Overview of Insulin Products: New Developments Review

Anas Bahnassi PhD RPh

The Community Pharmacist’s Role in Diabetes Management 2

On January 11, 1922, at 14 years of age, A Canadian boy from Toronto received his first shot of insulin. This boy was Leonard Thompson

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

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Possible Insulin Treatments in Type-1 Diabetes:

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

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Insulin use in type-2 diabetes

• 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%.

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Type-2 diabetes evolving treatment paradigm

Pre-diabetes Type-2 diabetes

Diet and exercise

Oral monotherapy

Oral combotherapy

GLP-1 Analogs and DPP-4 Inhibitors

Insulin Inhaled Insulin

Amylin Pramlintide

0 -5 -10 +10 +5

Onset

Diagnosis

Year

s si

nce

dia

gno

sis

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Percentage of patients advancing when A1C >8%

Diet Sulfonylurea Metformin Combination

66.6

35.5

44.6

18.8

Percentage

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

Brown JB et al. Diabetes Care (2004) 11/15/2013

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Barriers to insulin use

Patient resistance: Compliance issues Fears of scars Administration difficulties

Physician resistance: Lack of resources. Time to plan and follow-up intensive therapy.

Perceived and real ADRs: Weight gain, hypoglycemia

Optimal glycemic control requires multiple daily injections.

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Barriers to insulin use

Troubled by the idea of multiple

shots

Avoid injection due to anxiety

High anxiety about injections

42

18

35

63

44

0

All patients High anxiety patients

Zambanini A et al. Diabetes Res. Clin. Pract.(1999) 11/15/2013

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Overcoming patient obstacles

• 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

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Physical and Chemical Properties of Human Insulin

α-chain

β-chain

Zn++

Zn++

Self-aggregation in solution

Monomers

Dimers

Hexamers

(around Zn2+)

21 amino acids

30 amino acids

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The best insulin type for your patient’s diabetes

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

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Types of insulin

• Rapid acting

• Short acting

• Intermediate acting

• Long acting

• Premixed

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Rapid acting insulin

Brand Onset min

Peak min

Duration hr

Role in glucose management

Humalog or lispro

15-30 30-90 3-5 Rapid-acting insulin covers insulin needs for meals eaten at the same time as the injection. This type of insulin is often used with longer-acting insulin.

Novolog or aspart

10-20 40-50 3-5

Apidra or glulisine

20-30 30-90 1-2½

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Gly Thr Glu Phe Tyr Pro Lys Thr

Gly Thr Glu Phe Tyr Lys Pro Thr

23 24 25 26 27 28 29 30

Insulin

Lispro

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

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Gly Thr Glu Phe Tyr Pro Lys Thr

Gly Thr Glu Phe Tyr Asp Lys Thr

23 24 25 26 27 28 29 30

Insulin

Aspart

Primary Structure of Asp(B28)-Insulin

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Phe Val Asn Gln Pro Lys Thr

Phe Val Lys Gln Pro Glu Thr

1 2 3 4 28 29 30

Insulin

Glulisine

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

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Asp

Lys Pro

Lys Glu

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17 Overview of insulin products - CE for Pharmacists

Hei

nm

ann

et

al. D

iab

et. M

ed. 1

99

6

Short acting insulin

Brand Onset min

Peak hr

Duration hr

Role in glucose management

Regular (R) humulin or novolin

30-60 2-5 5-8 Short-acting insulin covers insulin needs for meals eaten within 30-60 minutes

Velosulin (for use in the insulin pump)

30-60 2-3 2-3

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Intermediate acting insulin

Brand Onset min

Peak hr

Duration hr

Role in glucose management

NPH (N) 1-2 hours

4-12 hours

18-24 hours

Intermediate-acting insulin covers insulin needs for about half the day or overnight. This type of insulin is often combined with rapid- or short-acting insulin

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Action Profiles of Injected Human Insulins

0 1 2 5 3 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Pla

sma

insu

lin le

vels

Regular 6–8 hours

NPH 12–20 hours

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Long acting insulin

Brand Onset min

Peak hr

Duration hr

Role in glucose management

Lantus (insulin glargine)

1-1½ hour

No peak time; insulin is delivered at a steady level

20-24 hours

Long-acting insulin covers insulin needs for about one full day. This type of insulin is often combined, when needed, with rapid- or short-acting insulin Levemir

(insulin detemir)

1-2 hours

6-8 hours

Up to 24 hours

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Thr Phe Tyr Pro Lys Thr

25 26 27 28 29 30

Insulin B-chain

Glargine Thr Phe Tyr Pro Lys Thr Arg Arg

Asn Leu Glu Tyr Cys Gly

Asn Leu Glu Tyr Cys Asn

16 17 18 19 20 21

Insulin A-chain

Glargine

Primary Structure of Gly(A21), Arg(B31), Arg(B32)-Insulin

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Gly Thr Glu Phe Tyr Pro Lys Thr

Gly Thr Glu Phe Tyr Pro Lys Thr

23 24 25 26 27 28 29 30

Insulin

Detemir

(CH2)4

NH

CO

R

Primary Structure of Lys(B29)-N--Tetradecanoyl, Des(B30)-Insulin

• Fatty acid tail (myristic acid) added to human insulin

• Complexes with albumin>20 hour action

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

Action Profiles of long acting insulin analogs – Glargine

0

0

1

2

3

4

5

6

2 4 6 8 10 12 14 16 18 20 22 24 26 28 30

NPH

Glargine

Placebo

0.4 U/kg

Time (h)

Glu

cose

infu

sio

n r

ates

(m

g/k

g/m

in)

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Action Profiles of long acting insulin analogs – Detemir

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

Elapsed time (min)

0.0

0.5

1.0

1.5

2.0

-100 100 300 500 700 900 1100 1300 1500

Detemir - high

Detemir - low

Placebo

Glu

cose

infu

sio

n r

ate

(m

g/k

g/m

in)

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Premixed insulin

Brand Onset min

Peak hr

Duration hr

Role in glucose management

Humulin 70/30

30 2-4 14-24 These products are generally taken two or three times a day before mealtime.

Novolin 70/30

30 2-12 Up to 24

Novolog 70/30

10-20 1-4 Up to 24

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Mixed vs. Basal Insulin Regimens

Outcome Analog mix vs. Human mix

Analog mix vs. Long-acting analogs

Analog mix vs. “Other regimens”

Strength of Evidence

FPG Similar Favors long-acting analog

Unknown Moderate

PPG Favors analog mix

Favors analog mix

Unknown High

A1c Reduction Similar Favors analog mix

Unknown High

Hypoglycemia Similar Favors long-acting analog

Unknown High

Weight Similar Favors long-acting analog

Unknown Moderate

Mortality Unknown Unknown Unknown Unknown

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Qayyum R et al, Ann Intern Med 2008;149:549-559

Sum-up

• 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

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

abahnassi@gmail.com

http://www.twitter.com/abpharm

http://www.facebook.com/pharmaprof

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

Anas Bahnassi PhD CDM CDE