Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical...

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Insulin therapy Niloufar Ansari, Pharm. D. h Tehran Health Center, Tehran University of Medical Sc

Transcript of Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical...

Page 1: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Insulin therapy

Niloufar Ansari, Pharm. D.

South Tehran Health Center, Tehran University of Medical Sciences

Page 2: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

The breakthrough: Toronto 1921 – Banting & Best

Page 3: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.
Page 4: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Indications for Insulin Use in Type 2 DiabetesPregnancy (preferably prior to pregnancy)

Acute illness requiring hospitalization

Perioperative/intensive care unit setting

Postmyocardial infarction

High-dose glucocorticoid therapy

Inability to tolerate or contraindication to oral antiglycemic agents

Newly diagnosed type 2 diabetes with significantly elevated blood glucose levels (pts with severe symptoms or DKA)

Patient no longer achieving therapeutic goals on combination antiglycemic therapy

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InadequateNon pharmacological

therapy

InadequateNon pharmacological

therapy

1oral agent2 oralagents

3 oralagents

Add Insulin Earlier in the AlgorithmAdd Insulin Earlier in the Algorithm

•Severe symptoms

•Severe hyperglycaemia

•Ketosis

•pregnancy

Proposed Algorithm of therapy for Type 2 Diabetes

Page 6: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Advantages of Insulin TherapyAdvantages 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 2006;29(8):1963-72.

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Disadvantages of Insulin TherapyDisadvantages 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-yearsType 1 DM: 61 events per 100 patient-years

Type 2 DM: 1-3 events per 100 patient-yearsType 2 DM: 1-3 events per 100 patient-years

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

Page 8: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Types of InsulinTypes 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)

Page 9: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

EffectiveOnset Peak Duration

Insulin lispro <15 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

Pharmacokinetics of Current Insulin Preparations

Barnett AH, Owens DR. Lancet. 1997;349:97-51. White JR, et al. Postgrad Med. 1997;101:58-70. Kahn CR, Schechter Y. In: Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 1990:1463-1495. Coates PA, et al. Diabetes. 1995;44(Suppl 1):130A.

Page 10: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Summary of availableinsulin preparations

Agent Type / Administration

Glucose lowering

Basal Post-meal

NPH Intermediate-acting humanOnce or twice daily at bedtime ± breakfast

Detemir Long-acting analogueOnce or twice daily at bedtime ± breakfast

Glargine Long-acting analogueOnce daily at bedtime or before breakfast

Premixed Human or analogue mixTwice daily before breakfast and dinner

Regular Fast-acting humanBefore meals

Aspart, glulisine, lispro

Rapid-acting analogueBefore meals

Inhaled insulin Rapid-acting humanBefore meals

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Insulin Pens

• NovoMix®3030% insulin aspart in a soluble fraction and 70% insulin aspart crystallised with protamine

• NovoRapid®

Insulin aspart

• Insulatard®

NPH

Page 12: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

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

Monitoring

HCP Self Management Automation

Insulin & syringes

Pumps

Pens

Connectivity

Clinic Monitoring

Home Monitors

Data ManagementAdvice/Feedback

Open Loop

Delivery

Closed Loop

We are here!

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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

1. 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 The ADA Treatment Algorithm for the Initiation Algorithm for the Initiation

and Adjustment of Insulinand Adjustment of Insulin

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Normal physiologic patterns of glucose and insulin secretion in our body

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Page 21: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

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.

Page 22: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Initiating and Adjusting InsulinInitiating and Adjusting Insulin

Continue regimen; check HbA1c every 3 months

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)

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

If HbA1c ≤7%...

Bedtime intermediate-acting insulin, or bedtime or morning long-acting insulin

(initiate with 10 units or 0.2 units per kg)

Check FG and increase dose until in target range.

If HbA1c 7%...

Hypoglycemia or FG >3.89 mmol/l (70 mg/dl):

Reduce bedtime dose by ≥4 units(or 10% if dose >60 units)

Pre-lunch BG out of range: add rapid-acting insulin at breakfast

Pre-dinner BG out of range: add NPH insulin at breakfast or rapid-acting insulin at lunch

Pre-bed BG out of range: add rapid-acting insulin at dinner

Continue regimen; check HbA1c every 3 months

Target range: 3.89-7.22 mmol/L (70-130 mg/dL)

Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.

If HbA1c ≤7%... If HbA1c 7%...

Page 23: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Step One…

Continue regimen; check HbA1c every 3 months

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)

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

If HbA1c ≤7%...

Bedtime intermediate-acting insulin, or bedtime or morning long-acting insulin

(initiate with 10 units or 0.2 units per kg)

Check FG and increase dose until in target range.

If HbA1c 7%...

Hypoglycemia

or FG >3.89 mmol/l (70 mg/dl): Reduce bedtime dose by ≥4 units

(or 10% if dose >60 units)

Pre-lunch BG out of range: add rapid-acting insulin at breakfast

Pre-dinner BG out of range: add NPH insulin at breakfast or rapid-acting insulin at lunch

Pre-bed BG out of range: add rapid-acting insulin at dinner

Continue regimen; check HbA1c every 3 months

Target range: 3.89-7.22 mmol/L (70-130 mg/dL)

If HbA1c ≤7%... If HbA1c 7%...

Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.

Page 24: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Step One: Initiating InsulinStep 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 2006;29(8):1963-72.

Page 25: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Step One: Initiating InsulinStep One: Initiating Insulin, cont’d, cont’d

• 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 >10 mmol/l (>180 mg/dl), can increase by large increments (e.g., 4 units every 3 days)

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

Page 26: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

• If hypoglycemia occurs or if fasting glucose < 3.89 mmol/l (70 mg/dl)…– Reduce bedtime dose by ≥4 units or 10%

if dose >60 units

Step One: Initiating InsulinStep One: Initiating Insulin, cont’d, cont’d

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

Reduction in overnight and fasting glucose levels achieved by adding basal insulin may be sufficient to reduce postprandial elevations in glucose during the day and facilitate the achievement of target A1C concentrations.

While using basal insulin alone,never stop or reduce ongoing oral therapy

Page 27: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

• If HbA1c is <7%...

– Continue regimen and check HbA1c every 3 months

• If HbA1c is ≥7%...

– Move to Step Two…

After 2-3 Months…After 2-3 Months…

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

Page 28: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

With the addition of basal insulin and titration to target FBG levels, only about 60% of patients with type 2 diabetes are able to achieve A1C goals < 7%. In the remaining patients with A1C levels above goal regardless of adequate fasting glucose levels, postprandial blood glucose levels are likely elevated.

Page 29: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Continue regimen; check HbA1c every 3 months

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)

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

If HbA1c ≤7%...

Bedtime intermediate-acting insulin, or bedtime or morning long-acting insulin

(initiate with 10 units or 0.2 units per kg)

Check FG and increase dose until in target range.

If HbA1c 7%...

Hypoglycemia or FG >3.89 mmol/l (70 mg/dl):

Reduce bedtime dose by ≥4 units(or 10% if dose >60 units)

Pre-lunch BG out of range: add rapid-acting insulin at breakfast

Pre-dinner BG out of range: add NPH insulin at breakfast or rapid-acting insulin at lunch

Pre-bed BG out of range: add rapid-acting insulin at dinner

Continue regimen; check HbA1c every 3 months

Target range: 3.89-7.22 mmol/L (70-130 mg/dL)

If HbA1c ≤7%... If HbA1c 7%...

Step Two…

Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.

Page 30: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Step Two: Intensifying InsulinStep Two: Intensifying InsulinIf 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 2006;29(8):1963-72.

Page 31: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Making AdjustmentsMaking Adjustments

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

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

When number of insulin Injections increase from 1-2………..Stop or taper of insulin secretagogues (sulfonylureas).

Page 32: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

• If HbA1c is <7%...

– Continue regimen and check HbA1c every 3 months

• If HbA1c is ≥7%...

– Move to Step Three…

After 2-3 Months…After 2-3 Months…

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

Page 33: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.

Continue regimen; check HbA1c every 3 months

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)

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

If HbA1c ≤7%...

Bedtime intermediate-acting insulin, or bedtime or morning long-acting insulin

(initiate with 10 units or 0.2 units per kg)

Check FG and increase dose until in target range.

If HbA1c 7%...

Hypoglycemia or FG >3.89 mmol/l (70 mg/dl):

Reduce bedtime dose by ≥4 units(or 10% if dose >60 units)

Pre-lunch BG out of range: add rapid-acting insulin at breakfast

Pre-dinner BG out of range: add NPH insulin at breakfast or rapid-acting insulin at lunch

Pre-bed BG out of range: add rapid-acting insulin at dinner

Continue regimen; check HbA1c every 3 months

Target range: 3.89-7.22 mmol/L (70-130 mg/dL)

If HbA1c ≤7%... If HbA1c 7%...

Step Three…

Page 34: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Step Three: Step Three: Further Intensifying InsulinFurther 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 2006;29(8):1963-72.

Page 35: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Premixed InsulinPremixed 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 2006;29(8):1963-72.

Page 36: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Key Take-Home MessagesKey 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

Page 37: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Key Take-Home Messages, cont’dKey Take-Home Messages, cont’d

• 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.

Page 38: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Control random sugar level Control random sugar level by adjusting the prior dose by adjusting the prior dose

of regular insulinof regular insulin

Page 39: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Monitoring

1. Fasting hyperglycemia: - Check NPH bedtime dose

- Down Phenomenon

- Somogyi Effect

Use Regular before dinner and NPH at bedtime

Page 40: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Somogyi phenomenon

• Due to– excess dose of night time insulin, or– Night insulin taken early

• Peaks at 3:00 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 11:00 p.m so peak comes later– Reduce dose of night time insulin

Page 41: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

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

Page 42: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Monitoring, cont’d

2. Midmorning hyperglycemia: - Check fasting blood glucose

3. Sick day management: Do not reduce insulin dose

Page 43: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

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.

Page 44: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

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; 13:677.

• Swinnen SG, Hoekstra JB, DeVries JH. Diabetes Care. 2009 Nov;32 Suppl 2:S253-9. Diabetes Care. 2009;32 (Suppl 2):S253-9.

• Roach P. New insulin analogues and routes of delivery: pharmacodynamic and clinical considerations. Clin

Pharmacokinet. 2008;47:595-610.

• http://www.novonordisk.com/diabetes/public/insulinpens/flexpen/default.asp

Page 45: Insulin therapy Niloufar Ansari, Pharm. D. South Tehran Health Center, Tehran University of Medical Sciences.

Thank you all For Sparing your valuable time

&

Patient listening

Abr jungle, Shahroud, Iran