Insulin therapy

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Insulin therapy
Niloufar Ansari, Pharm. D.
South Tehran Health Center, Tehran University of
Medical Sciences
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The breakthrough Toronto 1921 Banting Best
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Proposed Algorithm of therapy for Type 2 Diabetes
Inadequate Non pharmacological therapy

• Severe symptoms
• Severe hyperglycaemia
• Ketosis
• pregnancy

2 oral agents
3 oral agents
1oral agent
Add Insulin Earlier in the Algorithm
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Advantages of Insulin Therapy

• Oldest of the currently available medications,
  has the most clinical experience
• Most effective of the diabetes medications in
  lowering glycemia
• Can decrease any level of elevated HbA1c
• No maximum dose of insulin beyond which a
  therapeutic effect will not occur
• Beneficial effects on triglyceride and HDL
  cholesterol levels

Nathan DM et al. Diabetes Care 200629(8)1963-72.
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Disadvantages of Insulin Therapy

• Weight gain 2-4 kg
• May adversely affect cardiovascular health
• Hypoglycemia
• However, rates of severe hypoglycemia in patients
  with type 2 diabetes are low
• Type 1 DM 61 events per 100 patient-years
• Type 2 DM 1-3 events per 100 patient-years

Nathan DM et al. Diabetes Care 200629(8)1963-72.
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Types of Insulin

• 1. Rapid-acting
• 2. Short-acting
• 3. Intermediate-acting
• 4. Premixed
• 5. Long-acting
• 6. Extended long-acting

(Lispro, Aspart)
(Regular)
(NPH)
(70/30)
(Lantus)
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Pharmacokinetics of Current Insulin Preparations

• Effective
• Onset Peak Duration
• Insulin lispro lt15 min 1 hr 3 hr
• Regular 0.5-1 hr 2-3 hr 3-6 hr
• NPH/Lente 2-4 hr 7-8 hr 10-12 hr
• Ultralente 4 hr Varies 18-20 hr
• Insulin glargine 1-2 hr Flat/Predictable 24 hr
• Investigational

Barnett AH, Owens DR. Lancet. 199734997-51.
White JR, et al. Postgrad Med. 199710158-70.
Kahn CR, Schechter Y. In Goodman and Gilmans
The Pharmacological Basis of Therapeutics.
19901463-1495. Coates PA, et al. Diabetes.
199544(Suppl 1)130A.
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Summary of availableinsulin preparations
Agent Type / Administration Glucose lowering Glucose lowering
Agent Type / Administration Basal Post-meal
NPH Intermediate-acting human Once or twice daily at bedtime breakfast ?
Detemir Long-acting analogue Once or twice daily at bedtime breakfast ?
Glargine Long-acting analogue Once daily at bedtime or before breakfast ?
Premixed Human or analogue mix Twice daily before breakfast and dinner ? ?
Regular Fast-acting human Before meals ?
Aspart, glulisine, lispro Rapid-acting analogue Before meals ?
Inhaled insulin Rapid-acting human Before meals ?
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Insulin Pens

• NovoMix30
• 30 insulin aspart in a soluble fraction and 70
  insulin aspart crystallised with protamine
• NovoRapid
• Insulin aspart
• Insulatard
• NPH

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Insulin Pens
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Intelligent Devices

• Pumps
• Smart Phones
• Meters
• A central reporting station where data is
  filtered for minor versus major problems and who
  is to be alerted (user, guardian, MD/RN)

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Insulin
Delivery
Insulin syringes
We are here!
Pumps
Pens
Closed Loop
Connectivity
Open Loop
Data Management
Advice/Feedback
Monitoring
Home Monitors
Clinic Monitoring
HCP
Self Management
Automation
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Injection Techniques
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Sites of injection

• Arms ?
• Legs ?
• Buttocks ?
• Abdomen ?

• Easy access
• Ample subcutaneous tissue
• Absorption is not affected by exercise.

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Side Effects

• Hypoglycaemia
• - 15-15-15 rule
• - Dextrose 50
• - Glucagon
• 2. Allergy
• - Local allergy redness, swelling and
  itching at the site of injection
• General allergic reaction sweating, vomiting,
  breathing difficulties, rapid heart beat, feeling
  dizzy
• 3. Lipodystrophy

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The ADA Treatment Algorithm for
the Initiation and Adjustment of Insulin
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Normal physiologic patterns of glucose and
insulin secretion in our body
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• The rapid early rise of insulin secretion in
  response to a meal is critical,
• because
• it ensures the prompt inhibition of endogenous
  glucose production by the liver
• disposal of the mealtime carbohydrate load, thus
  limiting postprandial glucose excursions.

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Initiating and Adjusting Insulin
Hypoglycemia or FG gt3.89 mmol/l (70 mg/dl)
Reduce bedtime dose by 4 units (or 10 if dose
gt60 units)
Target range 3.89-7.22 mmol/L (70-130
mg/dL)
If HbA1c ?7...
If fasting BG in target range, check BG before
lunch, dinner, and bed. Depending on BG results,
add second injection (can usually begin with 4
units and adjust by 2 units every 3 days until BG
in range)
Continue regimen check HbA1c every 3 months
Recheck pre-meal BG levels and if out of range,
may need to add another injection if HbA1c
continues to be out of range, check 2-hr
postprandial levels and adjust preprandial
rapid-acting insulin
Continue regimen check HbA1c every 3 months
Nathan DM et al. Diabetes Care.
200629(8)1963-72.
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Step One
Hypoglycemia or FG gt3.89 mmol/l (70 mg/dl)
Reduce bedtime dose by 4 units (or 10 if dose
gt60 units)
Target range 3.89-7.22 mmol/L (70-130
mg/dL)
If HbA1c ?7...
If fasting BG in target range, check BG before
lunch, dinner, and bed. Depending on BG results,
add second injection (can usually begin with 4
units and adjust by 2 units every 3 days until BG
in range)
Continue regimen check HbA1c every 3 months
Recheck pre-meal BG levels and if out of range,
may need to add another injection if HbA1c
continues to be out of range, check 2-hr
postprandial levels and adjust preprandial
rapid-acting insulin
Continue regimen check HbA1c every 3 months
Nathan DM et al. Diabetes Care.
200629(8)1963-72.
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Step One Initiating Insulin

• Start with either
• Bedtime intermediate-acting insulin or
• Bedtime or morning long-acting insulin

Insulin regimens should be designed taking
lifestyle and meal schedules into account
Nathan DM et al. Diabetes Care 200629(8)1963-72.
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Step One Initiating Insulin, contd

• Check fasting glucose and increase dose until in
  target range
• Target range 3.89-7.22 mmol/l (70-130 mg/dl)
• Typical dose increase is 2 units every 3 days,
  but if fasting glucose gt10 mmol/l (gt180 mg/dl),
  can increase by large increments (e.g., 4 units
  every 3 days)

Nathan DM et al. Diabetes Care 200629(8)1963-72.
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Step One Initiating Insulin, contd

• If hypoglycemia occurs or if fasting glucose lt
  3.89 mmol/l (70 mg/dl)
• Reduce bedtime dose by 4 units or 10
  if dose gt60 units

Nathan DM et al. Diabetes Care 200629(8)1963-72.
While using basal insulin alone,never stop or
reduce ongoing oral therapy
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After 2-3 Months

• If HbA1c is lt7...
• Continue regimen and check HbA1c every 3 months
• If HbA1c is 7...
• Move to Step Two

Nathan DM et al. Diabetes Care 200629(8)1963-72.
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Step Two
Hypoglycemia or FG gt3.89 mmol/l (70 mg/dl)
Reduce bedtime dose by 4 units (or 10 if dose
gt60 units)
Target range 3.89-7.22 mmol/L (70-130
mg/dL)
If HbA1c ?7...
If fasting BG in target range, check BG before
lunch, dinner, and bed. Depending on BG results,
add second injection (can usually begin with 4
units and adjust by 2 units every 3 days until BG
in range)
Continue regimen check HbA1c every 3 months
Recheck pre-meal BG levels and if out of range,
may need to add another injection if HbA1c
continues to be out of range, check 2-hr
postprandial levels and adjust preprandial
rapid-acting insulin
Continue regimen check HbA1c every 3 months
Nathan DM et al. Diabetes Care.
200629(8)1963-72.
32
Step Two Intensifying Insulin

• If fasting blood glucose levels are in target
  range but HbA1c 7, check blood glucose before
  lunch, dinner, and bed and add a second
  injection
• If pre-lunch blood glucose is out of range,
• add rapid-acting insulin at breakfast
• If pre-dinner blood glucose is out of range,
• add NPH insulin at breakfast or rapid-acting
  insulin at lunch
• If pre-bed blood glucose is out of range,
• add rapid-acting insulin at dinner

Nathan DM et al. Diabetes Care 200629(8)1963-72.
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Making Adjustments

• Can usually begin with 4 units and
  adjust by 2 units every 3 days until blood
  glucose is in range

When number of insulin Injections increase from
1-2..Stop or taper of insulin secretagogues
(sulfonylureas).
Nathan DM et al. Diabetes Care 200629(8)1963-72.
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After 2-3 Months

• If HbA1c is lt7...
• Continue regimen and check HbA1c every
  3 months
• If HbA1c is 7...
• Move to Step Three

Nathan DM et al. Diabetes Care 200629(8)1963-72.
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Step Three
Hypoglycemia or FG gt3.89 mmol/l (70 mg/dl)
Reduce bedtime dose by 4 units (or 10 if dose
gt60 units)
Target range 3.89-7.22 mmol/L (70-130
mg/dL)
If HbA1c ?7...
If fasting BG in target range, check BG before
lunch, dinner, and bed. Depending on BG results,
add second injection (can usually begin with 4
units and adjust by 2 units every 3 days until BG
in range)
Continue regimen check HbA1c every 3 months
Recheck pre-meal BG levels and if out of range,
may need to add another injection if HbA1c
continues to be out of range, check 2-hr
postprandial levels and adjust preprandial
rapid-acting insulin
Continue regimen check HbA1c every 3 months
Nathan DM et al. Diabetes Care.
200629(8)1963-72.
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Step Three Further Intensifying Insulin

• Recheck pre-meal blood glucose and if out of
  range, may need to add a third injection
• If HbA1c is still 7
• Check 2-hr postprandial levels
• Adjust preprandial rapid-acting insulin

Nathan DM et al. Diabetes Care 200629(8)1963-72.
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Premixed Insulin

• Not recommended during dose adjustment
• Can be used before breakfast and/or dinner if the
  proportion of rapid- and intermediate-acting
  insulin is similar to the fixed proportions
  available

Nathan DM et al. Diabetes Care 200629(8)1963-72.
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Key Take-Home Messages

• Insulin is the oldest, most studied, and most
  effective antihyperglycemic agent, but can cause
  weight gain (2-4 kg) and
  hypoglycemia
• Insulin analogues with longer, non-peaking
  profiles may decrease the risk of hypoglycemia
  compared with NPH insulin
• Premixed insulin is not recommended during dose
  adjustment

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Key Take-Home Messages, contd

• When initiating insulin, start with bedtime
  intermediate-acting insulin, or bedtime or
  morning long-acting insulin
• After 2-3 months, if FBG levels are in target
  range but HbA1c 7, check BG before lunch,
  dinner, and bed,and, depending on the results,
  add 2nd injection (stop sulfonylureas here)
• After 2-3 months, if pre-meal BG out of range,
  may need to add a 3rd injection
  if HbA1c is still 7 check 2-hr
  postprandial levels and adjust preprandial
  rapid-acting insulin.

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Control random sugar level by adjusting the prior
dose of regular insulin
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Monitoring

• 1. Fasting hyperglycemia
• - Check NPH bedtime dose
• - Down Phenomenon
• - Somogyi Effect
• ? Use Regular before dinner and NPH at bedtime

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Somogyi phenomenon

• Due to
• excess dose of night time insulin, or
• Night insulin taken early
• Peaks at 300 a.m hypoglycemia
• Counter regulatory hormones released in excess
• Resulting in over correction of hypoglycemia
• Fasting hyperglycemia
• Solution
• Check BSL AT 3 00 a.m
• Give long acting at 1100 p.m so peak comes later
• Reduce dose of night time insulin

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Dawn phenomenon

• Growth hormone surge at dawn raises insulin
  requirement.
• Night time insulin taken early, fades out before
  dawn.
• Fasting hyperglycemia
• Solution
• Give long acting insulin not before 11 00 p.m
• May need to increase dose of night time insulin

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Monitoring, contd

• 2. Midmorning hyperglycemia
• - Check fasting blood glucose
• 3. Sick day management
• ? Do not reduce insulin dose

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Pearls for practice

• Never try to control diabetes with oral
  hypoglycemic drugs / insulin without first
  ensuring strict diet control.
• Always bring fasting sugar to normal before
  trying to control post prandial / random blood
  sugar.
• Control any underlying infection/stressful
  condition vigorously.
• Keep meal timings regular with 6 hrs between the
  three meals.
• Do not inject NPH before 11 p.m.
• Keep number of calories during the meals same
  from day to day. The quantity and quality of diet
  should be same at same timings.
• Do not use sliding scale to calculate the dose of
  insulin.
• Use proper technique to inject s/c insulin.
• Ensure proper storage of insulin.

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References

• Koda-Kimble MA, Carlisle BA. Diabetes Mellitus.
  Applied Therapeutics, The Clinical Use of Drugs.
• McCulloch DK. General principles of insulin
  therapy in diabetes mellitus. UpToDate.
• Evans M, Schumm-Draeger PM, Vora J, King AB. A
  review of modern insulin analogue pharmacokinetic
  and pharmacodynamic profiles in type 2 diabetes
  improvements and limitations. Diabetes Obes Metab
  2011 13677.
• Swinnen SG, Hoekstra JB, DeVries JH. Diabetes
  Care. 2009 Nov32 Suppl 2S253-9. Diabetes Care.
  200932 (Suppl 2)S253-9.
• Roach P. New insulin analogues and routes of
  delivery pharmacodynamic and clinical
  considerations. Clin Pharmacokinet.
  200847595-610.
• http//www.novonordisk.com/diabetes/public/insulin
  pens/flexpen/default.asp

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Thank you all For Sparing your valuable
time Patient listening
Abr jungle, Shahroud, Iran