Insulin sensitivity n delivery method

1. Dr. ANUJ KUMAR
JR-II General
Medicine.

2. Routes of Insulin administration

3. SUBCUTANEOUS
ROUTE
A) Vials and
Syringes
B) Insulin Pens
C) Insulin Pumps

4. Insulin can be administered subcutaneously via various methods such as vial and
syringe, insulin pen and continuous subcutaneous insulin infusion (CSII)
Though subcutaneous insulin delivery is the standard route of insulin administration, it is
associated with injection pain, needle phobia, lipodystrophy, noncompliance and peripheral
hyperinsulinemia
Each method has its own advantages and disadvantages.

5. Vial and Syringes
The development of syringes dates back to 1853 (Fergusson syringe) that paved the way for the
development of the modern syringes.
In 1924, 2 years after the discovery of insulin, Becton, Dickinson and Company (BD) made a
syringe specifically designed for the insulin injection.
• To reduce the incidence of needle associated infections, disposable syringes were developed.
BD mass produced the first glass disposable syringes in 1954, called the BD Hypak
Despite all the advancements in modern syringes, many patients do not feel to inject insulin 3-4
times a day as a result of needle phobia

6. Recently, an injection port has been designed know as i-port Advance•.
It is the first device to combine an injection port and an inserter in one complete set that
eliminates the need for multiple injections without having to puncture the skin for each dose.
This device is helpful for the insulin requiring patients having needle phobia and helps them to
achieve glycemic control effectively

7. I -Port Advance
•The i-Port is applied with a virtually
painless insertion, leaving a soft
cannula under the skin and giving you a
means to inject medications, with
fewer
punctures, over three days of normal
activity (including showering, swimming
and exercising). It is compatible with
pens and syringes and can be used by
children and adults.
/
-- ""'"""
"'
• If you take an average of five shots a day, you can reduce the number of times you poke yourself from
150 to 10
in just 1 month! That's 93%less pokes.

9. Syringe
s
• Syringes come in different sizes.
• Each line on a 100-unit syringe marks 2 units of insulin.
• Each line on a SO-unit or 30-unit syringe marks 1 unit of
insulin. Use a syringe large enough to hold the whole dose of
insulin.
• The standard needle is 1/2-inch long.
• Needles also come in 5/16-inch and 3/16-inch lengths.
• The 3/16-inch length is often used for children.
The thinner the needle, the higher its gauge

11. B)lnsulin
Pens
Insulin pen injectors are convenient and discreet way of administering insulin. They have a built-in dial
that allows us to determine the amount of insulin to be injected, a short needle at one end and a plunger at the
other.
Insulin pens are particularly useful if we need to take premixed insulin
The first insulin pen was manufactured by NovoNordisk in 1985. This was followed by refinements by various
pharmaceutical companies over the past 30 years
The newer insulin pens are reusable, more accurate and equipped with safety features such as audible clicks
with each dose to improve accuracy and reduce the chances of human errors

13. Another advancement in the pen device includes:-
• (HumaPen• Memoir'") is built-in recording of the time and date of the last 16 injections.
NovoPen Echo• has been designed to give children and parents increased confidence, combines
dosing in half-unit increments with a simple, easy to use, memory function.
• Recently developed pen needles are shorter and thinner (31-32 G x 4-5 mm), less painful and
requires less thumb force and time to inject insulin resulting in improved patient satisfaction
The newer smart pens are designed to guide the individual about the insulin dosage {by means
of inbuilt calculators), they have memory functions to remember the amount and time of insulin
dosage and automatic transmission of insulin dose to the mobile logbook through Bluetooth
technologies.

14. Insulin Pen ( Novolog Flexpen)
Resl:11.81
sa,le
Rtriduil e
Push
butcn

15. PATIENT
COUNSELLING
• Method of administration

16. Method of Administration
Prepare the skin.
• Prime the pen.
• Check the pen for air bubbles ( Safety Check) Dial the
required dose of insulin
• Inject at a 90-degree angle. Expose the site of injection
Safely dispose the injected needle in a solid lid
container

18. Insulin Pumps
Insulin pumps are small devices of size of a pager that can be attached to our belt or placed in our pocket.
They are made up of an insulin reservoir connected to a tube, ending in a cannula or catheter, which is
inserted under the skin of our abdomen.
They can be set to deliver insulin at a slow, continuous rate throughout the day, or to release larger quantities
at meal times or when blood sugar is high.
The main advantage of a pump is that it closely mimics the slow but continual release of insulin by the
pancreas
At present due to its prohibitive cost its usage is very limited. All patients who qualify for insulin pump therapy
should be referred to a centre where expertise for a pump is available.
Pump therapy requires a lot of motivation and time from both the patient and the clinician

22. Indications
All Type -1 diabetics who are poorly controlled with basal-bolus therapy.121
Pregnancyl1J
Frequent hypoglycemia or hypoglycaemic unawareness Ill Persistently elevated fasting glucose
(Dawn phenomenon) !ll
Multiple chronic complications with labile glucose requiring fine tuning of glycemic control
Ill
Management of labile diabetes after renal or hepatic transplant 121
In situations where insulin requirement is very high a trial of pump therapy can be given.

23. Types of Insulin Pumbs
Continuous Subcutaneous Insulin Infusion (CSII)
Implantable insulin pumps
Closed insulin delivery system with CGMS insulin delivery (artificial endocrine pancreas) Nano
pump with closed insulin delivery system and continuous glucose sensing.

25. INHALED
INSULINS
- Exubera
- Afrezza
- Aerodose,
Promax

28. Exubera ( by
Pfizer)
Approved by US FDA in 2006 and it was later withdrawn in 2007
• It was available as lmg,3mg dry powder form that to be taken with inhaler
It was found to have pharmacokinetic and pharmacodynamic (PK/PD) properties similar to
insulin aspart with a faster onset of action (10-15 min.
• In clinical trials in patients with uncontrolled TlDM and T2DM, Exubera• was found to reduce
postprandial blood glucose.
• However, Exubera• was contraindicated in smokers as it increased the risk of hypoglycemia
due to greater absorption compared to nonsmokers.
patients were required to undergo pulmonary function tests before treatment initiation,
after 6 months and annually thereafter.

29. Advantages
Noninvasive
Patient compliance
• Rapid onset of action (10-15 min) Better
PPBG control
Disadvantages
• Bulky delivery device
•Patient need to undergo frequent PFT
• Expensive

30. Afrezza
• Prescription Afrezza• is a man-made rapid-acting mealtime inhaled insulin breathed in through
your lungs and is used to control high blood sugar in adult patients with diabetes.
• FDA-approved AFREZZA is the only inhaled insulin working to help control blood sugar during
mealtime.
• When using the AFREZZA inhaler at the beginning of a meal, insulin enters the bloodstream
through your lungs.
AFREZZA is rapid acting mealtime insulin that starts to work in approximately 12 minutes, peaks at
about 35 to 45 minutes and is done working in 90 to 180 minutes (for the 4 unit and 12 unit
respectively). For the 48 unit dose,it starts working in about 12 minutes, peaks at about 55
minutes and is done working in approximately 4.5 hours.

31. CONTRAINDICATIONS
AFREZZA is contraindicated in patients: During episodes of hypoglycemia.
With chronic lung disease (such as asthma or chronic obstructive pulmonary disease
[(COPD)) because of the risk of acute bronchospasm.
With hypersensitivity to regular human insulin or any of the AFREZZA excipients.
SIDEEFFECTS
Hypoglycemia (sweating, confusion, headache, blurred vision, slurred speech etc) Decreased
Lung function
Severe allergic reactions Hypokalemia

32. Limitations
• AFREZZA is not a substitute for long-acting insulin. AFREZZA must be used in combination with
long-acting insulin in patients with type 1 diabetes mellitus.
• AFREZZA is not recommended for the treatment of diabetic ketoacidosis.
• The use of AFREZZA is not recommended in patients who smoke or who have recently stopped
smoking (less than 6 months).
It is not known if AFREZZA is safe and effective in children under 18 years of age.

33. FUTURE
TRENDS

34. • AERODOSE
• TECHNOSPH
ERE
• AERx
Advanced inhalational
research devices
currently under Phase
3 : result awaited
Challenges
•Technical issues
•Cost
•Long Term Safety

35. ORAL & BUCCAL
INSULIN

36. ORAL INSULIN
Oral route of insulin administration may be the most patient friendly way of taking insulin and it
could more closely mimic physiological insulin delivery
Natural and synthetic nanoparticles have been used as a carrier or vehicle for insulin such as
chitosan, liposomes, polymeric nanovesicles, polylactldes etc inorder to overcome the main
challenge of oral insulin : poor bioavailability
Combination of Self-Nano Emulsifying Drug Delivery System (SNEDD's) and Thiolated Chitosan is
promising and innovative approach to improve bioavailability

37. BUCCAL INSULIN
Initially, Generex Biotechnology developed Oral-lyn, which is a liquid formulation of
short acting insulin that is administered using Generex's metered dosage aerosol
applicator (RapidMist'M).
Phase 1 and 2 trials showed progressive report, currently its under phase 3 studies
Another molecule being developed by Shreya Life Sciences Pvt. Ltd., India is oral
Recosulin• and the results of the phase 2 and phase 3 trials are awaited
Another formulation "insulin loaded orally dissolved films" is undergoing PK/PD
investigation

38. NASAL
INSULIN

39. • Currently, two technologies are under investigation: Nasulin'M {CPEX pharmaceuticals) and
nasal insulin by Nastech Pharmaceutical Company Inc.
• Both insulin preparations have bioavailability of about 15-25% with the onset of action
~10-20 min.Results from the phase 2 and 3 clinical trials are awaited.
• Intranasal delivery has several advantages over oral (bypass GI peptidases), subcutaneous
(noninvasive and painless) and inhalation route (no issue with lung function) which makes this
route attractive for the delivery of insulin.
Intranasal delivery has shortcomings such as limited permeability of a large molecule through the
nasal mucosa and rapid mucociliary clearance resulting in variable absorption.

40. TRANSDERMAL
INSULIN

41. Trans-dermal insulin delivery eliminates the problems associated with needles and injections and
large surface area of the skin makes it a convenient route for insulin delivery.
However, the penetration of insulin is halted by the stratum corneum, the outer most layer of the skin.
Numerous methods have been explored to overcome the barrier of stratum corneum.
(a) lontophoresis, the technique that uses small electric currents (bl Sonophereis or phonopheresis uses
ultrasound waves,
(c) Microdermal ablation by removing the stratum corneum,
(dl Electroporation utilizes high voltage pulses that are applied for a very short lime
e) Transfersulin is the insulin encapsulated in transferosome, an elastic, flexible vesicle which squeeze by itself
to deliver drugs through skin pores
(fl lnsupatch'", a device developed as an add-on to an insulin pump that applies local heat to the skin in order to
increase the absorption of insulin

42. INTRA-PERITONEAL
INSULIN

43. Direct delivery of insulin in the portal vein mimics the high portal insulin concentration. This
route of insulin delivery has been investigated since the 1970s.
The pump (The MIP 2007C Medtronic/Minimed, Northridge, CA, USA) is implanted
beneath the subcutaneous tissue in the lower abdomen under general anesthesia.
From this subcutaneous pocket, the peritoneum is opened, and the tip of the catheter is
carefully inserted and directed towards the liver.
After implantation, the pump reservoir is refilled in the outpatient clinic transcutaneously at
least every 3 months, depending on the individual insulin requirement.
•Clinical trials have shown safety and efficacy of intraperitoneal insulin delivery.
•The limitations of this route of insulin administration include it is invasive, may be
associated with subcutaneous infections, cannula blockage, higher cost, portal-vein
thrombosis and peritoneal infection

44. FUTURE
TRENDS

45. Islet cell
transplantation
►This is a recently developed surgical procedure • called the Edmonton protocol • whereby islet
cells
from a donated human pancreas are injected into the liver ofa recipient with type 1 diabetes.
►The transplanted cells begin to secrete insulin, while the recipient needs to take immunosuppressive
medications for life to prevent rejection of the transplanted tissue.
►Clinical trials continue to establish the safety and long- term effectiveness of this procedure as a
means of supplying Insulin.

46. • GENE THERAPY
Scientists have Identified a gene called SHIP2 that appears to regulate Insulin. Such findings make SHIP2 a
potential gene therapy target for the treatment of type 2 diabetes aimed at improving the individual
insulin regulation.
A protein that blocks the overgrowth of blood vessels in the eye is being studied as possible gene therapy
for diabetic retinopathy.
A recent study showed that treatment with the protein, called pigment epithelium-derived factor, or PEDF,
prevented excessive new blood vessel formation in an animal model of retinopathy.
It may also be used to treat macular degeneration.

47. OTHER
NONCONVENTIONAL
ROUTES

48. • Ocular route
- Until date, no human trial has been reported with this route and an animal study failed to achieve
significant plasma insulin concentration.
Rectal route
- Rectal gels and suppositories showed fair results. However, this route is not commercially viable.
Intra-tracheal
- _Administration of insulin was reported in 1924 but is not practical so not taken up for further
development.

49. CONCLUSIO
N

50. There is a long history of research focusing on Identifying a route of administration for
insulin that is minimally or noninvasive, effective, safe, convenient and cost-effective for
patients.
Each route and delivery method has its own potential advantages and disadvantages.
•However, if successful, alternative routes of administration could revolutionize the
treatment of diabetes mellitus and help improve patients' quality of life.
•The success of commercial technologies and the emergence of new ones will be
demonstrated only with time.
•An oral delivery system of insulin will have tremendous benefits in terms of a decreased
number of injections for diabetic patients and a reduced incidence of side effects.

51. Thank You