A detailed study of insulin medication from past to present & future. Different types of insulin medications their storage & safety condition along with the sites for the administration of insulin dosage forms.

1. MR. SHAKTIPRASAD PRADHAN
M . P h a r m , P h . D *
RESEARCH PROFESSIONAL, UDPS
shakti.pharma16@gmail.com
UTKAL UNIVERSITY, BHUBANESWAR
ODISHA, INDIA
.

2. 1
INTRODUCTION

3. 2
Insulin
Pancreas is primarily an exocrine gland & only 2%
accounts for the endocrine portion, which is made by one to
three millions of pancreatic islets.
The pancreatic islets are made by 65–80% of the beta
cells which synthesize the insulin hormone.
Beta cells are sensitive to blood sugar levels, so they
secrete insulin into the blood in response to high level of
glucose & inhibit their secretion when glucose level is low.
Insulin is produced from the pancreas in two different
ways.
I. Basal/ Background insulin is released 24 hours a day,
whether or not a person eats & regulates glucose levels
between meals.
II. Bolus insulin is released with direct response to the
ingestion of food in order to manage the rise in blood glucose
level that immediately follows. (Cont.)

4. 3
The molecular formula of human insulin is
C257H383N65O77S6 having a molecular mass of 5808 Da.
Insulin is derived from Proinsulin a 74 amino acid
prohormone molecule.
Human insulin is composed of 51 amino acids, a
combination of two peptide chains (hetero dimer)
Chain-A and Chain-B composed of 21 & 30 amino acids
respectively, linked together by two disulphide bonds.
Insulin was the first peptide hormone discovered and
also the first protein to be chemically synthesised &
produced by DNA recombinant technology.
It is included in the Model List of Essential
Medicines, the most important medications needed in a
basic health system, by the World Health Organization
(WHO).

5. 4
JOURNEY OF INSULIN

6. 5
Journey of Insulin
The discovery and advancement of insulin as an
antidiabetic medication can be traced back to the 19th
century.
Research into the development of insulin has motivated
scientists to take historic steps towards understanding
human biology, resulted a number of Nobel Prize awards
for the investigation.
In 1869, Paul Langerhans, discovered a distinct
collection of cells within the pancreas & later be called
the Islets of Langerhans.
In 1889, Oskar Minkowski & Joseph von Mering during
the study on pancreas effects on digestion found that
after removing the pancreas gland from dogs, they died
shortly. This led to the idea that the pancreas produces
some “Pancreatic substances” (Insulin). (Cont.)

7. 6
In 1901, Eugene Opie discovered that the Islets of
Langerhans produce some pancreatic substance
(Insulin) and diabetes resulted due to the damage of
these cells.
In 1910, Edward Albert Sharpey Shafer suggested
that only one chemical was missing from the pancreas
in diabetic people. He decided to call this chemical
Insulin, comes from the Latin word insula, meaning
“island.”
In 1921, Frederick Banting & Charles figured out
how to remove insulin from a dog’s pancreas.
In January 1922, Leonard Thompson, a 14 years old
boy with type 1 diabetes became the first human to be
given the first medical administration of insulin by
injection. (Cont.)

8. 7
In 1923, Banting and Macleod were awarded the
Nobel Prize in Physiology/ Medicine for these research.
In 1923, Eli Lilly produces commercial quantities of
much purer bovine insulin than previously used.
In 1936, D.M. Scott & A.M. Fisher both Canadian,
formulated a zinc insulin mixture and license it
to Novo.
In 1936, Danish physician Hans Christian Hagedorn
discovered the action of insulin can be prolonged with
the addition of protamine.
In 1946, Nordisk formulated Isophane porcine
insulin aka Neutral Protamine Hagedorn or NPH
insulin.
In 1950, Nordisk marketed NPH insulin an
intermediate acting insulin. (Cont.)

9. 8
In 1953, Novo formulated Lente porcine and Bovine
insulins by adding zinc for longer lasting insulin.
In 1955, Frederick Sanger sequenced the amino acid
sequence of insulin & insulin became the first protein
to be fully sequenced. In 1958 Sanger receives the
Nobel Prize in Chemistry for his research.
In 1965, insulin became the first human protein to be
chemically synthesised by Wang Yinglai, Chen Lu
Tsou, et al.
In 1978, Genentech biotechnology firm produced
biosynthetic human insulin in Escherichia coli bacteria
using recombinant DNA techniques which made
insulin, the first human protein to be manufactured
through biotechnology.
(Cont.)

10. 9
In 1983, Eli Lilly company produced Humulin, the
biosynthetic human insulin with recombinant
DNA technology.
In 1985, Novo Nordisk introduced the Insulin Pen
delivery system.
In 1996, Eli Lilly marketed the analogue
insulin Lispro under the trade name Humalog.
In 2000, Sanofi Aventis marketed Lantus insulin
glargine analogue.
In 2013, the University of Cambridge developed an
artificial pancreas that pairs the technology of an
insulin pump with a continuous glucose monitor.
In 2015, Dr Edward Damiano introduced the iLet (a
bridge to a cure) a bionic pancreas device that delivers
both insulin & glucagon every five minutes as required.

11. 10
IMPORTANCE OF
INSULIN

12. 11
Importance of Insulin
Primarily insulin is regarded as the hormone that
regulates blood sugar level.
After a meal insulin helps to metabolize & use food
for energy throughout the body so a problem with
insulin can have a widespread effect on any or all of the
tissues, organs and systems of the body.
Insulin helps the body to use or store the glucose
that's derived from carbohydrates in the diet.
In liver insulin stimulates the creation and storage of
glycogen from glucose. High insulin levels cause the
liver to get saturated with glycogen.
Insulin is important to overall health & survival, so
problems with insulin production or utilization, insulin
supplement is needed throughout the day. (Cont.)

13. 12
Insulin helps the amino acids in protein to enter
cells, so without adequate insulin production, this
process is slowed down, making it difficult to build
muscle mass.
Insulin also makes cells more receptive to
electrolytes like potassium, magnesium and phosphate.
These minerals help conduct electricity within the
body, so they influence muscle function, blood pH, and
the amount of water in the body. By causing excessive
urination (Polyuria) with water and electrolyte loss,
hyperglycaemia can worsen an electrolyte imbalance.
Insulin helps to transport glucose from the
bloodstream with the help of glucose transporters.
Insulin may even influence the development or
progression of Alzheimer disease.

14. 13
ADVERSE EFFECTS
OF
INSULIN MEDICATION

15. 14
Adverse Effects of Insulin Medication
There may be chances of mild or serious side effects
that occur during or after taking the insulin
medication.
The common side effects include
Low blood sugar (Hypoglycaemia)
Swelling of arms and legs
Weight gain
Short term salt & water retention (Peripheral edema)
Injection site reactions: Redness, swelling, itching
Skin changes at the site of injection (Lipodystrophy):
Can be managed by changing or rotating the injection
site. (Cont.)

16. 15
Serious side effects can be life threatening if left
untreated, which include
Severe low blood sugar:
Loss of consciousness, confusion including delirium,
tingling or numbness in lips or tongue, blurred or
impaired vision, seizures.
Low blood potassium (Hypokalemia): Breathing
problems, heart rhythm problems, muscle cramps,
tiredness.
Serious allergic reaction: Rash all over the body,
trouble breathing, fast heart rate, sweating, feeling
faint.
Swelling of hands and feet.
Heart failure: Shortness of breath, swelling of
ankles or feet, sudden weight gain.

17. 16
INSULIN LINKED
MAJOR ABNORMALITIES

18. 17
Insulin Linked Major Abnormalities
Type 1 diabetes (T1D):
It is an autoimmune disease & a chronic condition
in which the pancreas produces little or no insulin.
It typically appears in adolescence, supplemental
insulin is vital but not always.
Treatment aims at insulin therapy, diet &
exercise.
Type 2 diabetes (T2D):
It is a chronic condition in which insulin
production is lower than normal and/or the body
isn't able to use it efficiently.
There is no cure for T2D but can be managed by
diabetic medication or insulin therapy, diet, exercise
& weight loss. (Cont.)

19. 18
Insulin resistance:
It can be due to a problem with the shape of the
insulin (preventing receptor binding), not having
enough insulin receptors, signalling problems, or
glucose transporters not working properly & can
occur as a result of excess body fat.
Treatment includes insulin therapy, diet, physical
exercise losing weight.
The Dawn effect:
It is an observed increase in blood sugar (glucose)
levels takes place in very early morning, often
between 2 am and 8 am, so an increase insulin
demand occurs at dawn.
It correlates the insulin, blood sugar (glucose) &
night sleep. (Cont.)

20. 19
This is a natural occurring phenomenon happens
to nearly everyone with diabetes, affecting their
medical management.
If you have diabetes, your body doesn’t release
more insulin to match the Dawn effect/
phenomenon.
There are a few ways to prevent the Dawn effect,
including
By adjusting the dose of insulin or other diabetic
medication.
Not eating carbohydrates closer to bedtime.
Taking insulin closer to bedtime instead of closer to
dinner time.
Doing some light physical activity like walking,
jogging, yoga after dinner.
By using an insulin pump overnight.

21. 20
TYPES OF INSULIN
MEDICATION

22. 21
Types of Insulin Medication
The types of insulin medication are characterized by
three different characteristics.
1. Onset: Time taking for the insulin to start
lowering blood glucose level.
2. Peak time: After an injection the time when the
insulin is most effective at lowering blood glucose
level.
3. Duration: Total time continue to work for lowering
blood glucose level by the insulin.
Insulin is prescribed by matching the characteristics of
particular insulin with the individual needs of the patient.
Some patients need only one kind of insulin, while
others take a combination of insulin medication to
customize good glucose control. (Cont.)

23. 22
Currently seven different categories of insulin
medications are available.
1. Rapid acting: Onset of less than 15 minutes, peak
at 30 to 90 minutes & duration of 2 to 4 hrs. Apidra,
Humalog, Novolog.
2. Short acting (Regular): Onset of 30 minutes, peak
at 2 to 3 hrs & duration of 3 to 6 hrs. Humulin R,
Novolin R.
3. Intermediate acting: Onset of 2 to 4 hrs, peak at 4
to 12 hrs & duration of 12 to 18 hrs. Humulin N,
Novolin N.
4. Long acting: Onset of several hrs, minimal or no
peak & duration of 24 hrs or more. Levemir,
Lantus.
(Cont.)

24. 23
5. Ultra long acting: Onset of 6 hrs, no peak &
duration of 36 hrs. Toujeo.
6. Combinations/ Pre mixed: Onset of 15 minutes to 1
hr, peak time varies depending on the mix. &
duration up to 24 hrs. Mixtures of Humulin or
Novoline, Novolog Mix, Humalog Mix. Combination
of intermediate acting insulins with regular insulin.
7. Inhaled insulin: Onset of 12 to 15 minutes, peak at
30 minutes & duration of 3 hrs. Afrezza.
Combination of long acting insulin. Approved by the
USFDA in 2014 & became available in 2015.
 Different types of insulin medication, how long they
will take to start lowering blood sugar, when the
peak of action will occur and how long they will
continue to work, all are summarized in Table-1.

25. Table-1: Some Important Insulin Medication

26. Onset, Peak & Duration of Insulin Types

27. 26
STORAGE & SAFETY OF
INSULIN MEDICATION

28. 27
Storage & Safety of Insulin Medication
The efficacy of insulin medication may be affected by a
wide range of change in temperature (extreme hot or
cold), powerful sunlight and improper storage conditions
(after & before opening).
Unopened insulin should always be stored in a cool
condition or at room temperature (15°C to 25°C & up to
30°C or 59°F to 77°F) or normal storage conditions as per
the IP, as injecting cold insulin can sometimes be more
painful.
At room temperature, insulin vial can generally last
about one month, once opened & insulin pens can only
last about 28 days.
A vial of insulin is considered open if its seal has been
punctured & if the cap is removed but the seal isn't
punctured, the bottle will be considered unopened. (Cont.)

29. 28
Expired insulin will no longer be potent or effective, so
it should be discarded after the date of expiry.
To use an insulin medication safety precautions should
be adopted:
By keeping the insulin medication out of direct heat
or sunlight.
By keeping the patient shaded, while administering
insulin.
By discarding or refusing any degraded quality
insulin medication having an unusual appearance as
cloudy or not clear, appearance of small crystals,
clumps even after rolling it between the palms.
By avoiding dosage related mistakes, so never guess
the insulin dosage, never share the insulin vials with
anyone, check insulin dosage each time before taking
a dose.

30. 29
DOSES OF
INSULIN MEDICATION

31. 30
Doses of Insulin Medication
Insulin supplemental doses may be prescribed during
illness, patients with type 2 diabetes receiving oral
medications may be switched to insulin therapy
temporarily.
The daily doses of insulin medication may be higher
during illness, stress, pregnancy, in obese patients,
trauma, during concurrent use with medications
having hyperglycaemic effects or after surgery.
Daily doses of insulin medication may be lower with
exercise, weight loss, calorie restricted diet, during
concurrent use of hypoglycaemic medications.
Individualize dose is based on the metabolic needs (in
T1D & T2D), frequent monitoring of blood glucose level
(in T1D & T2D) & HbA1c values (only in T2D). (Cont.)

32. 31
Regular human insulin is a short acting prandial
insulin available in 2 concentrations as U-100 (100
units of insulin per mL) & U-500 (500 units of insulin
per mL).
To avoid any mix up with the availability of 2
different regular human insulin concentrations, insulin
doses should always be ordered in units not in volume.
Insulin resistant patients requiring daily insulin
doses of more than 200 units may find U-500 insulin to
be useful as large doses may be administered
subcutaneously in a reasonable volume.
For T1D total daily insulin requirements are
generally between 0.5 to 1 unit/kg/day & for T2D the
initial doses are often in the range of 0.2 to 0.4
units/kg/day. (Cont.)

33. 32
Most individuals with Type-1 or Type-2 diabetes
should be treated with insulin medication, as multiple
daily insulin (MDI) injections, continuous
subcutaneous insulin infusion (CSII), intravenous
administration, infusion fluids etc.
Multiple daily insulin (MDI) injections
Combination of bolus/ prandial (rapid or short acting)
and basal (intermediate or long acting) insulin.
Administered subcutaneously into the abdomen,
buttocks, thigh or upper arm within 30 minutes before
a meal, injection sites should be rotated within same
region to reduce the risk of lipodystrophy.
U-100 regular human insulin may be mixed with
NPH insulin & U-500 regular human insulin should
not be mixed with other insulins. (Cont.)

34. 33
Dose for T1D is U-100 insulin s.c 3 or more times, U-
500 insulin s.c 2 to 3 times a day approximately 30
minutes prior to start of a meal.
Dose for T2D is U-100 insulin s.c 3 or more times, U-
500 insulin s.c 2 to 3 times a day approximately 30
minutes prior to start of a meal. May be used in
combination with oral antihyperglycemic agents or
longer acting basal insulin.
Continuous subcutaneous insulin infusion (CSII)
Insulin pump therapy.
Intravenous administration
U-100 insulin is administered by both i.v & s.c route,
but U-500 regular human insulin should not be
administered intravenously (i.v) only by s.c.
Infusion fluids
Humulin R & Novolin R. (Cont.)

35. 34
The dose of insulin medication may be altered
when the brand, type or species of insulin is changed,
during stress, major illness or with changes in
exercise, meal patterns or co administered drugs.
The daily doses of insulin medications are quite
different for the patients with kidney diseases, liver
diseases, heart failure, low blood potassium level
(hypokalemia), who are pregnant and breastfeeding
women.
Insulin may pass into breast milk and get broken
down by the child’s stomach so the amount of insulin
needed for breastfeed may change.
However insulin doesn’t cause side effects in
children who are breastfed by mothers with
diabetes. (Cont.)

36. 35
Daily insulin medication doses can be tough to
manage, but developed new technology with
sophisticated algorithms, can easily calculate how
much insulin a patient needs per dose.
Some are connected to specific prescription insulin
pens and some are calculating applications that
anyone can use.
Some common & popular apps for calculating the
insulin doses are mySugr, PredictBGL, Diabetes:M,
Insulia, InCalc, RapidCalc, BlueStar (approved by
the FDA), Accu-Chek etc.

38. 37
However the daily doses of insulin medications are
quite different for the
 Patients with kidney disease
 Patients with liver disease
 Patients with heart failure
 Patients with low blood potassium level
(Hypokalemia)
 Women who are pregnant
 Women who are breastfeeding:
• Insulin may pass into breast milk and get broken
down by the child’s stomach.
• Insulin doesn’t cause side effects in children who
are breastfed by mothers with diabetes.
•However, if you breastfeed, the amount of insulin
you need may change.

39. 38
DELIVERY DEVICES FOR
INSULIN MEDICATION

40. 39
Delivery Devices for Insulin Medication
There are a number of types & forms of devices to
deliver or administer insulin medication.
Insulin injection
Insulin cannot be taken as a pill or tablet because
digestive enzymes would break it down before it could
get into the bloodstream, for that reason it must be
injected.
Insulin pen
Two types of insulin pens are available as insulin filled
cartridge pen containing an insulin filled cartridge &
pre filled disposable insulin pen meant to be discarded
after all the prefilled insulin has been used.
For both types, the insulin dose is "dialed" on the pen
& injected through a needle. (Cont.)

41. 40
Insulin jet injector
Insulin jet injectors are designed for people who
find insulin injections uncomfortable or unsettling in any
way.
Jet injectors are designed to send a fine spray of insulin
through the skin using a high pressure air mechanism.
However, this product remains relatively rare and also
needs to be regularly boiled and sterilized.
Insulin patch
This is a credit card size device that adheres to the skin
& the insulin patch holds a small reservoir and a pre
filled needle.
Insulin is triggered by pressing a button on the patch &
it is designed to deliver both a continual flow of basal
insulin and individual doses of bolus insulin. V-Go is an
insulin patch marketed device. (Cont.)

42. 41
Insulin pump
Consisting of a reservoir to hold insulin & a pump,
these devices connect to the body via tubing and use a
cannula holding a needle for delivering insulin into body.
These devices provide a slow, steady stream of fast
or short acting basal insulin, with an option to deliver a
larger dose of additional insulin (bolus) at meals.

43. 42
SITES OF
APPLICATION FOR
INSULIN MEDICATION

44. 43
Sites of Application for Insulin Medication
Typically, insulin absorption is fastest in the abdomen,
somewhat less quickly in the upper arms, slower in the
thighs and slowest in the buttocks.
Usually it is recommended to deliver mealtime insulin
injections in abdomen, as they work fastest which helps
to lower post prandial (after meal) blood sugars.
Long acting insulin, such as Lantus or Toujeo, can be
injected into a slower absorption site, such as the
buttocks or upper thigh, upper arm so that the
absorption can happen gradually, covering the insulin
needs throughout the night.
However the best way to control blood sugar level is to
aim, to use the same site at the same time of day and
daily to rotate within that site. (Cont.)

47. 46
Fatty tissue:
Insulin is meant to be injected subcutaneously
(under the skin) into fatty tissue, such as the
abdomen, outer parts of thighs, backs of arms and
buttocks.
Injecting insulin in fatty tissue helps the body to
absorb insulin slowly and predictably, this layer of
skin sits on top of the muscle and has fewer nerves,
which can make injections more comfortable.
Abdomen:
Injecting insulin into the abdomen is very common
amongst people with diabetes as the insulin
absorption is fastest here and a greater surface area
as well as less muscle, making it more comfortable &
easier to rotate injections sites. (Cont.)

48. 47
Backs of arms:
Injecting in the upper arm, using only the outer
back area is also a good site (where the most fat is).
Upper buttocks or love handles:
The love handles, area just above hip, is a good
injection site for young children or very thin adults,
as usually able to squeeze a small amount of fat.
Outer side of thighs:
The outer, fattier part of the thigh is also a good
site for insulin injection and not the inner thighs.

50. 49
TIPS FOR INSULIN
ADMINISTRATION

51. 50
Tips for Insulin Administration
Injecting into the same exact spot on the same site
repeatedly can cause the skin to develop hard lumps or
extra fat deposits, so it should be avoided.
If lumps and bumps are developed at injection sites,
then the area of the bump should be avoided for several
months as that area will absorb insulin differently
affecting blood sugar level.
Sites that are exercising, should be avoided for insulin
injection, as this can increase the risk of hypoglycaemia
due to increased absorption.
Using impure insulin may result in fat atrophy.
A painless injection seems positive, but this can
damage the skin more, so this is not a good sign.
Injecting into moles or scar tissue should be avoided, as
these can also affect insulin absorption.

52. 51
REFERENCES

53. 52
1. https://www.drugs.com/drug class/insulin.html.
2. https://en.wikipedia.org/wiki/Insulin_(medication).
3. https://medlineplus.gov/druginfo/meds/a682611.html.
4. American Diabetes Association 2018 Annual
Report (PDF).
5. Classification & Diagnosis of Diabetes: Standards of
Medical Care in Diabetes—2019. American Diabetes
Association Diabetes Care 2019 Jan; 42(Supplement
1): S13-S28. https://doi.org/10.2337/dc19-S002.
6. https://www.endocrineweb.com/guides/insulin/insulin-
delivery.
7. https://www.diabetes.co.uk/insulin/Diabetes-and-
insulin-delivery-devices.html.
8. https://www.diabetesselfmanagement.com/diabetes-
resources/tools-tech/insulin-delivery-devices/.
9. https://pubmed.ncbi.nlm.nih.gov/2226111/.

54. .
Thank You