INSULIN DOSING

• ACRONYMS AND DEFINITIONS

• ADA - American Diabetes Association
• Basal Insulin - Long- and Intermediate-acting insulins used to supply constant blood levels of insulin activity
• Carb- carbohydrate
• T1DM - Type 1 diabetes
• T2DM - Type 2 diabetes
• FDA - U.S. Food and Drug Administration
• Hypoglycemia - low blood sugar
• Multidose insulin regimen - Insulin regimens that involve a basal insulin and a premeal insulin given at meals
• Premeal Insulin - also called “prandial” insulin. Rapid and short-acting insulins given at mealtime for short burst of insulin.
• Total daily dose of insulin - Sum of premeal and basal insulin given in a day
• Units/kg/day - units of insulin per kilogram of body weight per day
• USDA - United States Department of Agriculture
• 1 kilogram = 2.2 pounds

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• IMPORTANT POINTS ABOUT DOSING INSULIN

• Overview
• There are a number of different ways to dose insulin
• The appropriate method for individual patients will depend on a number of factors including patient education, patient motivation, diabetes control, and resources


• Low blood sugar (Hypoglycemia)
• The main concern in most patients when initiating an insulin regimen is the occurrence of low blood sugars
• Patients need to understand that when they are starting and adjusting insulin, there is an increased risk for low blood sugars
• A number of things can affect this risk including variations in eating patterns, sensitivity to insulin, and variations in activity level


• Measures to help prevent low blood sugars
• Start low and go slow - patients naïve to insulin should start at the lower end of dosing ranges
• When using a multidose regimen, adjust only one of the regimens every 3 days and alternate between the two (see below for more)
• The correction factor can help to keep blood sugars from running too high while the insulin regimen is being adjusted
• Try to avoid insulin doses outside of the regimen as this may lead to overcorrections
• In a multidose regimen, it is important to consume a consistent diet of three meals a day while keeping the number of carbohydrates in each meal about the same

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• INSULIN CATEGORIES

• For dosing purposes, insulins can be divided into two categories:
• Basal insulins
• Premeal insulin (prandial insulin)

• BASAL INSULINS
• Basal insulins provide a steady concentration of insulin in the bloodstream over a number of hours
• They do not act quickly


• Basal Insulin include the following intermediate and long-acting insulins:
• Humulin® N (NPH)
• Novolin® N (NPH)
• Basaglar® (insulin glargine)
• Lantus® (insulin glargine)
• Levemir® (insulin detemir)
• Toujeo® (insulin glargine)
• Tresiba® (insulin degludec)


• PREMEAL INSULINS
• Premeal insulins provide a burst of insulin that acts quickly
• They are typically used 5 - 30 minutes before meals


• Premeal insulins include the following rapid and short-acting insulins:
• Admelog® (insulin lispro)
• Afrezza® (inhaled insulin)
• Apidra® (insulin glulisine)
• Fiasp® (insulin aspart)
• Humalog® (insulin lispro)
• Novolog® (insulin aspart)
• Humulin® R (regular)
• Novolin® R (regular)


• Insulin property chart - review of available insulins including properties, storage, etc.

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• BLOOD SUGAR GOALS

• See ADA blood sugar goals in DM

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• INSULIN DOSING IN TYPE 2 DIABETES

• See ADA insulin recommendations in T2DM

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• STARTING INSULIN IN TYPE 1 DIABETES (T1DM)

• ADA recommendations
• The ADA recommends the following for T1DM patients:
• Multidose injections (3-4 a day) of basal and premeal insulin, or insulin pump therapy
• Patients should match premeal insulin to carbohydrate intake, premeal blood glucose levels, and anticipated activity [10]

• General dosing guidelines
• Daily dose of insulin
• Insulin dosing in T1DM will vary based on patient's age, weight, and residual pancreatic insulin activity
• T1DM patients will typically require a total daily insulin dose of 0.4 - 1.0 units/kg/day
• T1DM patients may experience a "honeymoon phase" after starting insulin where lower doses are effective [7,13]


• Determining doses of basal and premeal insulin
• After the total daily dose is determined, insulin is typically administered as follows:
• Basal insulin - given as half of the total daily dose
• Premeal insulin - half of the total daily dose divided into thirds and given before each meal
• NOTE: When first starting therapy, it is recommended that the initial basal dose be reduced by 20 - 30% to prevent low blood sugar (hypoglycemia) [11,19]


• Example:
• Patient weighs 80 kg
• Total daily dose = 80 kg X (0.5 units/kg/d) = 40 units per day
• Basal insulin = 1/2 X 40 units = 20 units of basal per day*
• Premeal Insulin = 1/2 X 40 units = 20 units ÷ 3 = approximately 7 units before each meal
• * If patient is just starting therapy, the initial basal dose should be reduced by 20 - 30%. In our example: 20 units X 0.20 = 4 units, so initial basal dose would be 20 - 4 = 16 units

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• ADJUSTING BASAL INSULIN

• Overview
• There a number of ways to adjust basal insulin
• A common and straightforward method is presented here


• Adjusting basal insulin regimens
• This method can be used for the following:
• Adjusting once-a-day basal regimens in T2DM
• Adjusting basal insulin in multidose (basal and premeal) regimens in T1DM and T2DM


• Steps:
• 1. Measure fasting blood sugar (no calories for 8 hours) for previous three consecutive days
• 2. Calculate the average of the three fasting blood sugars
• 3. Adjust basal insulin dose based on the table below
• 4. Repeat steps 1-3 until target range (80 - 99) is achieved

Reference [12]

Fasting blood sugar (mg/dl) average over 3 days	Adjustment to basal insulin dose (units of insulin)
≥ 180	add 8 units
160 - 179	add 6 units
140 - 159	add 4 units
120 - 139	add 2 units
100 - 119	add 1 unit
80 - 99	no change
60 - 79	subtract 2 units
< 60	subtract 4 or more units

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• ADJUSTING PREMEAL INSULIN (SCALE METHOD)

• Scale method
• With the scale method, premeal insulin is adjusted based on a scale
• Patients should try to consume the same amount of carbohydrates at each meal (a typical amount is about 60 grams a meal and 15 grams for a bedtime snack)
• Carbohydrate goals vary by individual (see carbohydrate information below)


• Steps:
• 1. Measure blood sugar fasting (pre-breakfast), pre-lunch, pre-dinner, and pre-bedtime snack for previous three consecutive days
• 2. Average the pre-lunch, pre-dinner and pre-bedtime values separately
• 3. Adjust the premeal insulin dose based on the table below
• 4. Repeat steps 1-3 until target range is achieved
• 5. A Correction Factor (see below) should also be incorporated when blood sugars are checked

Reference [12]

If pre-lunch average is not in desired range, adjust pre-breakfast dose If pre-dinner average is not in desired range, adjust pre-lunch dose If pre-bedtime snack average is not in desired range, adjust pre-dinner dose
Premeal blood sugar (mg/dl) average over 3 days	Adjustment to premeal insulin dose
≥ 180	add 3 units
160 - 179	add 2 units
140 - 159	add 2 units
120 - 139	add 1 units
100 - 119	maintain dose (desired range)
80 - 99	subtract 1 unit
60 - 79	subtract 2 units
< 60	subtract 4 or more units

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• ADJUSTING PREMEAL INSULIN (CARBOHYDRATE COUNTING)

• Carbohydrate counting
• In carbohydrate counting, premeal insulin is adjusted based on the amount of carbohydrates to be consumed in each meal
• The carbohydrate counting method is used to determine the amount of carbohydrates in a meal
• An insulin to carbohydrate ratio (ex. 1 unit/10g of carb) is used to calculate the premeal insulin dose
• A typical starting ratio is 1 unit of premeal insulin for every 10 grams of carbs to be consumed
• An individual may have different carbohydrate ratios for breakfast, lunch, and dinner because a person's response to insulin may vary throughout the day


• Example:
• 60 grams of carbs to be consumed for lunch
• Patient's ratio is 1 unit of insulin for every 10 grams of carbs
• Patient injects 6 units of premeal insulin before eating meal


• Steps for adjusting an insulin-to-carb ratio
• 1. Calculate the number of carbs to be consumed in a meal using carbohydrate counting
• 2. Dose premeal insulin based on number of carbs in a meal (typical starting point is 1 unit of premeal insulin for every 10 grams of carbs)
• 3. Measure blood sugar fasting (pre-breakfast), pre-lunch, pre-dinner, and pre-bedtime snack for previous three consecutive days
• 4. Average the pre-lunch, pre-dinner and pre-bedtime snack blood sugar values separately
• 5. Adjust the carbohydrate to insulin ratio as instructed below:


• If pre-lunch average is not in desired range (80 - 120 mg/dl), adjust breakfast ratio
• If pre-dinner average is not in desired range (80 - 120 mg/dl), adjust lunch ratio
• If pre-bedtime snack average is not in desired range (80 - 120 mg/dl), adjust dinner ratio


• If average blood sugar is > 120 mg/dl, adjust ratio by subtracting 2-3g of carbohydrate


• Example:
• Current ratio 1 unit / 10g of carb
• Pre-lunch average > 120 mg/dl
• Change breakfast ratio to 1 unit / 7g of carb


• If average blood sugar is < 80 mg/dl, adjust ratio by adding 2-3g of carbohydrate


• Example:
• Current ratio 1 unit / 10g of carb
• Pre-bedtime snack average < 80 mg/dl
• Change dinner ratio to 1 unit / 13g of carb


• If average blood sugar is 80 - 120 mg/dl, do not adjust ratio


• 6. Repeat steps 1-5 until appropriate ratios are determined [3,4]
• 7. A Correction Factor (see below) should also be incorporated when blood sugars are checked

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• ADJUSTING PREMEAL AND BASAL INSULINS CONCURRENTLY

• When adjusting premeal and basal insulins concurrently, adjustments to one regimen may affect the other regimen. This can lead to overcorrections and hypoglycemia.
• Alternating between regimens may help prevent overcorrections

• Example:
• Day 3 - adjust basal
• Day 6 - adjust premeal
• Day 9 - adjust basal
• Day 12 - adjust premeal, and so on...

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• CORRECTION FACTOR

• Correction factor
• When blood sugar checks are high, a correction factor should be used with premeal insulin
• The correction factor supplies supplemental insulin to account for the elevated blood sugar
• Insulin used in the correction factor should not be included in calculations for adjusting premeal or basal insulin
• There are several methods that can be used to determine the correction factor
• When first starting therapy, the ideal total daily insulin dose will not be known, so the flat method is preferred over the individual method



• FLAT METHOD

  • One unit of extra insulin is added for every 25 mg/dl that blood sugar is above the upper limit of the desired range
  
  
  • Example:
  • Pre-lunch blood sugar is 200 mg/dl
  • upper limit of desired range is 120 mg/dl
  • 200 - 120 = 80 mg/dl above desired range
  • 80 mg/dl ÷ 25 mg/dl = approximately 3
  • add 3 extra units to premeal dose
  
  

• INDIVIDUAL METHOD

• The individual method uses a patient's total daily insulin dose to calculate a correction factor
• The correction factor is calculated differently for regular insulins (Humulin R, Novolin R) and rapid insulins (Novolog, Humalog, Apidra, Fiasp)


• For Regular insulin (Humulin R, Novolin R)
• 1. Divide 1500 by the patient's total daily dose of insulin
• 2. The result will equal the estimated drop in blood sugar (in mg/dl) from 1 unit of regular insulin
• For Rapid insulin (Novolog, Humalog, Apidra, Fiasp)
• 1. Divide 1800 by the patient's total daily dose of insulin
• 2. The result will equal the estimated drop in blood sugar (in mg/dl) from 1 unit of rapid insulin [4,12]


• Example:
• Patient's total daily dose of insulin (premeal + basal) is 60 units
• Patient uses regular insulin as premeal insulin
• 1500/60 = 25
• Patient can expect that for every 1 unit of regular insulin they inject, their blood sugar will come down 25 mg/dl


• Once the correction factor is calculated, the patient can then figure out how much insulin to supplement


• Example:
• Patient from above: correction factor is 25 mg/dl
• Patient checks pre-lunch blood sugar and it is 175 mg/dl (desired range 80 - 120 mg/dl)
• 175 - 120 = 55 mg/dl
• 55/25 = approximately 2
• Patient would add 2 extra units of regular insulin to premeal dose

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• EXERCISE AND INSULIN DOSING

• See exercise and insulin page

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• SLIDING SCALE INSULIN

• Sliding Scale Insulin involves checking the blood sugar and dosing the insulin (typically rapid or short-acting) based on the blood sugar value
• Doctors use a number of different regimens depending on the patient and their sensitivity to insulin. The example below is a common starting regimen.

Blood sugar (mg/dl)	Insulin dose in units of rapid or short-acting
< 150	0
150 - 200	2
201 - 250	4
251 - 300	6
301 - 350	8
351 - 400	10
401 - 450	12
> 450	14

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• CONVERTING BETWEEN INSULIN BRANDS AND TYPES

• Overview
• It's important to note that patients may respond differently to different insulin brands and types
• The conversion guidelines presented here are meant to serve as a starting point, but they will not necessarily achieve equivalent results across all patient populations
• All patients should increase their blood sugar monitoring when switching insulins to determine the effects of the new regimen



• Converting between rapid-acting and short-acting insulin

• When converting between rapid-acting and short-acting insulins, the dose typically remains the same
• Rapid-acting insulins act quicker (within 10 - 30 minutes) than short-acting insulins (within 30 - 60 minutes); therefore, the timing of the dose should be adjusted
• Rapid-acting insulins have a shorter duration of action than short-acting insulins (3 - 5 hours vs 6 - 8 hours). This may mean patients switching to rapid-acting insulins from short-acting insulins may require more basal insulin to maintain blood sugar control, and vice versa.
• Conversions for inhaled insulin are discussed here - inhaled insulin dosing



• Converting between Lantus/Basaglar (Insulin glargine) and NPH

• Once-a-day NPH to Lantus/Basaglar
• Dose remains the same


• Twice-a-day NPH to Lantus/Basaglar
• Lantus/Basaglar dose is 80% of total daily NPH dose
• Example:
• Patient's NPH dose is 30 units twice-a-day
• Total daily NPH dose is 60 units
• To convert to Lantus/Basaglar: 60 units X 0.80 = 48 units
• Daily Lantus/Basaglar dose will be 48 units [19]


• Lantus® to twice-a-day NPH
• Lantus/Basaglar dose would be equivalent to about 80% of daily NPH dose
• Example:
• Patient's Lantus/Basaglar dose is 50 units a day
• To convert to NPH: 50 units = (0.80)(Daily NPH dose); Daily NPH dose = 50/0.80 = 62.5 units
• Daily NPH dose would be ∼ 62 units given in 2 divided doses
• NOTE: Patients with hypoglycemia issues may want to leave the initial daily NPH dose the same as the Lantus/Basaglar dose



• Converting between Lantus/Basaglar (Insulin glargine) and Levemir® (Insulin detemir)

• Daily dose remains the same [20]



• Converting between Lantus/Basaglar (Insulin glargine) and Toujeo® (Insulin glargine)

• Lantus/Basaglar to Toujeo
• When going from Lantus/Basaglar to Toujeo, the daily dose remains the same
• Expect that a higher daily dose of Toujeo® will be needed to maintain the same level of glycemic control as an equivalent dose of Lantus/Basaglar
• In a multidose study, the glucose-lowering effect of Toujeo® was about 27% lower than that of an equivalent dose of Lantus® [21]


• Toujeo to Lantus/Basaglar
• When going from Toujeo to Lantus/Basaglar, the Lantus/Basaglar dose should be started at 80% of the Toujeo dose in order to avoid hypoglycemia
• Lantus/Basaglar is more potent than Toujeo, therefore, an equally effective Lantus/Basaglar dose will likely be lower [19,23]
• Example:
• Patient's Toujeo dose is 60 units a day
• To convert to Lantus/Basaglar: 60 units X 0.80 = 48 units
• Daily Lantus/Basaglar dose will be 48 units



• Converting between Levemir® (Insulin detemir) and NPH

• Daily dose remains the same [20]



• Converting between Toujeo® (Insulin glargine) and NPH

• Twice-a-day NPH to Toujeo®
• Toujeo® dose is 80% of total daily NPH dose
• Example:
• Patient's NPH dose is 30 units twice-a-day
• Total daily NPH dose is 60 units
• To convert to Toujeo: 60 units X 0.80 = 48 units
• Daily Toujeo dose will be 48 units [19]



• Converting between Toujeo® (Insulin glargine) and Levemir® (Insulin detemir)

• Daily dose remains the same [21]



• Converting between Tresiba® (insulin degludec) and all other long- and intermediate-acting insulins

• Daily dose remains the same
• In trials comparing Tresiba to Lantus and Levemir, the glucose-lowering effect of Tresiba was equivalent to both insulins [22]

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• HYPOGLYCEMIA (LOW BLOOD SUGAR)

• See hypoglycemia

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• CARBOHYDRATE INFORMATION

• Carbohydrates and insulin
• It's important that diabetics who are taking insulin monitor their carbohydrate intake
• See the links below for more information on dieting and carbohydrates


• Carbohydrate counting - review of carbohydrate counting used in dosing premeal insulin
• Calories - review on calculating caloric requirements
• Diabetic diet - diabetic diet recommendations
• Carbohydrates - review of different carbohydrates found in foods

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• BIBLIOGRAPHY

• What is PMID?
• PI = Manufacturer's Package Insert

• #     PMID
  
• 1 - 18945920
• 2 - PMID: 10332663
• 3 - PMID: 18364392
• 4 - Braithwaite S: Case Study: Five Steps to Freedom: Dose Titration for Type 2 Diabetes Using Basal-Prandial-Correction Insulin Therapy. Clinical Diabetes Vol 23:1 p39-43 2005
• 5 - Kulkarni K: Carbohydrate Counting: A Practical Meal-Planning Option for People With Diabetes. Clinical Diabetes Vol 23:3 p120-122 2005
• 6 - PMID: 16915796
• 7 - PMID: 15616254
• 8 - PMID: 16921608
• 9 - PMID: 10378067
• 10 - PMID: 21193625
• 11 - PMID: 12734137
• 12 - PMID: 16847295
• 13 - Herbst K, Hirsch I Insulin Strategies for Primary Care Providers. Clinical Diabetes. Vol 20:1 p1-7 2002
• 14 - PMID: 17890232 - NEJM DM 2 study
• 15 - Hirsch I et al. A Real-World Approach to Insulin Therapy in Primary Care Practice. Clinical Diabetes. Vol 23:2 p78-86. 2005
• 16 - PMID: 18165339
• 17 - PMID: 12766131
• 18 - Glucagon PI
• 19 - Lantus PI
• 20 - Levemir PI
• 21 - Toujeo PI
• 22 - Tresiba PI
• 23 - Basaglar PI
• 24 - ADA 2015 Standards of Medical Care in Diabetes, Vol 38, Supplement 1, p. S46
• 25 - PMID 29222370 - ADA 2018 Standards of Medical Care in Diabetes