Subcutaneous Insulin in Hospitalized Patients

1. Subcutaneous Insulin in Hospitalized Patients Cheryl W. O’Malley, MD Cheryl.Omalley@bannerhealth.com

2. Welcome Glycemic Control “Experts”

3. Prepare yourself for the questions… • “Why do we need to worry about glycemic control, hasn’t that been proven to harm patients?” • “Can’t we just use their home regimens?” • “We have become pretty good with sliding scale, I’d prefer to just use that?” • “I really don’t know how to dose insulin for someone who is ‘naïve’, can you help?” • “I don’t want to use these expensive regimens because non of our patients can afford them when they go home”

4. Why is this important despite recent controversies • Affects a large number of patients • Robust physiologic and observational data that some sort of control matters • Current consensus with the ADA/AACE is to target moderate control • Traditionally we have used sliding scale which doesn’t work • Safety issues related to insulin

5. Current Recommended Glycemic Control Targets for ICU= 140-180 mg/dL NICE Sugar 118 <40 70 100 130 140 160 180 200 250 299 400 2009 AACE/ADA goals

6. “For the majority of noncritically ill patients treated with insulin, the premeal BG target should generally be <140 mg/dl in conjunction with random BG <180 mg/dl. • Modify regimen if < 100 mg/dL to minimize risk of hypoglycemia • DIABETES CARE, VOLUME 32, NUMBER 6, JUNE 2009

7. Why can’t we just use their home meds?

8. Oral Agents in the Hospital Sulfonylureas Hypoglycemia (long acting) Metformin Lactic acidosis risk =renal insufficiency, hypotension, CHF GI (nausea, abd. pain, diarrhea) Thiazoladinediones (TZDs) or “glitazones” Possible liver toxicity Fluid overload, CHF Inability to titrate (very slow onset of action) Only pioglitazone approved for use with insulin

9. “I get pretty good control with sliding scale…”

10. Does this look familiar?

11. Case: Sliding Scale Only “non-fasting blood sugar upon admission was 560, the patient had a redraw at 6:05 and it was 369. Diabetes mellitus type 2, uncontrolled. Once the patient's blood sugar is better controlled, will change Accu-Checks to q.a.c and q.h.s. and cover with Apidra sliding scale insulin and Lantus if necessary”

12. Sliding Scale Alone Doesn’t Work Sliding scale prospective cohort study 171 patients with type 1 DM 40% had BG>300 23% <70 In 80% of patients, the orders written at admission were never changed despite poor control Quele et al, Arch Intern Med 1997: 157; 545-552

13. A look at “the real world”: Mayo Scottsdale Retrospective Analysis 2,916 discharges Teaching hospital (200 bed; metro. Phoenix) LOS 3 or more days; non-ICU Mean 1st 24 hours 170  stay 167 mg/dL last 24 h 165 mg/dL Highest tertile (mean 218 mg/dL) 46% still only on sliding scale regular insulin only 60% increased insulin doses Cook CB, et al. J Hosp Med. 2007.

14. Scheduled subcutaneous administration of insulin, with basal, nutritional, and correction components, is the preferred method for achieving and maintaining glucose control.” • DIABETES CARE, VOLUME 32, NUMBER 6, JUNE 2009

15. Physiologic Insulin Secretion Normal 24-Hour Profile 1. Nutritional Insulin: Promote glucose utilization 50 Insulin (µU/mL) 25 2. Basal Insulin: Suppresses Glucose Production Between Meals And Overnight 0 Breakfast Lunch Supper 150 100 Glucose (mg/dL) 50 3. Correction/ Supplemental Insulin: Additional insulin to treat hyperglycemia 0 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 A.M. P.M. Time of Day

16. Human Insulins and AnalogsTypical Times of Action

17. Pharmacokinetics of Insulin Preparations Short acting Analog Regular NPH Glargine Detemir Insulin Effect 8 AM 8 AM N 6 PM 10 PM 6-23

18. Using Exogenous Insulin to Imitate Physiologic Insulin Secretion: Summary • Basal insulin: Use non-peaking, longer-acting insulins • Glargine or detemir are preferred • NPH also possible • Nutritional insulin: Depends on the type of nutrition • Rapid-acting insulin is preferred when patients are eating meals • Regular insulin also possible • Correctional insulin: Use rapid-acting (or regular) insulin • Usually the same as the nutritional insulin

20. RABBIT-2 Trial: Basal / Bolus arm • D/C oral antidiabetic drugs on admission • Starting total daily dose (TDD): • 0.4 U/kg/d x BG between 140-200 mg/dL • 0.5 U/kg/d x BG between 201-400 mg/dL • TDD adjusted daily +/- 20% for BG >140 or < 70 • Half of TDD as insulin glargine and half as rapid-acting insulin (lispro, aspart, glulisine) • Insulin glargine - once daily, at the same time/day. • Rapid-acting insulin- three equally divided doses (AC) Smiley & Umpierrez, Southern Med J, June 2006

21. Mean Blood Glucose Levels During Insulin Therapy * * * ¶ ¶ ¶ ¶ * p<0.01 ¶ p<0.05 Day 3: P=0.06 Umpierrez, Diabetes Care 30: 2007

22. Blood Glucose Levels in Patients Who Failed SSRI: Transition to Basal Bolus Insulin P: 0.02 P: NS ¶ ¶ ¶ ¶ ¶ Failure was defined as 3 consecutive BG values > 240 mg/dL during SSRI Umpierrez, Diabetes Care 30: 2007

23. 130 nonsurgical non-critically ill patients age 18-80 with known type 2 diabetes admitted to noncritical care unit Half of patients were receiving insulin prior to admission and received similar outpatient insulin dose in the hospital Randomly assigned to: Detemir once a day with premeal Aspart 3 times a day NPH and regular twice a day before breakfast and dinner Dosing 0.4 units per kg/day for BG 140-200 0.5 units per kg /day for BG > 200 Distribution of insulin Determir group: 50% given as detemir and 50% as aspart NPH group: 2/3 given as NPH and 1/3 as regular DEAN Trial Detemir with Aspart vs NPH with Regular Insulin Therapy in the Inpatient Management of Patients With Type 2 Diabetes Umpierrez et al. J Clin Endocrinol Metab. 94:564 2009

24. DEAN-Trial Detemir + Novolog NPH + Regular Blood glucose (mg/dL) Duration of Therapy (days) Data are ± SEM Basal/bolus regimen: Detemir was given once daily and Novolog before meals. NPH/regular regimen: NPH and Regular insulin were given twice daily, 2/3 A.M., 1/3 P.M.

25. Percent of Glucose Values Within Target (<140 mg/dl) RABBIT-2 Trial DEAN Trial * 66% 48% 45% % % 38% * P < 0.01 Umpierrez et al. Diabetes Care 30:2181–86, 2007 Umpierrez et al. JCEM, in press

26. Rate of Hypoglycemia (# patients with BG < 60 mg/dl) RABBIT-2 Trial DEAN Trial 32.8 25.4 % % 3 3 Umpierrez et al. Diabetes Care 30:2181–86, 2007 Umpierrez et al. JCEM, in press

27. DEAN Trial Discussion • 50% of patients were on insulin prior to admission • Detimir may need to be dosed bid • NPH/R and detimir/aspart were equivalent in this study. • Choice depends on physician preference, formulary choice, cost, and nursing considerations.

28. So, how can I figure out my patient’s doses?

29. 3 Steps to using basal/bolus insulin in the hospital • Determine total daily insulin dose • Divide up to 50% basal insulin, 50% bolus • Adjust daily

30. Step 1: Calculate Starting total daily dose (TDD): • IV requirements • Home dose—be careful of “I use basal + sliding scale”…how many units of all types of insulin do they use on any given day • Weight based 0.2-0.6 units/kg/day • AACE slides said 0.2-0.4 • What we do at BGSMC • 0.3 ESRD or • 0.4 units/kg/day lean (BMI <25) • 0.5 units/kg/day overweight (BMI 25-30) • 0.6 units/kg/day obese (BMI >30)

31. But at home they eat poorly and here we are giving them a diabetic diet…

32. Physiologic Insulin Requirementsin Health and Illness Relative proportion of insulin Clement, Braithwaite, Magee et al. Diabetes Care. 2004;27:553-591.

33. How often do patients become NPO or have poor po intake when hospitalized?

34. Step 2: Divide into Scheduled Basal vs. Nutritional Insulin • 40-50% should generally be basal (glargine, detimir, or NPH) • Remaining 50-60% divided evenly and given to cover nutritional intake • Rapid acting (lispro, aspart, glulisine) easier to match with meals in hospital • Regular insulin also an option

35. Case: Hypoglycemia Why? Home regimen: Glargine 120 qhs, 60 q am Byetta—held at admit Glimipiride—held at admit Glargine 120 Glargine 100 Glargine 60 units

36. Total Daily Dose of Insulin Divided to Match Needs • 50% “Bolus” • Rapid Acting • Lispro • Aspart • Glulisine • Short Acting • Regular 0 • 50% “Basal” • Glargine • Detimir • NPH

37. Basal insulin only when NPO 100% Basal

38. Continuing Nutritional Insulin when NPO 50% Basal 50% Bolus

39. Split mixed insulin when NPO 70% Basal 30% Bolus

40. Problems if you discontinue all scheduled insulin • Sliding scale only • DKA • Severe uncontrolled hyperglycemia

41. The “Sweet” balance in NPO Patients 50% Basal

43. Step 3: Adjust Doses Daily • If some BG were <100 mg/dL • Reduce TDD by 20-50% • Re-divide the new TDDI to preserve the desired ratio • If some were over 180 mg/dL and none less than 100 then • Add up ALL of the insulin given in the last 24 hours this was the real TDDI • Add 10% to the TDDI from the prior day • Re-divide the new TDDI to preserve the desired ratio

44. “Insanity: Doing the same thing over and over again and expecting different results” – Albert Einstein

46. Case 3: Daily Adjustments • 47 y.o. HF with DM type 2 X 13 years • Admitted for Pyelonephritis • HbA1c 9.4% & admission BG 370 • Home regimen metformin 500 mg bid Glargine 35 units glulisine 12 with meals Glargine 64 units glulisine 20 with meals

47. Management of Hyperglycemia is a safety concern with risks due to • Numerous insulin types with varying onset/peak and poor staff understanding. • Changes in food/CHO intake • Change in clinical status or medications • Failure to adjust daily based on BG patterns • Prolonged use of SSI as monotherapy • Poor coordination of BG testing with insulin administration and meal delivery • Poor communication during patient transfers • Errors in order writing and transcription

48. RISKS Numerous insulin types Changes in food/CHO intake Poor coordination of BG testing with insulin administration and meal delivery Errors in order writing and transcription SOLUTIONS: Order sets Teams Limiting insulin options on order sets Include provisions for change in po intake Management of Hyperglycemia is a safety concern with risks due to

49. 3 (+1) Steps to Using Basal/Bolus Insulin in the Hospital Determine total daily insulin dose Divide up to 50% basal insulin, 50% bolus Reassess daily USE YOUR HOSPITAL ORDER SETS

50. Effect of Structured Insulin Orders and an Insulin Management Algorithm – UCSD RR Uncontrolled Patient-Day 0.77 (0.74 - 0.80) RR Uncontrolled Patient-Stay (70% controlled vs. 60%) 0.73 (0.66 - 0.81) RR Hypoglycemic Patient-Day (prevents 208 / year) 0.68 (0.59 - 0.80) RR Hypoglycemic Patient-Stay 0.77 (0.64 - 0.92) 5,530 patients with DM or Hyperglycemia and > 7 POC Glucose readings TP3:TP1 Maynard G, et al. J Hosp Med. 2009.