Insulin Preparations

What is insulin?

 Isa hormone secreted by the

pancreatic beta cells that facilitates
the uptake of glucose into skeletal
muscle and adipose tissue by
increasing the number of glucose
transporters ( GLUT 1 and GLUT 4)
that facilitate glucose diffusion into
these targeted cells.
 What is insulin

 A protein that contains 51 amino acids

 When the supply of, or response to, insulin is
adequate, the disease is known as Type
1(IDDM or juvenile-onset) and Type 2
(NIDDM or adult onset) Diabetes
respectively.
 Insulin Injections

 Are
divided into 4 major categories
namely
 Rapid acting
 Short acting
 Intermediate Acting
 Long Acting
 Rapid Acting Insulin

 Insulin Aspart (Novolog)

 Same with the regular Human insulin except that
proline was replaced by Aspartic acid in position
B28
 Onset :15 min; duration: 2-4 hours
 Rapid Acting Insulin

 Insulin Lispro (Humalog)

 B28 Lys and B29 Proline Human insulin analog
where in the usual B28 Proline and B29 Lysine
is reversed
 Onset:15 mins;duration:2-4 hours
 Rapid Acting Insulin

 Insulin glulisine
 is another insulin analogue, with asparagine
at position B3 replaced by lysine, and lysine
at B29 replaced by glutamic acid
 Same with other rapid acting insulins
 Short Acting Insulins

 Regular Insulin (Humulin or Novolin)

 The only insulin that is approved to be
administered via IV route
 Comes from Pork(porcine), beef(bovine) or
Human pancreas or genetically engineered
using rDNA technology from certain
microorganisms(E.coli)
 Onset:30-60 min;duration:6 to 8 hours
 Intermediate Acting Insulin

 Isophane Insulin Suspension or Neutral

Protamine Hagedorn (NPH) (Humulin N and
Novolin N)
 A sterile suspension of Zinc Insulin crystals
and Protamine sulfate—a protein from the
sperm of a fish (Onchorynchus Fam.
Salmonidae)
 Onset:1 to 2 hours; duration:10 to 16 hours
 Intermediate Acting Insulin

 Insulin Zinc Suspension (Lente)

 A sterile suspension of insulin modified by the
addition of Zinc chloride
 It has an advantage of fewer allergic reactions
than NPH
 Onset:1 to 2 hours:duration:10 to 16 hours
 Long Acting Insulins

 Glargine (Lantus)
 Differs from Human insulin that asparagine
at position A21 is replaced by GLycine and
an additional 30B-a-L-ARGinine-30B-b-L-
arginINE
 A clear solution that is the only true 24-hour
insulin available
 Long Acting Insulins

 Glargine (Lantus)
 Onset:2 hours;duration:24 hours
 Long Acting Insulins

 Extended Insulin Zinc suspension(Ultra

Lente)
 A sterile suspension of insulin modified by
the addition of Zinc chloride
 Onset:4 to 8 hours:duration:36 hours
 Long Acting Insulins

 Insulin detemir is another long-acting

insulin analogue that may have some benefit
over isophane insulin.
 It is a neutral soluble human insulin
analogue in which the terminal amino acid at
B30 has been replaced by myristic acid, a
14-carbon fatty acid chain.
 Duration: up to 24 hours
 Insulin Combinations

 Pre-mixed
 Novolin 70/30-contains 70 % NPH and 30 %
Regular Insulin
 Humulin 50/50-contains 50 % NPH and 50%
Regular insulin
 Insulin Combinations

 Mixtures of insulin are being prepared prior

to administration if the pre-mixed
combinations of insulin are not suitable for
the patient or not available
 A combination of either a rapid or short
acting insulin and an intermediate or long
acting insulin is being used (except Insulin
Glargine which should not be used in
combination with any other types of insulin)
 Insulin Combinations

 Guidelines in mixing insulin prior to

administration
 If not specified in a doctor’s order, use insulin of
same concentration
 Use proper syringe to measure insulin in units or
mL
 Do not contaminate the contents of one vial with
the contents of another vial
 Insulin Combinations
 Always draw the short acting or regular insulin,
which is clear, first, then follow it with the
intermediate or long acting insulin (cloudy)
 Never mix a short acting insulin with a Lente or
Ultralente
 Never mix a phosphate-buffered insulin(isophane)
with a lente or Ultralente
 Insulin administration

 Almost always being administered via SC

route usually in the arm, thigh or abdomen
 Administered by using an insulin syringe or a
tuberculin syringe
 Can also be administered by a portable pen
injector, which contains a cartridge that
holds the insulin or a continuous
subcutaneous Insulin infusion (CSII)
device, commonly know as an insulin pump
Pre-filled (Disposable)

FlexPen®

SoloStar® (sanofi aventis)

Re-usable (uses insulin cartridges)

HumaPen ®

NovoPen® 4
Portable Pen Injector
Inhalation device for insulin
Continuous Subcutaneous
Insulin Infusion (CSII) Device
 Insulin administration
Sites
• Abdomen (fastest absorption & most
preferred)
• Buttocks (Intermed
iate)
• Upper arm
• Thigh-lateral & anterior aspects (slowest)
• Rotate the site of injection around a
selected area
 Types of insulin
Type of Insulin Onset Peak Duration Role in Blood Sugar
& Brand Names Management
Rapid-Acting
Lispro 15-30 min. 30-90 min 3-5 hoursCovers insulin needs for
meals eaten at the same
Aspart 10-20 min. 40-50 min. 3-5 hours
time as the injection.
Glulisine 20-30 min. 30-90 min. 1-2½ hours

Short-Acting
Regular 30 min- 60 2-5 hours 5-8 hours Covers insulin needs for
min meals eaten within 30-60
minutes
Intermediate-Acting
NPH (N) 1-2 hours 4-12 hours 18-24 hours Covers insulin needs for
about half the day or
overnight.
 Types of insulin
Name of Onset Duration Role in Blood
Insulin Sugar
Management
Long-Acting
Long-acting Degludec 30-90 min No peak: Longer than 24
insulin covers insulin is hours
insulin needs Glargine 30-90 min delivered at Up to 24 hours
for about one a steady
full day. Detemir 1-120 min level. 20-24 hours
 Types of insulin
Type of Insulin Onset Peak Duration Role in Blood Sugar
Management
Pre-Mixed*
30/70 30 min. 2-4 hours 14-24 hours These products are
generally taken two
50/50 30 min. 2-5 hours 18-24 hours or three times a day
before mealtime.
25/75 15 min. 30 min.-2½ 16-20 hours
hours
Inhaler
Exubera Banned
Afrezza With in min 12 to 15 min 2-3 hours Post prandial effects.

*Premixed insulins are a combination of specific proportions of intermediate-

acting and short-acting insulin in one bottle or insulin pen (the numbers the brand
name indicate the percentage of each type of insulin).
Injection Technique

© 2004 BD
Injection Technique

© 2004 BD
Injection Technique

© 2004 BD
Injection Technique

© 2004 BD
Injection Technique

© 2004 BD
Injection Technique
Injection Technique

© 2004 BD
 Sharps Disposal

Needles from syringes, pen devices and

lancets are classified as group B clinical
waste.

Sharps bins and safe clips are available on

prescription.

Disposal of sharps bin varies depending on

local policy.
 INSULIN
ANALOGUES
 CONTENTS
Introduction
Classification
Rationale for
development
Individual analogues
Special features
Merits of analogues over standard
insulins
Drawbacks of analogues
Popular regimes using analogues
Novel delivery systems using analogues
Summary
 INSULIN

The most powerful agent we have to control glucose.

Miracle discovery that saved many lives.
ANALOGUES……………
..
1921 : Insulin extracted by Banting &
Best.
Conventional insulin preparations from beef/pork pancreas
(antigenic)
1970s : Highly purified porcine insulins : Single peak
insulins &
Monocompetent insulins (greater efficacy & lesser side
effects)
1980s : Human insulins by recombinant DNA technology (still
better)
1990 : Insulin analogues with novel pharmacokinetics ( Eli Lilly&
Co.)
 SO……WHAT ARE INSULIN
ANALOGUES??

Molecules produced by genetic engineering wherein the amin

acid
sequence in human insulin is changed to alter its
pharmacokinetics.
However, they bind to insulin receptors in the same way as
human
insulin and produce similar effects

Also termed as: Designer Insulins

Insulin receptor
ligands
Democratic insulins
CLASSIFICATION
INSULIN
INSULINS
ANALOGUES
Ultra-short acting/Rapid acting
Short acting - Lispro
- Regular - Aspart
- Glulisine
Intermediate
acting Long acting
- NPH / Isophane - Glargine
- Detemir
Pre-mix insulins of
- Degludec
NPH/Regular
insulins
** Protaminated lispro – NPL
Protaminated Aspart – NPA
Pre mix analogues of NPL with Lispro (50/50
&75/25)
Pre mix analogues of NPA with Aspart
(70/30)
CLASSIFICATION

Insulin and analogue preparations

Short acting Long acting

- Regular - NPH
- Lispro - Glargine
- Aspart - Detemir
- Glulisine - Degludec
What was the need for insulin analogues when we
had improved insulins???
SO……………………………
….

Insulin analogues were developed to overcome the

limitations of
available
- insulins:-acting analogues to overcome limitations of
Ultrashort
short acting insulins(regular)
- Long acting analogues to overcome limitations of
long/intermediate acting insulins(NPH)
 LIMITATIONS OF REGULAR INSULINS
Regular insulins form hexamers which dissociate slowly into
monomers
thus delaying absorption.

Delayed onset of action (1/2 to 1

hr) Post prandial hyperglycemia

Prolonged time of peak action (2 to 3

hrs)
Duration of action (5 to 8 hrs) Late post prandial hypoglycem
Hence regular insulins cause a mismatch between need & availab
of bolus insulin and do not ideally mimic physiological bolus
secretion of insulin.
 OTHER LIMITATIONS OF
REGULAR
INSULINS
Regular insulin has to be administered 30-45mins before meal - d
of insulin cannot be adjusted according to size of meals.

Time of onset, peak action & duration of action is dose

dependent
(increases with dose)

Absorption varies with injection site & exercise (variability of

absorption
as much as 25%)
 ANALOGUES
Less propensity to form hexamers. Hexamers formed dissociate
rapidly
into monomers
Rapid onset of&action
are rapidly
- 10absorbed.
to Better control of post
20mins prandial glucose
Peak action – 1 to 2 hrs
Duration of action – 4 to 5 hrs Decreased risk of late post
prandial hypoglycemia

Mimics physiological bolus secretion.

o Can be taken just before or just after meals – allows adjustment

insulin
dose with size of meal.
o Onset of action & peak action independent of dose/site of
injection /
exercise.
 LIMITATIONS OF NPH
INSULINS
Doesn’t mimic physiological basal insulin
secretion
- Peak action 5 to 7hrs after administration ( risk of
nocturnal
hypoglycemia
- Duration(ifofadministered at bedtime) enough to cover
action not long(≈20hours)
insulin
requirements
Action profileofdepends
the wholeonday with a single injection .
dose.
Variability of absorption with site/exercise/variation in mixing of
suspension
(50%variability). Highly unpredictable action profile.
Continuous subcutaneous insulin infusion (CSII) through pumps
-Most physiological method of insulin delivery

-Preferred in patients uncontrolled on multiple

injections
-& those needing
Specially suitableexcellent control(pregnancy)
for patients with risk of
hypoglycemia,
uncertain lifestyles,meal times.
Consists of insulin reservoir, program chip, keypad&
screen. Insulin infused through plastic tubings
connected
to s/c inserted infusion set .
INSULIN DELIVERY – short acting insulin analogues like Aspart(lis
used.
Provides constant basal infusion of insulin & patient can activate
meal
boluses.
Pumps can be discontinued for short periods for activities like
exercise
Pump can be pre-programmed to compensate for nocturnal & ear
morning
glucose fluctuation.
Advantages
- Rate of insulin absorption more predictable than multiple
injections
- Risk of hypoglycemia less
Drawbacks
-Pump failure -
ketoacidosis
--Injection site abscess
Only motivated & commited patients can
use it.
INSULIN ANALOGUES IN SPECIAL
SITUATIONS
Diabetic ketoacidosis – Lispro
(i.v)
Pregnancy
Lispro & Aspart demonstrated efficacy&safety
(Cat B)
Long acting analogues not studied.
Children
Data on insulin analogues is
limited.
Elderly (at risk of hypoglycemia)
Insulin analogues preferred.
NEW DELIVERY SYSTEMS USING
ANALOGUES
Insulin pens (ultra short acting/long acting/pre-mix
analogues)

CSII pumps
(Aspart>Lispro)
Thank You