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The Community Pharmacist’s Role in
Diabetes Management

2

Overview of Insulin
Products:
New Developments Review

Anas Bahnassi PhD RPh
This boy was
Leonard Thompson

Without insulin, this young
girl would have died in a
matter of days or weeks.

2
11/15/2013

Overview of insulin products - CE for Pharmacists

On January 11, 1922, at 14
years of age, A Canadian
boy from Toronto received
his first shot of insulin.
Patient is
diagnosed
with type
one
diabetes

Full day “conventional” coverage
Premixed insulin twice daily
Custom designed split mix variant

Full physiologic insulin coverage
Long acting analog at bedtime and
Rapid acting before meals

3
11/15/2013

Overview of insulin products - CE for Pharmacists

Possible Insulin Treatments
in Type-1 Diabetes:
Insulin use in type-2 diabetes

Overview of insulin products - CE for Pharmacists

• Start insulin if severe symptoms at time of diagnosis
or present with DKA.
• Pregnancy.
• Add insulin when antidiabetes medictions fail:
– Basal insulin is more cost effective than a
third oral agent.
– Insulin added to suboptimally controlled
patients on 2 oral antidiabetes medications
will result in A1C lowering by 1.5%.

4
11/15/2013
Type-2 diabetes evolving treatment
paradigm
-5

0

+5

+10
Amylin
Pramlintide

Diagnosis
Inhaled Insulin

Overview of insulin products - CE for Pharmacists

Years since diagnosis

-10

Insulin

Onset
GLP-1 Analogs and DPP-4
Inhibitors
Oral combotherapy
Oral
monotherapy

Diet and exercise
Pre-diabetes

Type-2 diabetes
5

11/15/2013
Percentage of patients advancing
when A1C >8%
66.6

When insulin was started, the average patient had:
• 5 years of A1C >8%
• 10 years of A1C >7%
44.6
35.5

18.8

Diet

Sulfonylurea

Metformin

Combination
6

11/15/2013

Overview of insulin products - CE for Pharmacists

Percentage

Brown JB et al. Diabetes Care (2004)
Barriers to insulin use
Physician resistance:

Compliance issues
Fears of scars
Administration difficulties

Lack of resources.
Time to plan and followup intensive therapy.

Perceived and real ADRs:
Weight gain, hypoglycemia

Optimal glycemic control requires
multiple daily injections.
7
11/15/2013

Overview of insulin products - CE for Pharmacists

Patient resistance:
Barriers to insulin use
All patients

High anxiety patients

Overview of insulin products - CE for Pharmacists

63

44

42

35

18

0
Troubled by the
idea of multiple
shots
11/15/2013

Avoid injection
due to anxiety

High anxiety
about injections
8

Zambanini A et al. Diabetes Res. Clin. Pract.(1999)
• Set appropriate goals
• Patient education
• Prudent assistance by others
• Use of premixed insulin
• Physiologic insulin treatment design
• Balance of food, activity, and insulin
• Injection devices

9
11/15/2013

Overview of insulin products - CE for Pharmacists

Overcoming patient obstacles
Physical and Chemical Properties
of Human Insulin
21 amino acids

α-chain
β-chain

Overview of insulin products - CE for Pharmacists

30 amino acids

Monomers

Dimers

Zn++
Zn++

Self-aggregation
in solution

Hexamers
(around Zn2+)
10

11/15/2013
The best insulin type for your
patient’s diabetes

•
•
•
•
•
•

Overview of insulin products - CE for Pharmacists

The best type of insulin for your patient
depends on many factors:
Individualized response to insulin
Lifestyle choices
Willing to use multiple injections daily
Frequency of glucose checking
Age
Blood glucose management goals
11
11/15/2013
Types of insulin
Rapid acting
Short acting
Intermediate acting
Long acting
Premixed

Overview of insulin products - CE for Pharmacists

•
•
•
•
•

12
11/15/2013
Rapid acting insulin
Duration Role in glucose
Brand
management
hr
Rapid-acting
Humalog or
15-30 30-90 3-5
insulin covers
lispro
insulin needs for
Novolog or
10-20 40-50 3-5
meals eaten at
aspart
the same time
as the injection.
This type of
Apidra or
insulin is often
20-30 30-90 1-2½
glulisine
used with
longer-acting
insulin.
13

11/15/2013

Overview of insulin products - CE for Pharmacists

Onset Peak
min min
Lispro

Gly

Glu

Phe

Tyr

Thr

23

Insulin

24

25

26

27

Gly

Glu

Phe

Tyr

Thr

Pro
28
Lys

Lys
29
Pro

Overview of insulin products - CE for Pharmacists

Primary Structure of
Lys(B28), Pro(B29)–Insulin

Thr
30
Thr

14
11/15/2013
Aspart

Gly

Glu

Phe

23

Insulin

24

25

Gly

Glu

Phe

Tyr
26
Tyr

Thr
27
Thr

Pro
28
Asp

Lys
29
Lys

Overview of insulin products - CE for Pharmacists

Primary Structure of
Asp(B28)-Insulin

Thr
30
Thr

15
11/15/2013
Insulin

Phe
1

Glulisine

Phe

Val
2
Val

Asn

Gln

Pro

Lys

Thr

3

4

28

29

30

Lys

Gln

Pro

Glu

Overview of insulin products - CE for Pharmacists

Primary Structure of
Glu(B29), Lisine(B3)–Insulin

Thr

16
11/15/2013
Heinmann et al. Diabet. Med. 1996

Lys Pro

Asp

Lys

11/15/2013

Glu

Overview of insulin products
- CE for Pharmacists

17
Brand

Onset Peak
min hr

Regular (R)
humulin or 30-60 2-5
novolin
Velosulin
(for use in
30-60 2-3
the insulin
pump)

Duration Role in glucose
management
hr
Short-acting
5-8
insulin covers
insulin needs for
meals eaten
within 30-60
2-3
minutes

18
11/15/2013

Overview of insulin products - CE for Pharmacists

Short acting insulin
Intermediate acting insulin

NPH (N)

19

11/15/2013

Overview of insulin products - CE for Pharmacists

Brand

Duration Role in glucose
management
hr
Intermediateacting insulin
covers insulin
needs for about
half the day or
1-2
4-12 18-24
overnight. This
hours hours hours
type of insulin is
often combined
with rapid- or
short-acting
insulin

Onset Peak
min hr
Overview of insulin products - CE for Pharmacists

Action Profiles of Injected Human
Insulins

Plasma insulin levels

Regular 6–8 hours

NPH 12–20 hours

0

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Hours
11/15/2013

20
Brand

Lantus
(insulin
glargine)

11/15/2013

Levemir
(insulin
detemir)

Duration Role in glucose
management
hr
Long-acting
insulin covers
insulin needs for
about one full
20-24
day. This type of
hours
insulin is often
combined, when
needed, with
rapid- or shortacting insulin
1-2
6-8
Up to 24
hours hours hours
21

Onset Peak
min hr
No
peak
time;
insulin
1-1½
is
hour
deliver
ed at a
steady
level

Overview of insulin products - CE for Pharmacists

Long acting insulin
Primary Structure of Gly(A21),
Arg(B31), Arg(B32)-Insulin
Leu

Glu

Asn

Tyr

Cys

Asn

16

17

18

19

20

21

Glargine

Leu

Glu

Asn

Tyr

Cys

Gly

Insulin
B-chain

Phe Tyr

Thr

Pro

Lys

Thr

25

26

27

28

29

Glargine

Phe Tyr

Thr

Pro

Lys

Overview of insulin products - CE for Pharmacists

Insulin
A-chain

30

Thr

Arg

Arg
22

11/15/2013
Primary Structure of Lys(B29)-N-Tetradecanoyl, Des(B30)-Insulin
Glu

Phe

Tyr

Thr

24

25

26

27

Gly

Glu

Phe

Tyr

Thr

Pro
28

Pro

Lys
29

Thr
30

Lys

Thr

(CH2)4

11/15/2013

• Fatty acid tail (myristic acid) added
to human insulin
• Complexes with albumin>20 hour
action

NH
CO

R

23

Overview of insulin products - CE for Pharmacists

Detemir

Gly
23

Insulin
Glucose infusion rates
(mg/kg/min)

6

NPH

5
4

Glargine

0.4 U/kg

3
2

Placebo

1
0
0

2

4

6

8

10 12 14 16 18 20 22 24 26 28 30
Time (h)

24
11/15/2013

Linkeschowa R, et al. Diabetes.1999;48(suppl 1):A97.

Overview of insulin products - CE for Pharmacists

Action Profiles of long acting
insulin analogs – Glargine
Action Profiles of long acting
insulin analogs – Detemir

1.5
1.0

Detemir - high
Detemir - low

0.5
Placebo
0.0
-100

100

300

500

700

900

1100

1300

1500

Overview of insulin products - CE for Pharmacists

Glucose infusion rate
(mg/kg/min)

2.0

Elapsed time (min)
25
11/15/2013

Brunner GA, et al. Exp Clin Endocrinol Diabetes. 2000;108:100-105.
Brand

Onset Peak
min hr

Humulin
70/30

30

2-4

Novolin
70/30

30

2-12

Novolog
70/30

10-20 1-4

Duration Role in glucose
management
hr
These products
14-24
are generally
taken two or
Up to 24 three times a
day before
mealtime.
Up to 24

26
11/15/2013

Overview of insulin products - CE for Pharmacists

Premixed insulin
Mixed vs. Basal Insulin Regimens
Analog mix
vs.
Human mix

Analog mix
vs. Long-acting
analogs

Analog mix
vs. “Other
regimens”

Strength of
Evidence

FPG

Similar

Favors longacting analog

Unknown

Moderate

PPG

Favors
analog mix

Favors analog
mix

Unknown

High

A1c Reduction

Similar

Favors analog
mix

Unknown

High

Hypoglycemia

Similar

Favors longacting analog

Unknown

High

Weight

Similar

Favors longacting analog

Unknown

Moderate

Mortality

Unknown

Unknown

Unknown

Unknown

Overview of insulin products - CE for Pharmacists

Outcome

27

11/15/2013

Qayyum R et al, Ann Intern Med 2008;149:549-559
• Determine who needs insulin
initiation
• Design a system that includes
the type of insulin that fits your
patient’s lifestyle
• Be ready to explain the
differences between types of
insulin
28
11/15/2013

Overview of insulin products - CE for Pharmacists

Sum-up
The Community Pharmacist’s Role in Diabetes Management
CE program for pharmacists

Anas Bahnassi PhD CDM CDE
abahnassi@gmail.com

http://www.twitter.com/abpharm

http://www.facebook.com/pharmaprof

http://www.linkedin.com/in/abahnassi

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A quick review of available insulin products

  • 1. The Community Pharmacist’s Role in Diabetes Management 2 Overview of Insulin Products: New Developments Review Anas Bahnassi PhD RPh
  • 2. This boy was Leonard Thompson Without insulin, this young girl would have died in a matter of days or weeks. 2 11/15/2013 Overview of insulin products - CE for Pharmacists On January 11, 1922, at 14 years of age, A Canadian boy from Toronto received his first shot of insulin.
  • 3. Patient is diagnosed with type one diabetes Full day “conventional” coverage Premixed insulin twice daily Custom designed split mix variant Full physiologic insulin coverage Long acting analog at bedtime and Rapid acting before meals 3 11/15/2013 Overview of insulin products - CE for Pharmacists Possible Insulin Treatments in Type-1 Diabetes:
  • 4. Insulin use in type-2 diabetes Overview of insulin products - CE for Pharmacists • Start insulin if severe symptoms at time of diagnosis or present with DKA. • Pregnancy. • Add insulin when antidiabetes medictions fail: – Basal insulin is more cost effective than a third oral agent. – Insulin added to suboptimally controlled patients on 2 oral antidiabetes medications will result in A1C lowering by 1.5%. 4 11/15/2013
  • 5. Type-2 diabetes evolving treatment paradigm -5 0 +5 +10 Amylin Pramlintide Diagnosis Inhaled Insulin Overview of insulin products - CE for Pharmacists Years since diagnosis -10 Insulin Onset GLP-1 Analogs and DPP-4 Inhibitors Oral combotherapy Oral monotherapy Diet and exercise Pre-diabetes Type-2 diabetes 5 11/15/2013
  • 6. Percentage of patients advancing when A1C >8% 66.6 When insulin was started, the average patient had: • 5 years of A1C >8% • 10 years of A1C >7% 44.6 35.5 18.8 Diet Sulfonylurea Metformin Combination 6 11/15/2013 Overview of insulin products - CE for Pharmacists Percentage Brown JB et al. Diabetes Care (2004)
  • 7. Barriers to insulin use Physician resistance: Compliance issues Fears of scars Administration difficulties Lack of resources. Time to plan and followup intensive therapy. Perceived and real ADRs: Weight gain, hypoglycemia Optimal glycemic control requires multiple daily injections. 7 11/15/2013 Overview of insulin products - CE for Pharmacists Patient resistance:
  • 8. Barriers to insulin use All patients High anxiety patients Overview of insulin products - CE for Pharmacists 63 44 42 35 18 0 Troubled by the idea of multiple shots 11/15/2013 Avoid injection due to anxiety High anxiety about injections 8 Zambanini A et al. Diabetes Res. Clin. Pract.(1999)
  • 9. • Set appropriate goals • Patient education • Prudent assistance by others • Use of premixed insulin • Physiologic insulin treatment design • Balance of food, activity, and insulin • Injection devices 9 11/15/2013 Overview of insulin products - CE for Pharmacists Overcoming patient obstacles
  • 10. Physical and Chemical Properties of Human Insulin 21 amino acids α-chain β-chain Overview of insulin products - CE for Pharmacists 30 amino acids Monomers Dimers Zn++ Zn++ Self-aggregation in solution Hexamers (around Zn2+) 10 11/15/2013
  • 11. The best insulin type for your patient’s diabetes • • • • • • Overview of insulin products - CE for Pharmacists The best type of insulin for your patient depends on many factors: Individualized response to insulin Lifestyle choices Willing to use multiple injections daily Frequency of glucose checking Age Blood glucose management goals 11 11/15/2013
  • 12. Types of insulin Rapid acting Short acting Intermediate acting Long acting Premixed Overview of insulin products - CE for Pharmacists • • • • • 12 11/15/2013
  • 13. Rapid acting insulin Duration Role in glucose Brand management hr Rapid-acting Humalog or 15-30 30-90 3-5 insulin covers lispro insulin needs for Novolog or 10-20 40-50 3-5 meals eaten at aspart the same time as the injection. This type of Apidra or insulin is often 20-30 30-90 1-2½ glulisine used with longer-acting insulin. 13 11/15/2013 Overview of insulin products - CE for Pharmacists Onset Peak min min
  • 14. Lispro Gly Glu Phe Tyr Thr 23 Insulin 24 25 26 27 Gly Glu Phe Tyr Thr Pro 28 Lys Lys 29 Pro Overview of insulin products - CE for Pharmacists Primary Structure of Lys(B28), Pro(B29)–Insulin Thr 30 Thr 14 11/15/2013
  • 15. Aspart Gly Glu Phe 23 Insulin 24 25 Gly Glu Phe Tyr 26 Tyr Thr 27 Thr Pro 28 Asp Lys 29 Lys Overview of insulin products - CE for Pharmacists Primary Structure of Asp(B28)-Insulin Thr 30 Thr 15 11/15/2013
  • 16. Insulin Phe 1 Glulisine Phe Val 2 Val Asn Gln Pro Lys Thr 3 4 28 29 30 Lys Gln Pro Glu Overview of insulin products - CE for Pharmacists Primary Structure of Glu(B29), Lisine(B3)–Insulin Thr 16 11/15/2013
  • 17. Heinmann et al. Diabet. Med. 1996 Lys Pro Asp Lys 11/15/2013 Glu Overview of insulin products - CE for Pharmacists 17
  • 18. Brand Onset Peak min hr Regular (R) humulin or 30-60 2-5 novolin Velosulin (for use in 30-60 2-3 the insulin pump) Duration Role in glucose management hr Short-acting 5-8 insulin covers insulin needs for meals eaten within 30-60 2-3 minutes 18 11/15/2013 Overview of insulin products - CE for Pharmacists Short acting insulin
  • 19. Intermediate acting insulin NPH (N) 19 11/15/2013 Overview of insulin products - CE for Pharmacists Brand Duration Role in glucose management hr Intermediateacting insulin covers insulin needs for about half the day or 1-2 4-12 18-24 overnight. This hours hours hours type of insulin is often combined with rapid- or short-acting insulin Onset Peak min hr
  • 20. Overview of insulin products - CE for Pharmacists Action Profiles of Injected Human Insulins Plasma insulin levels Regular 6–8 hours NPH 12–20 hours 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Hours 11/15/2013 20
  • 21. Brand Lantus (insulin glargine) 11/15/2013 Levemir (insulin detemir) Duration Role in glucose management hr Long-acting insulin covers insulin needs for about one full 20-24 day. This type of hours insulin is often combined, when needed, with rapid- or shortacting insulin 1-2 6-8 Up to 24 hours hours hours 21 Onset Peak min hr No peak time; insulin 1-1½ is hour deliver ed at a steady level Overview of insulin products - CE for Pharmacists Long acting insulin
  • 22. Primary Structure of Gly(A21), Arg(B31), Arg(B32)-Insulin Leu Glu Asn Tyr Cys Asn 16 17 18 19 20 21 Glargine Leu Glu Asn Tyr Cys Gly Insulin B-chain Phe Tyr Thr Pro Lys Thr 25 26 27 28 29 Glargine Phe Tyr Thr Pro Lys Overview of insulin products - CE for Pharmacists Insulin A-chain 30 Thr Arg Arg 22 11/15/2013
  • 23. Primary Structure of Lys(B29)-N-Tetradecanoyl, Des(B30)-Insulin Glu Phe Tyr Thr 24 25 26 27 Gly Glu Phe Tyr Thr Pro 28 Pro Lys 29 Thr 30 Lys Thr (CH2)4 11/15/2013 • Fatty acid tail (myristic acid) added to human insulin • Complexes with albumin>20 hour action NH CO R 23 Overview of insulin products - CE for Pharmacists Detemir Gly 23 Insulin
  • 24. Glucose infusion rates (mg/kg/min) 6 NPH 5 4 Glargine 0.4 U/kg 3 2 Placebo 1 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 Time (h) 24 11/15/2013 Linkeschowa R, et al. Diabetes.1999;48(suppl 1):A97. Overview of insulin products - CE for Pharmacists Action Profiles of long acting insulin analogs – Glargine
  • 25. Action Profiles of long acting insulin analogs – Detemir 1.5 1.0 Detemir - high Detemir - low 0.5 Placebo 0.0 -100 100 300 500 700 900 1100 1300 1500 Overview of insulin products - CE for Pharmacists Glucose infusion rate (mg/kg/min) 2.0 Elapsed time (min) 25 11/15/2013 Brunner GA, et al. Exp Clin Endocrinol Diabetes. 2000;108:100-105.
  • 26. Brand Onset Peak min hr Humulin 70/30 30 2-4 Novolin 70/30 30 2-12 Novolog 70/30 10-20 1-4 Duration Role in glucose management hr These products 14-24 are generally taken two or Up to 24 three times a day before mealtime. Up to 24 26 11/15/2013 Overview of insulin products - CE for Pharmacists Premixed insulin
  • 27. Mixed vs. Basal Insulin Regimens Analog mix vs. Human mix Analog mix vs. Long-acting analogs Analog mix vs. “Other regimens” Strength of Evidence FPG Similar Favors longacting analog Unknown Moderate PPG Favors analog mix Favors analog mix Unknown High A1c Reduction Similar Favors analog mix Unknown High Hypoglycemia Similar Favors longacting analog Unknown High Weight Similar Favors longacting analog Unknown Moderate Mortality Unknown Unknown Unknown Unknown Overview of insulin products - CE for Pharmacists Outcome 27 11/15/2013 Qayyum R et al, Ann Intern Med 2008;149:549-559
  • 28. • Determine who needs insulin initiation • Design a system that includes the type of insulin that fits your patient’s lifestyle • Be ready to explain the differences between types of insulin 28 11/15/2013 Overview of insulin products - CE for Pharmacists Sum-up
  • 29. The Community Pharmacist’s Role in Diabetes Management CE program for pharmacists Anas Bahnassi PhD CDM CDE abahnassi@gmail.com http://www.twitter.com/abpharm http://www.facebook.com/pharmaprof http://www.linkedin.com/in/abahnassi