Insulin Initiation and Titration

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Insulin topics we will not cover today Inhaled Insulin Insulin Pump Insulin management of the surgical and ICU patient Insulin Requirements in Pregnancy

Goals for this session: Know the indications for starting insulin Know typical starting dose of Daily intermediate or long-acting insulin Titrate the intermediate or long-acting insulin based on glucose readings Be able to calculate starting doses based on weight for 70/30 insulin BID dosing Titrate the 70/30 insulin based on glucose readings Identify causes of hypoglycemia and hyperglycemia Manage hypoglycemia and hyperglycemia

Complete 3 activities after this lecture Calculating Insulin Starting Doses and Titration Case Studies How to draw up and inject insulin Hypoglycemia & Hyperglycemia identification & treatment. Glucose monitoring and the importance of the glucose logbook in titrating insulin doses.

Insulin types

Insulin Terms Basal Insulin Replacement That insulin required to suppress hepatic glucose production overnight and between meals

Basal Insulin Action Product When to Take Onset Peak Duration Intermediate NPH (neutral protamine hagedorn) BID 1-4 hours 4-12 hours 14-26 hours NPL* (neutral protamine lispro) 1-2 hours 6 hours 15 hours Long Glargine (Lantus) Determir (Levermir) Usually bedtime** Glargine No peak; determir 3-9 hours Up to 24 hours Ultra-long Degludec (Tresiba) Once daily No peak Up to 42 hours *In the US NPL is only available in combination with lispro (ie: Humalog mix) **Long acting insulin may be given at any time of day because theoretically it does not peak. However, it must be given at the same time each day. Long acting insulin is usually given once a day, but may be given twice a day in rare instances. NPH is usually given twice a day (except when adding to oral hypoglycemic medications – it is given once daily at bedtime).

Insulin Terms Bolus (prandial or mealtime) insulin replacement That insulin required to utilize glucose after eating Correction dose (also called supplement) Additional insulin for pre-meal hyperglycemia Can also be between-meal hyperglycemia This insulin can only be regular, lispro, aspart, or glulsine

Bolus & Correction Insulin Action Product When to Take Onset Peak Duration Rapid Lispro (Humalog) Aspart (NovoLog) Glulisine (Apidra) 0-15 minutes before a meal 10-30 minutes 30 minutes - 3 hours 3-5 hours Short Regular (R) Human 30 minutes before a meal 30 minutes 1-5 hours 8 hours With the exception of marked hyperglycemia (correction dose) do NOT administer bolus insulin (rapid or short acting) without the patient eating afterwards or hypoglycemia will occur.

Pre-mixed Humulin 70/30 Humalog Mix 75/25 Humulin 30/30 Rapid Acting with Intermediate (NPL + Rapid) Short Acting with Intermediate (NPH + Regular) Humulin 70/30 Humulin 30/30 Novolin 70/30 Humalog Mix 75/25 Humalog Mix 50/50 Novolog Mix 70/30

What is the shelf-life of insulin after it is opened? 28 days 7-14 DAYS

Care of Insulin Intermediate-acting insulins that are not refrigerated should be kept as cool as possible [<86°F], but not frozen. Insulin glargine, once opened, should be stored in a refrigerator or kept as cool as possible. Advise patients that all insulins need to be stored out of direct sunlight and kept from extremes of temperature.

When should you start insulin? Type I Diabetes Always

When should you start insulin in Type II Diabetes? Glucose levels are so acutely elevated that immediate safety is a concern Marked hyperglycemia OR Significant weight loss OR Severe/significant symptoms OR 2+ or greater ketonuria OR DKA/ hyperosmolar state OR Severe intercurrent illness or surgery Chronic suboptimal control of glucose despite oral hypoglycemic medications/GLP-1 agonists/ Fasting Plasma Glucose > 140 OR 2 Hr Postprandial Plasma Glucose > 180 OR A1C > 7.0%

What fears do patients have about starting insulin?

Insulin Initiation Options for Type II Patients It should be noted that there is great clinician variation when it comes to administering types and scheduling of insulin. The most important is to get the patient at goal without causing hypoglycemia.

Insulin options for patients with Type II DM 1) Continue PO medications & add nighttime basal insulin 2) Pre-mixed Insulin Program 3) Basal insulin + mealtime (bolus) insulin We will not cover this today

Option #1: Continue PO medications & add nighttime basal insulin NOTE: This is NOT an option for patients with Type II DM who have an A1c >8.5% on max oral hypoglycemics (they will never get to goal). This is NOT an option for Type I diabetics

PO medications + Basal Insulin Initiation Continue oral agents Add single dose nighttime basal insulin (intermediate {NPH} or long acting insulin {glargine or determir}) Begin with a single dose of 10 Units at bedtime (or 0.2 Units/kg)….start with lower doses in elderly patients, severe CKD….

PO medications + Basal Insulin Titration Check and log daily morning (fasting) blood glucose Keep increasing the night time basal insulin by 2 units every 3 days until morning (fasting) blood glucose is consistently less than 130 If hypoglycemia occurs or AM blood glucose is <70 on any one reading, Decrease nighttime basal insulin by 4 units.

EXAMPLE A 84 kg male has consistent elevated glucose readings, and A1C of 7.8 on Metformin 1g BID, Glyburide 10mg BID, and Pioglitazone 30mg daily. The patient has normal estimated CrCl. Plan: Nighttime basal insulin: glargine or determir or NPH is added to the patient’s medications

EXAMPLE Q: The patient was started on 10 Units of nighttime glargine in addition to his PO medications: glyburide 5mg BID, Metformin, 1g BID, and Pioglitazone 30mg daily. He checks his fasting glucose every morning and calls you with the following AM results from the past 4 days: 180, 160, 173. What should be done next? A:

EXAMPLE Q: The patient calls you in 4 days with the following AM fasting readings: 136, 128, 134, What should you tell the patient? A:

EXAMPLE Q: The patient calls you in 4 days with the following AM fasting readings: 102, 98, 88. What should you tell the patient? A:

Option #2: Pre-mixed Insulin Program 70/30 or 75/25 or 50/50 insulin

Premixed Insulin Program Taper and discontinue oral antihyperglycemic medications as insulin is initiated and adjusted, particularly if using short or rapid-acting + basal insulins (exception is METFORMIN - Type 2 diabetics on insulin can improve their glycemic control and lower their insulin dose with metformin.) There is an increased risk for edema when insulin and a thiazolidinedione are used together. Rosiglitazone should not be used in combination with insulin. I personally continue metformin (if the patient has no contraindications to this medication) and discontinue all other diabetic medications if I am switching entirely to insulin. Because you shouldn’t be giving a sulfonyurea with short-acting insulin & TZDs (ie rosiglitazone) may increase edema if given with all that insulin.

Pre-mixed Insulin Initiation Calculate Total Daily Insulin Requirement = 0.5Units/Kg (consider lower if the patient is very active, elderly, has chronic kidney disease, or is taking Metformin) 70/3o insulin: give 2/3 QAM (before breakfast) and 1/3 QPM (before dinner) *** Do NOT administer pre-mixed insulin without eating afterwards – hypoglycemia will occur. Short acting intermediate – give 30 minutes before breakfast and dinner Rapid acting intermediate – give right before breakfast and dinner. “give the shot while the meal is hot” Note: if a patient was started on insulin in the hospital via sliding scale – you may use the total amount of required insulin/day for the total daily insulin * Give 2/3 insulin dose before breakfast as this will cover breakfast and lunch. 1/3 will cover dinner Benefit – easy dosing, easy to administer (twice a day), easy to titrate based on twice a day glucose readings. Better control than once daily basal insulin. Disadvantage – the patient has to eat consistent meals 3 times a day (and may require a bedtime snack). This regimen may not give as accurate control (as the last option that requires more # of shots a day).

PRACTICE Calculate your own total starting dose of 70/30 insulin based on your weight in Kg. Now divide total into 2/3 in the AM (pre-breakfast) and 1/3 in the PM (pre-dinner)

Example Q: Calculate the insulin for a patient starting 70/30 insulin who is 200 lbs A:

Example Q: Calculate the insulin for a patient starting 70/30 insulin who is 140 lbs (64 kg) A:

70/30 Insulin Titration Check glucose & log readings at least twice a day – pre breakfast and pre dinner (or with any signs of hyper or hypoglycemia) *Important – pre breakfast glucose reading reflects the amount of insulin given pre dinner. Pre dinner glucose reading reflects the amount of insulin given pre breakfast.

70/30 Insulin Titration Monitor and log readings for 3 days: If pre breakfast glucose is >130 INCREASE pre dinner insulin by 2 units If pre dinner glucose is >130 INCREASE pre breakfast insulin by 2 units If pre breakfast glucose is >200 INCREASE pre dinner insulin by 4 units If pre dinner glucose is >200 INCREASE pre breakfast insulin by 4 units * If unexplained hypoglycemia (any reading <70), decrease the insulin by 4 units. (example – pre dinner glucose is 68 that is not explained by any change in eating/activity – decrease the pre-breakfast insulin by 4 units)

EXAMPLE – 70/30 insulin Your patient is taking 70/30 insulin 20 Units before breakfast and 12 Units before dinner returns with the following glucose readings Pre breakfast 20U Pre dinner 12 Units 300 220 253 215 Plan?

EXAMPLE – 70/30 insulin For the next 2 days, the glucose readings on 24 units QAM & 16 units QPM are: Pre breakfast Pre dinner 102 167 118 140 Plan?

EXAMPLE – 70/30 insulin Now the patient has the following readings on 26 Units QAM and 16 Units QPM Pre breakfast Pre dinner 60 (skipped dinner the night before) 220 116 210 Plan? * High AM glucose readings in a patient taking NPH insulin may be due to the Somogyi effect. Having the patient randomly taking the glucose @ 2am will diagnose this phenomenon: if glucose is low @ 2am – decrease the pre dinner insulin (because of the Somogyi effect); if it is high (dawn phenomenon), then increase the pre dinner insulin

EXAMPLE 70/30 insulin titration Now the patient has the following readings on 30 Units QAM and 16 Units QPM Pre breakfast Pre dinner 92 115 127 132 Plan?

Option #3: Basal insulin + mealtime (bolus) insulin For Type II patients who require insulin For Type I patients

Step 1 Calculate Total Daily Insulin = 0.5 units x weight (kg). EXAMPLE. If a patient weighs 100 kg, the total daily insulin = 50 units/day If the patient is very active, has decreased creatinine clearance, or is on diabetic medications, then consider a lower weight dose (ie 0.3 units x weight (kg)). EXAMPLE 100 kg patient total insulin dose = 30 units/day. * Note: if a patient was started on insulin in the hospital via sliding scale – you may use the total amount of required insulin/day for the total daily insulin

Step 2 Split Total Insulin dose 50:50 between basal and bolus insulin 50% of dose is basal 50% of dose is bolus Further divide bolus insulin into 1/3 for 3 meal coverage.

Example using Glargine or Determire once daily dosing for Basal Insulin for a 100 kg person Total Insulin Dose = 50 units Mealtime or Bolus insulin (lispro, aspart, gluisine, regular) 25 Units Breakfast 8 Units Lunch Dinner Basal (Glargine or Determire) Insulin Bedtime Advantage – Tighter glucose control Disadvantage – giving more # of shots a day and monitoring glucose (pricking finger) more frequently.

Question? Calculate Insulin dosing for a 60 kg person using Glargine Basal Insulin and Regular Bolus insulin Total Insulin Dose = 30 Units Total Daily Glargine Insulin is 15 Units & Total Regular Insulin is 15 Units Regular insulin: 5 Units before Breakfast, 5 Units before Lunch, 5U before Dinner. Glargine 15 Units at bedtime. *Note: glargine should not be mixed in a syringe with other insulins.

Insulin Titration Have the patient check glucose readings at least 3 times a day in the log book – goal (fasting 90-120) and (3 hour post meal <160). If fasting blood glucose is consistently >120-130, increase the basal insulin (NPH or glargine, determir) by 2-4 units a week. If 2-3 hour post meal is consistently > 160, increase bolus insulin (lispro, aspart, gluisine, regular) by 2-4 units Example – if 3 hour post breakfast is consistently 200, however, all other glucose readings are well controlled…increase the pre-breakfast bolus insulin by 2-4 units

What about the high readings?

If the patient has persistent high glucose readings despite multiple titrations of insulin, think of: Incorrect Insulin Administration (Watch the patient’s technique in your office) Drawing up air and injecting it (instead of insulin) Not injecting the insulin SC Not rotating injection sites Dietary Non-compliance, weight gain Insulin Non-compliance/Skipping Doses Infection False readings – re-check glucometer & strips, check A1c and compare home glucose reading with clinic glucometer Outdated insulin or insulin exposed to extreme temps.

And the low readings?

If the patient has low readings, think of False readings – re-check glucometer & strips, check A1c and compare home glucose reading with clinic glucometer Insulin overdose No PO intake, change in eating habits Weight loss (chronic low readings) Renal failure (acute if sudden hypoglycemia on same dose of insulin) ***Rapid acting insulin and long acting insulin are both clear – have the patient label on with an elastic band or marker or store them separately to avoid medication errors.

Summary

Take Home Message Insulin Initiation Insulin Titration Better to start lower and titrate upwards than have a patient experience hypoglycemia (especially in older patients) Insulin Titration It takes time and constant titration to get patient at goal Follow patients closely (phone, e-mail) for insulin titration. Make sure the patient has a phone number to call with any questions or concerns. Educate the patient on the sign/symptoms & treatment of hyper & hypoglycemia Know when to refer the patient to a diabetes specialist

References Joslin Diabetes Center & Joslin Clinic Clinical Guideline for Pharmacological Management of Type 2 Diabetes 1/09/2009 www.professionaled.joslin.org Joslin E-Z start Resource Manual for Primary Care Practices Uptodate.com

Learning Outcomes for PD Lab Stations Effectively dose and titrate insulin for the cases given Demonstrate correct drawing up insulin and injection of insulin Be able to instruct patients on this technique Demonstrate correct technique of checking a capillary blood glucose Identify the signs and symptoms of hyperglycemia and hypoglycemia