DM2 ADVANCEMENT TO INSULIN: When Patient Fails Oral Rx
Patty Glatt, MD 10/09
I. Initiating Single Basal Injection
Describe to patient as the "background" amount of insulin needed to run the fuel cells of their
body's motor; Mealtime insulin is the extra insulin needed to handle the calories eaten.
 Add Basal “Background” insulin to oral regimen when A1C> 7.5-8.0 or FBS> 130 on
maximum optimal oral regimen. Early use reduces CV/macrovascular complications.
Single basal dose sufficient when FBS elevated but orals control postprandial
 Basal therapy offers opportunity for patient efficacy, establish control FBS, transition
to prandial and MDI insulin.
 Oral DM agents: Continue MTF for weight control and insulin resistance. Caution
w/TZD with insulin may ↑CHF. SU: Usually ↓ reduce to ½ max dose or DC.
BLOOD GLUCOSE GOALS ON HOME MONITORING
Before meals: 90-130: w/o significant hypoglycemia
120-180: for elderly or patients with hypoglycemic unawareness
80-100: for those desiring tighter physiologic control
After meals: under 160; Recommended under 135
Bedtime: under 180; Recommended under 130
Basal Insulin Treat to Target (T2T) Protocol:
Achieves quicker A1C control with patient-driven titration. Avoids hypoglycemia
GOAL: Titrate to FBS 90-130 mg/dl. (May adjust to tighter goal ≤110 individually per MD
outside of protocol)
How?
1. Start with minimum 10 units once daily Lantus/Glargine®, or Levemir/Detemir® or
use guideline below to guide decision. For 100kg, on average needs 40-50 units ultimately.
Some start at 50% calculated for T2T.
2. ↑ by 2 units until FBS <130; Option to ↑ by 4 units for FBS >180.
When? ↑ insulin dose every 3-4 days (“twice a week- patient picks”)
Warn: Hypoglycemia: ↓ by 4U or 10-15% if pre-breakfast glucose <70 or 2AM < 100
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CALCULATING BASAL INSULIN DOSE (Usually dosed at bedtime)
0.5 U/kg normally
0.3 U/kg if concerned about risk of hypoglycemia (elderly, impaired renal, cardiac or
hepatic function)
0.7 U/kg for presumed high insulin resistance (obesity, post-CABG, open wounds)
II. Moving Beyond Single Basal Dosing
After Basal T2T goal is reached, if HgbA1C remains >8.0, on add pre-meal "Prandial"
insulin
PREMIXED INSULIN(Humalog ®75/25 or Novolog ®70/30):
Advantage of Premixed Insulins
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For patients unable to manage multiple dose injections for whatever reason
Improved control when Basal insufficient
Disadvantages of Premixed Insulins
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Must eat at regular times and consistent calories; Skipping meals may lead to hypoglycemia
Premixed insulin offers no flexibility in adjustment of rapid portion
PREMIXED INSULIN OPTIONS:
1.) Switch to single Premixed before dinner. Titrate Premixed T2T to 2hrpost prandial
BS (based on start of meal). Best when mostly elevated FBS and dinner or as initial Pre-mix when
dinner is highest meal.
2.) Advance to BID premixed Humalog®75/25 or Novolog ®70/30. Occasional use for
Humalog®50/50 for PM dose when more PM prandial insulin needed
3.) AM Premixed Humalog ®75/25 or Novolog ®70/30 or NPH+Lispro(Humalog®)
and PM (dinner or HS) NPH When most elevations are daytime only.
III. MDI (Multi-Dose Injection) Basal +Bolus Regimen:
Add pre-meal (Humalog®)Lispro, (Novolog®)Aspart, or (Apirdra)Glulisine® to single
meal; start with largest meal. Gradually add additional largest meals, one at a time, until
control. T2T for each prandial rapid insulin to 2hr postprandial.
Features:
 Test glucose before meal and 2 hours after meal (from first bite) being targeted. Adjust
twice a week until readings are within 40mg/dl of each other or goal achieved
 Basal insulin Glargine usually given at bedtime. Adjust until FBS at target
 Rapid-acting Lispro (Humalog) before each meal. May start with highest meal.
 Add supplemental Lispro(Humalog) meal bolus insulin ( see Correction Factors below)
if above target before giving prandial insulin
Benefits
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Can be used with Type 2 DM and Type 1
Assoc w/ improved glycemic control leading resulting in less microvascular ds
Patient not tied to rigid eating schedule as with fixed-split
Elimination of dietary restrictions for those who do CHO counting
Disadvantages
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Intensive management requires high level compliance and literacy to master
Frequent testing required or learning Carb counting
Starting Basal/Bolus Insulin Regimen
1. Calculate Total Daily Dose (TDD)-see box. [Alternative: 0.25-0.3 U/kg/d]
CALCULATE THE TDD: Calculate the TDD based on patient size for premixed insulin
Dialysis patient (regardless of BMI): 0.3 U/kg/d
Lean (BMI <25): 0.4 U/kg/d
Overweight (BMI 25-30): 0.5 U/kg/d
Obese (BMI >30): 0.6 U/kg/d
2. Basal =50% of TDD, usually at bedtime; alternatively 30% TDD as NPH pre-breakfast
and 20% TDD as NPH pre-dinner
3. Prandial (pre-meal) Bolus = 50% of TDD, as Lispro, Aspart, or Apirdra : 20% prebreakfast, 10% pre-lunch, and 20% pre-dinner. Alternative: Basal 40%; Premeal =
20% each
Alternative
Basal = 0.125units/kg/d
Pre-Breakfast Lispro= 0.025 units/kg/d
Pre-Lunch Lispro = 0.0125 units/kg/d
Pre-Dinner Lispro = 0.023 units/kg/d
Patient Self Adjustment Instructions:
SELF ADJUSTMENT FOR PREMIX AND MDI LISPRO
When? Every 3-4 days. Adjust one dose at a time, usually first targeting dinner control.
Target Goal: ↑ 1-2 units until at target goal 90-130 before meals.
WHEN?
Uncontrolled Pre-Meal BG
Before Breakfast Glucose
Before lunch
2 hr after Lunch
2 hr after Dinner
Bedtime Glucose
HOW MUCH?
If Blood Glucose
<20 below goal
At goal
over 5-10
over 11-19
>20 above goal
Adjust
Bedtime Basal
Before Breakfast Lispro or Breakfast
premixed
Before Lunch Lispro insulin or
Before Lunch Premixed insulin
Before Dinner Lispro or Before
Dinner premixed insulin
Before Dinner Lispro or
Before Dinner premixed
Adjust Insulin
↓ dose 3 Units or 10-15%
No Change
↑ dose 1 unit
↑ dose 2 units
↑ dose 3 Units
TARGET GOALS:
FBS, PREMEAL ≤ 130 ≥90 , Recommended ˂100
2 HR POSTPRANDIAL ˂160 -135; recommend goal ˂135
BEDTIME ˂130
HYPOGLYCEMIA ANY ˂70
http://care.diabetesjournals.org/content/32/1/193.full.pdf+html
http://clinical.diabetesjournals.org/content/23/2/78.full.pdf+html
http://care.diabetesjournals.org/content/31/7/1305.full.pdf+html
MISCELLANEOUS PRACTICE TIPS
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Fix lows values first. If only once or twice (not a pattern), ask about skipped
meals. Adjust insulin in response to a pattern, not in response to a single abnormal
value
Hypoglycemia: Review signs, symptoms, treatment and strategies for preventing
Give patients early opportunity to try a “dry practice insulin injection”
Offer pen devices to patients with low vision, poor hand control, true needle
phobia. Medi-Cal TAR approval feasible for all of these. PAR for CCHP.
Don’t underprescribe low dose syringes. Better to use 0.5 for T2T
NEVER THREATEN A PATIENT WITH INSULIN
CCHP limits Lantus to 60 cc/month.
Pens 5/box
IV. Pens and Needles
PEN DEVICES
Patient Selection:
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Poor Dexterity- OA, neuropathy - Approved indication
Mental or Cognitive impairment - Approved indication
Poor eyesight
- Approved indication
Poor adherence –Requires explanation for authorization
Needle Phobia –Requires explanation for authorization
Manufacturer
Product
Aventis-Sanofi
Solostar PrefilledPen Lantus (Glargine) *Once daily/ HS
$195
Solostar PrefilledPen Apidra (Glulisine)* 15 mins AC
Opticlick*
Most used in EU
*Order B-D Ultra Fine Needles 31g ,3/16"mini, 5/16"short; 29g 1/2"
standard
Reusuable
Timing
Cost
Novo Nordisk
Reusable
Novolog® Mix 70/30 FLEXPENǂ
15 mins AC
$195
Novolog ® (Aspart) FLEXPENǂ
10 mins AC
$195
ǂOrder NovoFine 30,32 disposable needles or B-D Ultra Fine Needles
31g,3/16", 5/16";29g 1/2" standard
Lilly
Humalog® Mix 75/25 Prefilled Pen 5 mins AC
$195
Humalog® (Lispro) Prefilled Pen
15 mins AC
$195
Humulin® N (NPH) Pen
30 mins AC
$140
Humulin® 70/30 (NPH/R)
30 mins AC
$140
*Order B-D Ultra Fine Needles 31g ,3/16", 5/16";[29g 1/2" original]
“Pre-filled” pens are disposable. All supplied 3ml=300 units/ pen or cartridge; 5 pen/per box. Max delivery is 60
units max per injection, except Solostar Lantus and Opticlick with max 80 units per injection
[Innolet Device with large dial and numbers for use with Novolin ®(NPH/Reg) - soon to be discontinued]
All covered on medical plans but require Prior Authorization/ Treatment Authorization Requests
Store all unopened cartridges in refrigerator until use or expiration date; Store open unrefrigerated pen cartridges
for 10-14 days.
Good cost alternative are Prefilled Syringes for selective patients e.g. learning impaired, family members
NEEDLES
Gauge: Thinness. Higher number refers to finer needle. Order highest gauge available for patient comfort
30, 31 (“microfine”) gauge: needles are painless
Lengths: Thin patients can use shorter needles. Obese patients need longer needles.
1/2" Standard ( comes in 29, 30, 31 gauge) for more obese patients
5/16” Short ( comes in 28, 29, 20, 31 gauge) for thinner patients
3/16" Mini May be most comfortable for the
Volume: Don’t underprescribe. Patient may not exceed their monthly insurance allotment
0.3cc =Low dose - up to 30 units. Best visibility if low dose used. May exceed dose if T2T pt.
0.5cc = Low dose- up to 50 units. Best for starting T2T to avoid running out of syringes
1.0 cc = Standard- up to 100 units. Best if obeseT2T and likely will need high dose
V. Talking Points:
OVERCOMING BARRIERS TO STARTING INSULIN TX
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Using insulin does not mean failure. "You haven't failed' your pancreas has."
Educate early that diabetes is a progressive disease; prepare your patient that
most patients will eventually need insulin.
Oral medication only work when the body makes enough insulin.
Starting Insulin early is about reducing complications over 10 years (death, MI,
Stroke, amputation). We can all agree on a goal to live a long healthy life.
Insulin allows a person the freedom to eat a relatively “normal” diet again
The patient does not have to choose between good control and foods they enjoy
Insulin is the only “natural therapy” we have
Just one shot a day of insulin may be sufficient
Insulin does not require refrigeration
Starting insulin does not cause complications; untreated advanced disease does.
INSULIN ALWAYS WORKS
VI. Addendum
Bolus Pre-prandial Insulin Correction Dose
Calculating the Insulin Sensitivity Factor:
Adjust blood glucose before/between meals as needed for deviations from goal.
Approximation if patient is not well controlled on current insulin regimen.
APPROXIMATION OF INSULIN SENSITIVITY FACTORS:
Patient Characteristic
Highly insulin sensitive and/or bad kidneys
Normally insulin sensitive
Mild insulin resistance
BMI> 25
Moderate insulin resistance BMI>30
Severe insulin resistance
BMI>40
Amount ↓BG/1U Lispro
Lower 60-100 mg/dl
Lower 50 mg/dl
Lower 30 mg/dl
Lower 20 mg/dl
Lower <10 mg/dl
"RULE OF 1800"
For patients well controlled, use the Rule of 1800 for a more precise patient-specific
value. This is the amount of Lispro needed to bring current BG down to target BG.
“Rule of 1800” Insulin Sensitivity Factor: To estimate expected drop in blood glucose for
each unit of Lispro insulin, use the “1800 Rule”
[Feasible to calculate only when pt. in reasonable control on known insulin regimen]
1.) To calculate the Correction Factor: Divide 1800 by total current Total Daily
Dose insulin (TDD)= glucose mg/dl point drop for every unit of Lispro insulin.
2.) Current BG – Target BG (110)= # points over target.
3.) Divide this by “correction factor” (round # as needed).
INSULIN:CARBOHYDRATE CORRECTION FACTOR
 To estimate the insulin required to cover the carbohydrate load of an upcoming meal.
(CHO counting). Method used for intensive Bolus + 3X Prandial
 Package labels and food lists with carbohydrate grams and portions sizes assist with
this.
I:C ratio is the amount of carbohydrate covered by one unit of rapid-acting insulin
analog (Lispro, Aspart). The insulin-to-carbohydrate ratio can be determined using the
500 rule (see below), in which the total daily dose of insulin (TDD) is divided by 500.
Typically, insulin-to-carbohydrate ratios are in the range of 1U: 10-15 gram of
carbohydrate.
This method can be modified for patients who prefer a simpler method of counting
carbohydrates or food intake. Patients round their carbohydrate choices to a 15 g portion
size and count their carbohydrates in denominations of portions rather than grams. An
example would be 1 unit of insulin per 1 portion of carbohydrate.
The Carbohydrate Coverage “500 Rule”:
Gives an approximation for how many grams of CHO will be covered by 1U of Lispro
insulin.
Divide 500 by the TDD of insulin (basal + bolus) to determine how many grams of
carbohydrate will be covered by 1U of Lispro. This is this individuals “correction factor”.
EXAMPLES OF CORECTION FACTORS
Calculating Carbohydrate Coverage with “500 rule”
Example: Pt uses total 30 units per day (15 units Glargine and 15 units Lispro):
500/30= 17 grams carbohydrate covered by 1 unit of Lispro
Therefore, for this patient, there CHO: Lispro insulin ratio is 17:1
Calculating Insulin Sensitivity Factor- Example:
Joe typically uses 30 units of glargine at bedtime, 10 units of lispro at breakfast, 5 units at
lunch, and 15 units at dinner.
TDD= 30glargine = 30lispro = 60 units insulin/day
1800/60 = 30
Therefore every 1 unit of Lispro should drop Joe’s blood glucose 30 mg/dl.
Or stated another way, for Joe, his insulin sensitivity correction factor is 30 mg/dl for
each unit of Novolog (Lispro).This can be used to estimate what supplemental dose Joe
will need for a pre-meal correction dose in addition to his usual dose if his pre-meal
glucose value is exceeds target value.
Calculating Bolus- Example:
Joe has a tooth infection. His pre-lunch blood sugar has shot up to 240 from his usual
120. He needs a correction factor for 120mg/dl. Therefore, he needs 120mg/dl divided by
30mg/dl per 1 unit = 4 units Novolog for correction.. Therefore Joe’s dose will be his usual
5 + 4 = 9 units Novolog before eating lunch.
Example:
Calculating Pre-Prandial Correction with CHO counting and Bolus Correction:
By way of example, consider a patient who has a target blood sugar before meals of 110,
premeal glucose of 170, insulin-to-carbohydrate ratio of 1:15, and an insulin sensitivity
factor of 1:30. This person is about to eat a meal estimated to contain 60 g of
carbohydrate. He currently takes a dose of Glargine/Lantus every evening and a rapidacting analog (lispro or aspart) before each meal. With the I:C ratio of 1:15 and 60 g of
carbohydrate intake, this patient would require 4 units of rapid-acting insulin to cover
the carbohydrates at this meal. With a premeal glucose of 170, target glucose of 110 and a
1:30 insulin sensitivity factor, an additional 2 units would be required as the correction
factor. Four units of lispro or aspart will be needed to cover the carbohydrate intake, and
an additional 2 units will be needed as a correction factor based on the premeal glucose,
for a total dose of 6 units of lispro or aspart.