27

Is there Evidence for Early Insulin vs. Pushing Oral Agents? INSIGHT Trial In people with Type 2 DM who o Are treated with LSM alone, 1 agent or sub-maximal doses of 2 OHA by specialists or generalists, AND o Can easily be managed without insulin, Does the addition and titration of glargine to the above mentioned regimens improve glycemic control? Results o 1.7x more likely to achieve HbA1c 6.5% (20% vs. 12%) and 7% (50% vs. 30%) o no difference in hypoglycemia rates 28 28

Percentage decrease in relative risk corresponding to a 1% decrease in HbA1C Decreased Rel. Risk of Diabetes-related Complications Associated with a 1% Decrease in A1c Observational analysis from UKPDS study data Any diabetesrelated endpoint Diabetesrelated death All cause mortality Myocardial infarction Stroke Peripheral vascular disease Microvascular disease Cataract extraction 21% 14% 21% ** 14% ** 12% * 19% ** ** ** Lower extremity amputation 43% or fatal peripheral vascular disease 37% ** 29 29 *P = 0.035; **P < 0.0001 **

Action Profiles of Insulins Lispro/Aspart/Apidra 4 6 hours BOLUS INSULINS Regular 6-10 hours NPH 12 20 hours BASAL INSULINS Levemir ~ 6-23 hours Lantus~ 10-26 hours 30 30 Hours Note: action curves are approximations for illustrative purposes. Actual patient response will vary. Mayfield, JA.. et al, Amer. Fam. Phys.; Aug. 2004, 70(3): 491 Plank, J. et.al. Diabetes Care, May 2005; 28(5): 1107-12

HS Insulin N/ NPH, Lantus (glargine), or Levemir (detemir) Can be added HS without discontinuing oral agents Caution if on Thiazolidinedione (TZD) e.g. Actos, Avandia o o May cause edema/chf Canadian recommendation is to stop TZD when start insulin Suppresses nocturnal hepatic glycogenolysis - prevents fasting hyperglycemia Less weight gain with HS insulin, especially in combination with metformin Rosenstock et al a Randomized 52 week treat to target trial comparing insulin detemir with insulin glargine when administered as add on to glucose lowering drugs in insulin naïve people with type 2 diabetes.diabetologia 2008,51:408-16 Riddle,M.,Rosenstock,J.Gerich,J., Treat to Target Trial Diabetes Care 26.3080-86 2003 American Diabetes Association 31 31

NPH vs. Lantus and Levemir Newer long acting clear insulins Cannot be mixed in same syringe with any insulin Onset 90 minutes, no peak, lasts up to 24 hours Studies comparing NPH, Levemir and Lantus in type 2 both equal for euglycemia 50-87% increase in hypoglycemia with NPH 32 32 Philis-Tsimikas A, Charpentier G, Clauson P, Ravn GM, Roberts VL, Thorsteinsson B. Clin Ther. 2006 Oct;28(10):1569-81.Comparison of once-daily insulin detemir with NPH insulin added to a regimen of oral antidiabetic drugs in poorly controlled type 2 diabetes. Fonesca, V., Bell, D., Berger, S., Thomson, S., Mecca, T. (2004). A comparison of bedtime insulin glargine with NPH in patients with type 2 diabetes a subgroup analysis of patients taking once daily insulin in a multicenter randomized parallel group study. American Journal of Medical Sciences, 328(5), 274-279.

Capillary Blood Glucose Monitoring (CBGM) CDA 2010 stands by its 2008 recommendations : Recommended for all individuals with diabetes; Individualize to the person with diabetes; Must be part of a holistic education program; Should be reassessed at frequent intervals. 33

Are the Tests Accurate? Accuracy of monitor depends on the user Check fasting venous vs CBG: 20% variation (CPG 2008) Are recorded test results:upside down, real /fiction Correct technique, strips, date, code, clean hands All meters have a memory 34 34

Patient s Can Err Elderly patient stated had 2 lows since MD increased Actos dose 1 week ago Log book : L.9 1.9 Actual reading: 6.7 6.1 ( pt. read monitor upside down) 35 35

Patients Can be Creative Patient s Logbook date am Lunch supper hs 23 8.1 7.8 7.6 7.7 24 7.2 7.4 7.9 7.8 25 7.4 7.9 7.8 7.4 26 7.8 7.6 8 7.9 27 7.8 7.9 7.2 8 Monitor s Memory date am lunch supper Hs 23 12.1 24 7.2 25 9 10 26 7.8 27 14.1 36

How Often to Test? Once daily not enough Can test QID one day, BID on the next day Type 2 patients can test q 2-3 days at least BID Encourage inclusion of 2 hrs pc test (A1c = 60%pc) Important to observe patterns of blood sugars best way to adjust medication appropriately 37 37

Increasing Contribution of PPG as A1c Improves FPG PPG 30% 70% 50% 50% 55% 45% 60% 40% 70% 30% < 7.3 7.3 to 8.4 8.5 to 9.2 9.3 to 10.2 > 10.2 A1C Range (%) 38 38 (American Diabetes Association Diabetes Care 24(4), 2001: 775-778) Adapted from Monnier L, et al. Diabetes Care. 2003;26:881-885

Suggested Testing Schedule date B after B L after Lunch s after Sup. bed comments 12 x x x 13 x x 14 x x x 15 x x x x 39

Case #1 Mr. M 60 y.o. male, type 2 x14 yrs, wt =90 Kg No drug coverage Hx NSTEMI Meds: Metformin 2g/day Glyburide 20mg/day FBS 9-11 mmol/l CBS range 9-16 mmol/l A1c 0.092 Symptomatic Patient not willing to add more oral agents WHAT NEXT? 40 Day FBS PC BF AC lunch PC lunch AC dinner PC dinner Mon 9.0 11.3 12.1 Tues 12 11.6 Wed 9.6 11.3 16.0 Thurs 11 11.4 12.1 13 HS

How to Initiate HS Insulin Reinforce lifestyle modifications Ensure capillary tests are accurate 41 41

Case #1 cont d How to Initiate HS Insulin Continue oral agents and add: 5-10 units of glargine or levemir qhs if patient obese 3-5 units of glargine or levemir qhs if patient thin Add 2-4 units q 4 th night until FBS @ target patient can self adjust if competent 42 42

Adjusting Insulin Adjust to decrease hypoglycemia risk first Base changes on patterns of glucose tests taken at different times over a few days e.g. patterns of food, exercise, and CBS Never react to a single test i.e. fasting venous (a moment in time) or just A1C J. Rosenstock & M. Davies & P. D. Home & J. Larsen &C. Koenen & G. SchernthanerDiabetologia (2008) 51:408 416DOI 10.1007/s00125-007-0911- xa randomised, 52-week, treat-to-target trial comparinginsulin detemir with insulin glargine when administeredas add-on to glucose-lowering drugs in insulin-naive people with type 2 diabetes 43 43

Case #1 Cont d Mr. M. started on 8 units NPH Hs minimal improvement in CBG Day FBS PC BF AC lunch PC lunch AC dinner PC dinner qhs NPH titrated up by 4 units q 4days for 2 weeks Pt on 24 units NPH Significant improvement in CBG Feeling much better! Mon 6.8 8.7 7.7 Tues 7.6 9.1 Wed 6.1 8.1 9.5 Thurs 6.5 7.4 7.9 7.8 44

Case #2 Mr. P 52 y.o. male, type 2 DM x 8 yrs Meds: 12 units NPH Hs Metformin 1000 BID Diamicron MR 120 mg q a.m. FBS 6.1-6.8 mmol/l PC meals 9.9-12.3 mmol/l qhs 11.6-13.0 mmol/l Pt refuses more than 2 injections per day o SUGGESTIONS? Day FBS PC BF AC lunch PC lunch AC dinner PC dinner qhs Mon 6.8 9.9 13.0 Tues 11.1 11.8 Wed 6.1 9.6 10.8 Thur 6.5 10.8 10.1 11.1 45

Control Poor with qhs NPH? Can continue metformin Discontinue insulin secretagogues (e.g. glyburide, gluconorm, diamicron) To avoid hypoglycemia Commence BID insulin 46 46

Initiating BID Insulin Start with the following units of NPH per kg body weight: 0.1-0.2 (thin) 0.2-0.3 (normal weight) 0.3-0.5 (obese) Give 2/3 total daily dose in am & 1/3 HS 47 47

Case #2 Cont d Consider insulin BID d/c insulin secretagogue (diamicron MR) Continue metformin Patient wt = 80 Kg (BMI 31) Insulin start NPH 0.3 units / Kg = 24 units o 2/3 of insulin in a.m. (16 units) o 1/3 HS (8 units) 48

Case #2 Cont d Recall Mr. P s insulin regimen was: NPH 16 units qam, 8 units qhs Moderate improvement in CBG Dose increased by patient every 4 th day patient made one change at a time Day FBS PC BF AC lunch PC lunch AC dinner PC dinner qhs Mon 6.8 8.7 7.7 Patient now on NPH 34 units qam, 16 units qhs Significant improvement in CBG Feeling much better! Tues 7.6 9.1 Wed 6.1 8.1 9.5 Thurs 6.5 7.4 7.9 7.8 49

Case # 3 Mrs. T 45 yr old female on: - Humalog Mix 25 20 units qam - Humalog 10 units ac supper - Humulin N 20 units qhs Day FBS PC BF AC lunch PC lunch AC dinner PC dinner Q Hs CBS range 6-13 CBS range ac/pc lunch 8.5-13 mmol/l Mon 6.1 7.1 9.8 Tues 8.5 12 Wed 6.3 8.9 10.1 WHAT NEXT? Thur s 6.8 7.8 12.8 8.1 11 50

Insulin Types and Action Insulin Type Content Onset Peak Lasts (hrs) PRE MIX (Humalog Mix 25) 25 % Humalog 0.1-0.4 1-12 18-24 75 % NPL Rapid (Humalog) Intermediate (Humulin N) Humalog 0.1-0.4 1-2.5 3-5 hrs Humulin N 1-3 4-12 18-24 51

Switching to MDI MDI = Multiple Daily Injections of insulin 4 injections per day 2 (or more) types of insulin Superior glycemic control with MDI* *2008 CDA Clinical Practice Guidelines Expert committee 52 52

concentration profile (mu/l) Basal-bolus Therapy Attempts to Create Physiological Insulin Secretion re- Predicted plasma insulin Rapid-acting insulin Basal insulin Total Time of day 53 Adapted from: 1.Leahy JL. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker, Inc.; 2002. 2. Bolli GB, et al. Diabetologia. 1999;42:1151 1167.

Switching to MDI Cont d Switching to MDI with N/NPH: 40% of intermediate acting (N/NPH) insulin qhs 60% of insulin during meals o o Rapid or fast acting insulin (novo-rapid, apidra, humalog) Distribute based on meal size or patient can carb count Switching to MDI with Levemir or Lantus: 50% of long acting (Levemir/Lantus) o qhs, or at same time everyday 50% of rapid-acting insulin with meals o o Rapid or fast acting insulin (novo-rapid, apidra, humalog) Distribute based on meal size or patient can carb count *2008 CDA Clinical Practice Guidelines Expert committee. Rosenstock & M. Davies & P. D. Home & J. Larsen & C. Koenen & G. Schernthaner Diabetologia (2008) 51:408 416DOI 10.1007/s00125-007-0911-xA randomised, 52-week, treat-to-target trial comparing insulin detemir with insulin glargine when administered as add-on to glucose-lowering drugs in insulin-naive people with type 2 diabetes 54

Switching to MDI 55 Case # 3 Cont d Patient s insulin regimen (50 units total): Humalog Mix 25: 20 units q am Humalog 10 units ac supper Humulin N 20 units q.hs, Mealtime insulin 50 units x 60% = 30 units of Lispro (Humalog) o o o 8 units with breakfast 10 units with lunch 12 units with dinner Bedtime insulin 50 units x 40% = 20 units of NPH Note: would be 50/50% mealtime/bedtime if switching to Levemir or Lantus (instead of NPH) as bedtime insulin

Case #3 Cont d Mrs. T s insulin regimen was switched to: Lispro 8 units with breakfast Lispro 10 units with lunch Lispro 12 units with dinner NPH 20 units at bedtime Day FBS PC BF AC lunch PC lunch AC dinner PC dinner qhs Moderate improvement in CBG Dose increased by patient every 4 th day patient made one change at a time Patient now on Lispro 12 units with breakfast, 12 units with lunch, 14 units with dinner, and NPH 28 units at bedtime Significant improvement in CBG Feeling much better! 56 Mon 6.8 8.7 7.7 Tues 7.6 9.1 Wed 6.1 8.1 9.5 Thurs 6.5 7.4 7.9 7.8

Table of Suggestions for Insulin Adjustment LOW HIGH HIGH consider GLUCOSE DECREASE ( If not Somogyi) INCREASE adding: FASTING Hs insulin Hs insulin rapid or fast acting at supper Before LUNCH rapid or shortacting at breakfast rapid or shortacting at breakfast increase breakfast % of R or Toronto in pre mix i.e. 30/70 to 40/60 or change to novo mix 30 or humalog premix Before SUPPER breakfast intermediate or long-acting, or lunch rapid or short-acting breakfast intermediate or long-acting, or lunchtime rapid or short-acting fast or rapid acting at lunch or intermediate at breakfast bedtime supper short or rapid-acting supper short or rapid-acting supper short or rapidacting 2. hrs pc meal time rapid meal time rapid 57 Reference: McInnes M, Wheeler,M.. Managing Type 2 Diabetes (an evidence-based tool), Sept/04.

Case # 4 Mrs. S 54 y.o. female, type 2 DM x 2 years Insulin regimen: -40 units Novolin 30/70 ac breakfast 20 units Novolin 30/70 ac supper qhs BS 4.5-7 mmol/l, but fasting BS 9-18 mmol/l over past week WHAT NEXT? Day FBS PC BF AC lunch PC lunch AC dinner PC dinner qhs Mon 9.0 9.4 10 5.7 Tues 10.3 8.1 8.8 5.2 Wed 12.0 6 4.5 Thurs 18 58

Pre-mixed Insulin Type Content Onset Novolin 30/70 30% Toronto 70% NPH (hrs) Peak Lasts 0.5 2-12 18-24 59

Case # 4 Cont d Increases 30/70 at supper to 22 units x 3 days no improvement in a.m. fasting CBS Increases to 24 units ac supper x 3 days Again, no improvement in a.m. fasting CBS ANY THOUGHTS? 60 60

Somogyi Phenomenon Rebound hyperglycemia from hypoglycemia Thought to involve counter-regulatory hormones, which stimulate gluconeogenesis and glycogenolysis Nocturnal hypoglycemia can be caused by: o o too much bedtime insulin 30/70 or NPH insulin at supper Yale,J.,Begg,I.,Gerstein,H.C.,Houlden, R., Jones, H., Maheuz,P., Pacaud, D. 2001 Canadian Diabetes Assoc. Clinical practice Guidelines for the Prevention and Management of Hypoglycemia in diabetes. Canadian Journal of Diabetes /26:1 61 61

Symptoms of Somogyi in Night Nightmares Waking up with wet pillow from sweating Waking up with headache Restless sleep High fasting blood sugar 62 62

Diagnosis of Somogyi Have patient test at 0300 hrs 2 nights in a row Or treat as somogyi if severe hypoglycemia suspected 63 63

Somogyi Treatment Option # 1 Change to BID premixed analogue Novo Mix 30 or Humalog Mix 25 but decrease supper Dose by 10-20 % 40 units Novo Mix 30 q am; 18 unit s Novo Mix 30 at supper 64 64

Somogyi Treatment Option #2 Break up 30/70 supper dose 20 units 30/70= 30% Toronto /R = 20 x 30%= 6 units T 70% N/ NPH = 20 X 70% =14 units N o o o Give 30% rapid-acting at supper (6 units) Give NPH qhs BUT decrease dose to 10 units Decrease am dose from 40 units to 36 units (10%) as NPH will overlap am insulin 65 65

2008 Recommendations for Treating Hypoglycemia Mild <4 : oral ingestion of 15 grams of glucose preferably glucose or sucrose tablets Severe:< 2.8 in a conscious person use 20 grams RETEST blood glucose in 15 minutes and re treat with 15 grams if <4 Follow with ingestion of starch and protein or next meal Patients must not drive until at least 45 minutes after effectively treating hypoglycemia. In unconscious home patient use glucagon adult 1mg, child 0.5 mg *2008 CDA Clinical Practice Guidelines Expert committee Yale,J.,Begg,I.,Gerstein,H.C.,Houlden, R.,Jones, H., Maheuz,P., Pacaud,D. 2001 Canadian Diabetes Assoc. Clinical practice Guidelines for the Prevention and Management of Hypoglycemia in diabetes. Canadian Journal of Diabetes /26:1 CDA CPG s for diabetes and private and Commercial driving Canadian Journal of diabetes 2003:27(2) 128-140 66 66

Case # 5 Mr. S Male age 45, type 2 x 4 yrs :Works 12 hr. shifts at Dofasco on metformin Meals irregular, often skipped Current insulin regimen: Humulin N 15 units 6 am & 6 pm. but often forgets 2 nd injection at 6pm and takes it at midnight Day FBS PC BF AC lunch PC lunch AC dinner PC dinner qhs Mon 5.1 7.1 19.1 Tues 5.3 6.2 Humalog 10-15 units each meal CBS s vary from 3-18 SUGGESTIONS? Wed 7.2 12.3 14.2 Thurs 3.8 8.9 14.1 17.7 67 67

Types of Insulin Action Name Starts (hours) Peaks (hours) Lasts (hours) Rapid Humalog 0.1-0.4 1-2.5 3-5 Intermediate Humulin N 1-3 4-12 18-24 68

Case # 5 The Issues Risk for nocturnal hypoglycemia with Humulin N given at 6pm Humulin N could peak at same time as Humalog when given irregularly Potential risk if patient working night shifts Inconsistent timing increases risk of hypoglycemia & hyperglycemia Missing insulin changes basal amount SUGGESTIONS? 69 69

Case # 5 Cont d Change basal insulin to Lantus or levemir & give HS or at same time everyday If using Lantus decrease by 20% at first N 15 & 15 =30 units - 20%=24 units of Lantus qhs If using levemir dose is same as NPH i.e.30 units of levemir qhs Can continue Humalog or change to apidra at each meal Consider carb counting to guide insulin dose Adjust by 5-10% every 4 th day until at target 70 70

Types of Insulin Action Name Starts (hours) Peaks (hours) Lasts (hours) Rapid Lispro (Humalog) 0.1-0.4 1-2.5 3-5 Long Glargine (Lantus) Detemir (Levemir) 1.5 None 10-24 71

Case #5 Cont d Recall Mr. S s insulin regimen was: Humulin N 15 units 6am and 6pm (irregular use) Humalog 10-15 units with each meal Insulin regimen changed to: Glargine 24 units at bedtime Humalog 10-15 units with each meal Day FBS PC BF AC lunch PC lunch AC dinner PC dinner qhs Moderate improvement in CBG Dose increased by patient every 4 th day patient made one change at a time Patient now on glargine 32 units at bedtime, Humalog 10-15 units with each meal Significant improvement in CBG Feeling much better! 72 Mon 6.8 8.7 7.7 Tues 7.6 9.1 Wed 6.1 8.1 9.5 Thurs 6.5 7.4 7.9 7.8

Case # 6: Mrs. Chemo Mrs.Chemo: 54 yrs old, wt=100kg Type 2 X 10 years Medications: glyburide10 mg BID metformin 1000 mg BID CBS: were all 6-8, A1C 6.7 Started chemotherapy : Decadron 4mg q am Day FBS PC BF AC lunch PC lunch AC dinner PC dinner qhs CBS s after treatment initiated: fasting: 8, Lunch: 20, supper: 25, Hs: 16 Mon 7.8 9.4 16 Tues 19.5 23.1 Wed 8.2 24.3 27 Thurs 8.0 21.0 25 15.5 73 73

Case # 6 The Issues Steroids cause insulin resistance and increased catecholamines Result = hyperglycemia Effect decreased as steroid action wanes often overnight Glucose levels often low fasting higher at noon and supper lower Hs Need to address rising glucose in the day Glyburide not maintaining euglycemia SUGGESTIONS? 74 74

Case # 6: Cont d Stop glyburide Continue metformin Initiate insulin @ 0.3 units/kg 30/70 10 units in am Short (Toronto / R) or rapid (Lispro / Aspart) o o 10 units at lunch 10 units at supper No insulin Hs (yet) morning glucose lowest Note: when change steroid dose, reassess CBS May be able to switch back to oral hypoglycemics 75 75

Adjusting for Exercise & Activity Can increase carbohydrate consumption Can decrease insulin in anticipation of increased activity 10% for light exercise 20% for moderate 30-40% for vigorous Should monitor CBS to determine if successful in achieving balance between food/exercise/insulin Note: Hypoglycemia can occur up to 24-30 hours after exercise 76 76

Adjusting for Special Occasions Extra rapid or short-acting insulin before Or after within 15 minutes of the meal 1 unit of rapid acting insulin per 15 grams of extra carbohydrate 77 77

78 78 Summary of Key Numbers qhs insulin Keep all orals (except TZD s) 5-10 units starting dose Titrate by 2-4 units q 4days BID insulin N/NPH Stop all orals except metformin Starting dose based on weight o 2/3 of Total Daily dose (TDD) qam, 1/3 TDD qhs Titrate by 2-4 units q 4days MDI insulin Stop all orals except metformin Using N/NPH and rapid o o N/NPH: 40% TDD qhs Rapid: 60%TDD divided over meals Using Lantus/Levimir and Rapid o o Lantus /Levimir: 50% TDD qhs Rapid 50%TDD divided over meals Titrate by 2-4 units q4 days

Conclusion You CAN initiate and adjust insulin therapy in the primary care setting!! 79 79

References 1.Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2008 Clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes. 2008;32(suppl 1):S1-S201. 2. CPS. Compendium of Pharmaceuticals and Specialities (2010).Canadian Pharmacists Assoc. 3. Rosenstock et al a Randomized 52 week treat to target trial comparing insulin detemir with insulin glargine when administered as add on to glucose lowering drugs in insulin people with type diabetes.diabetologia 2008,51:408-16 naïve 4 (TITAN) Frid A, Hirsch L et al. Diabetes and Metabolism, 2010,36 (supp 2):S19-29) 5. Davidson,J., Anderson,J. jr.,chance,r.(2000) Insulin Therapy.Clinical diabetes, a problem oriented approach, 329-403. 6.Cheng, A.Y.,& Zinman,B.(2001).Insulin for treating type 1 and type 2 diabetes. Gerstein,H.c.,& Haynes,B., (Eds.) Evidence-based diabetes care.bc Decker Inc., Hamilton, Ont. 322-349. 7. Herbst, K., Hirsch, I.(2002). Insulin Strategies for Primary care providers. Clinical Diabetes 20:11-17. 8. Yki-Jarvinen, H.(2001).Combination therapies with insulin in type 2 diabetes.diabetes Care 24:758-767. 9. Nathan, D.M., Diabetologia 2006; 49:1711 10. Mcinnes,M.,(2001) Insulin Adjustment for pharmacists. Living healthy with diabetes: part 2 CD Rom.Katz Phamacy Services 11. Aventis, Pharma Inc. (2005). Lantus insulin glargine product monograph. Aventis Pharma Inc. Laval, Quebec. 12. Philis-Tsimikas A, Charpentier G, Clauson P, Ravn GM, Roberts VL, Thorsteinsson B. Clin Ther. 2006 Oct;28(10):1569-81.Comparison of once-daily insulin detemir with NPH insulin added to a regimen of oral antidiabetic drugs in poorly controlled type 2 diabetes. 13. Fonesca, V., Bell, D., Berger, S., Thomson, S., Mecca, T. (2004). A comparison of bedtime insulin glargine with NPH in patients with type 2 diabetes a subgroup analysis of patients taking once daily insulin in a multicenter randomized parallel group study. American Journal of Medical Sciences, 328(5), 274-279.5. 14 Hirsch, I. (2005). Insulin analogues. The New England Journal of Medicine, 352 (2), 174-183. 15. Lam, S. (2003). Insulin glargine a new once daily basal insulin for the management of type 1 and type 2 diabetes mellitus. Heart Disease, 5 (3), 231-240. 16.Hirsch IB, Bergenstal RM, Parkin CG, et al. A real-world approach to insulin therapy in primary care practice. Clinical Diabetes 2005;23:78-86. 17.ldiko Lingvay, et al Insulin-Based versus Triple Oral Therapy for Newly-Diagnosed Type 2 Diabetes: Which is Better? Diabetes Care ; July 10, 2009, 18. Insulin Intensification info@mdpp.mdpassport.com2011 19.Leahy JL. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker, Inc.; 2002. 20.Bolli GB, et al. Diabetologia. 1999;42:1151 1167. 80 80

81 Thank you.

Questions r.hirji@utoronto.ca pmcinnes4@bell.net ischabo@mcmaster.ca 82 82

Sample Prescriptions Humulin N insulin units qhs ( or as directed) 3ml penfills Humalog units TID ac (or as directed) 3 ml penfills needles for pen (4mm) 100 Lancets, 100 strips for glucometer. 3 months supply 83 83

Sample Prescription: Lantus Lantus Solostar pen ClikSTAR pen and 3 ml lantus cartridges Needles for pen 4mm Take as directed (or specific instructions) or Lantus 10 ml vial Insulin syringes: 100 units /1 ml size 84 84

Sample Prescription: Novolin Novolin Levemir 3 ml penfills Novo rapid 3 ml penfills Needles for pen 4mm OR Novolin NPH,(or novo rapid) 10 ml vial Syringes 1 ml, 0.5 ml, 0.3 ml 85 85

Diabetes Websites www.diabetes.ca http://care.diabetesjournals.org www.diabetesclinic.ca www.diabetes.org www.diabetesmonitor.com www.diabeticgourmet.ca 86 86