Post on 26-Dec-2015
Insulin therapy
Niloufar Ansari, Pharm. D.
South Tehran Health Center, Tehran University of Medical Sciences
The breakthrough: Toronto 1921 – Banting & Best
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
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
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.
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.
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)
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.
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
Insulin Pens
• NovoMix®3030% insulin aspart in a soluble fraction and 70% insulin aspart crystallised with protamine
• NovoRapid®
Insulin aspart
• Insulatard®
NPH
Insulin Pens
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)
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!
Injection Techniques
Sites of injection
• Arms • Legs • Buttocks
• Abdomen • Easy access
• Ample subcutaneous tissue
• Absorption is not affected by exercise.
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
The ADA Treatment The ADA Treatment Algorithm for the Initiation Algorithm for the Initiation
and Adjustment of Insulinand Adjustment of Insulin
Normal physiologic patterns of glucose and insulin secretion in our body
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.
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%...
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.
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.
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.
• 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
• 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.
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.
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.
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.
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).
• 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.
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…
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.
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.
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
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.
Control random sugar level Control random sugar level by adjusting the prior dose by adjusting the prior dose
of regular insulinof regular insulin
Monitoring
1. Fasting hyperglycemia: - Check NPH bedtime dose
- Down Phenomenon
- Somogyi Effect
Use Regular before dinner and NPH at bedtime
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
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
Monitoring, cont’d
2. Midmorning hyperglycemia: - Check fasting blood glucose
3. Sick day management: Do not reduce insulin dose
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.
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
Thank you all For Sparing your valuable time
&
Patient listening
Abr jungle, Shahroud, Iran