Insulin Injections

Introduction

In 2017, the Malaysian Diabetes Educators Society published the Forum for Injection Technique Malaysia (FIT-MY) to provide evidence-based injection technique recommendations for people with diabetes mellitus who use injectable therapy in their daily management.

Proper subcutaneous administration of diabetes injectable medications requires careful consideration of factors such as

The injection sites
Needle length
Use of a lifted skin fold
Angle of injection

NovoPen 3, NovoPen 4, NovoPen 5 and NovoPen 6

Although NovoPen 4 has been phased out and replaced by NovoPen 5 in the UK, NovoPen 4 is still marketed in Malaysia.

NovoPen 5 offers an additional feature of a digital display that shows the dose memory.

Time elapsed: Each segment represents an hour since the last injection.
Last dose volume: Records the last insulin dose in units.

On other hand, NovoPen 6 is a new, smart insulin pen with NFC (Near Field Communication) technology that automatically record insulin dosing information about each injection.

Insulin dosing information

Time and date of all injected doses
The number of units dosed

To transfer the injection history to smartphone.

Hold the dose memory of the pen straight against the NFC spot on your device.
Wait while while your injection details are automatically transferred to a compatible app on your device.

Although NovoPen 3 is no longer supplied to newly started patients, it is good to be aware of the significant improvements in NovoPen 4 in case you encounter rare cases of old patients still using NovoPen 3).

One improvement in NovoPen 4 is the way the piston rod is pushed back.

In NovoPen 3, the end of the reset mechanism needs to be turned clockwise until it is no longer sticking out.
Whereas in NovoPen 4, the piston can be easily pushed back by gently pressing the piston head in until it stops.

Another difference between NovoPen 3 and NovoPen 4 is the process of resetting the dose to zero.

NovoPen 4 allows you to turn the dose button until the correct dose aligns with the dose indicator once you select a different dose.
In NovoPen 3, the process is more complicated. To reset to zero, you need to....

Grasp the cartridge holder with your thumb and forefinger.
Grasp the barrel between your thumb and middle finger.
Pull the cartridge holder down from the barrel as far as it will go (arrow #1)
Press the push button down with your index finger to reset the dose to zero (0) (arrow #2).
Check the dose indicator to make sure you have reset it all the way to zero (0).
If you have not, repeat steps above.

Furthermore, NovoPen 4 offers benefits to diabetic patients with manual or visual improvement.

INSUPen EZ and INSUPen Pro

INSUPen EZ and INSUPen Pro are reusable pens that can deliver insulin doses from 1 unit to 60 units in increments of 1 unit.

They can be used with insulin preparations of 100 IU/ml, specifically Biocon's Insugen-R, Insugen-N and Insugen-30/70 and Basalog.

Here are some differences between the two pens.

Colour

INSUPen EZ - Grey
INSUPen Pro - Green

Designed life

INSUPen EZ - Designed to be used for 2 years
INSUPen Pro - Designed to be used for 3 years

Method to reset the plunger rod

INSUPen EZ - Grip the plunger return ring. With the other hand rotate the pen body so that the plunger moves into the pen body. Continue rotating until the plunger rod stops against the plunger return ring.

INSUPen Pro - Grip the pen body in one hand and gently push back the plunger rod with the outer hand in to the injection mechanism section of the pen.

Indication of select more units than remaining in the cartridge

INSUPen EZ - You cannot rotate the dose knob to the required number of units when it exceeds the units left in the cartridge.
INSUPen PRO - When injecting, the injection button stops halfway and zero is not indicated, signalling that there are no units left in the cartridge.

Pen Needles

Ideally, pen needles should be used once only to avoid complications.

There is a probable association between reused needles and the presence of lipohypertrophy, although a direct causal relationship has not been proven.
Reused needles may cause pain, bleeding and bruising at injection site.
Plus, reused needles may cause the insulin in the barrel to crystalise and block its flow during the next injection.

After use, needles should be disposed immediately and should not be left attached to the pen.

Leaving the needle attached allows the entry of air and other contaminants into the cartridge or causes leakage of insulin from the cartridge, which can affect subsequent dose accuracy.

However, it is unfortunate that not all patients can afford to use new needles for each injection.

Pen Needles Length

Pen needles come in various lengths, such as 4 mm, 5 mm, 6 mm and 8 mm with different gauge.

Recent studies have demonstrated that minimal difference in skin thickness exists between adults of different age, gender and BMI, that is from approximately 1.25 mm to 3.25 mm in 90% of individuals.

On the other hand, children have been shown to have a smaller skin thickness, which increases gradually from birth to adulthood.

For most individuals using a short pen needle (4 or 5 mm), the risk of intramuscular injection is low and the needle can be inserted perpendicularly (at a 90° angle to the skin surface) without a skin fold. Moreover, they are usually better tolerated.

The use of 4 mm needles for overweight and obese people is efficacious with no loss of safety, efficacy or tolerability, and no evidence of worsening metabolic management.
A 4- or 5-mm pen needle may cost more to a patient than a 6 mm pen needle.
In comparison, a perpendicular injection in a lean area with an 8 mm pen needle may result in an intramuscular injection, from which absorption is more rapid. Hence, an 8 mm pen needle should be injected with a skin fold and at 45°. When this translates into practice, it is very inconvenient.

More info can be found at Clinical Guiding Principles of Subcutaneous Injection Technique, 2019.

Rotating Insulin Injection Sites

Human insulins are absorbed fastest from the abdominal wall, slowest from the leg and buttock, and at an intermediate rate from the arm. These differences can be useful clinically.

Pre-meal regular insulin should be rapidly absorbed, and injection into the abdominal wall may therefore be preferable.
Rapid-acting insulin absorption is increased when the insulin is injected into an exercising limb due to increased blood flow.
Pre-evening meal dosing of intermediate-acting insulin should be slowly absorbed to ensure a duration of action that lasts through the night, and injection in the leg or buttock may be preferable.

NOTE: The absorption of the long-acting basal insulin analogues, glargine and degludec, do not appear to be significantly influenced by injection site

For ease of self-injection, the abdomen and thighs are the two main recommended injection sites for adults.

Patients are counselled to rotate the injection site to prevent development of lipohypertrophy.

According to Ministry of Health counselling guide, for abdomen site injections, it should be 3 fingers away from navel and patients should not inject at the same time for the next injection (i.e. 2 fingers away from the previous injection site).

However, it may be better if we suggest patients to divide the abdomen to four quadrant (or halves when using thighs and buttocks) and the injections should then done systemically to ensure the same injection site is going to be injected again at least a week later.

If a patient is on basal-bolus regimen, patients would have to inject 4 times a day. They may easily lose track of the last injection site.

NOTE:

Massaging the site before or after injection may speed up the absorption. Hence, it is not recommended.
Higher skin temperature (e.g. sauna or hot bath) may increase the absorption rate of insulin.

Currently, majority of lipohypertrophy in people with diabetes develops due to a lack in injection site rotation. In real life, some patients prefer to inject at these lipohypertrophic sites since these areas have limited nerve innervations and thereby render the injections to be relatively painless. However, lipohypertrophic site injection may decrease or cause variability in the rate of insulin absorption.

In fact, switching injections from lipohypertrophic to normal tissues often requires a decrease in the dose of insulin injected. Although the exact amount of insulin reduction varies from one individual to another and should be guided by frequent blood glucose measurements, reduction often exceeds 20% of their original dose.

Insulins Stability

Based on Toujeo website, the in-use stability of Toujeo is up to 8 weeks (56 days) at room temperature (temperature below 30°C).

This recommendation is in contradict with the product leaflet of Toujeo marketed in Malaysia and Medicines Compendium UK (may be stored for a maximum of 6 weeks below 30°C).
The difference is due to different legal requirements across countries when registering new product.

Is there any insulin marketed in Malaysia which has an in-use period longer than 28 days?

The in-use shelf life for the insulins listed below are all 6 weeks when stored below 30°C.

Insulin Actrapid, Insulatard, Mixtard
Insulin Insugen-R, Insugen-N and Insugen 30/70
Insulin detemir (Levemir)

Insulin degludec (Tresiba) has an in-use shelf life of 8 weeks.

Quick Count on Insulin Needed

If a patient is on Insulin Actrapid 26 IU TDS and Insulin Insulatard 24 IU ON, how many insulin refill cartridges will this patient require for each month (30 days)?

The shortcut will be to calculate the total daily dose per day, and then divide it by 10.

The answer will be insulin refill cartridge required.
This shortcut is only applicable for insulin pen or refill cartridge which contains 300 IU each.

Hence,

Insulin Actrapid = 26 * 3 / 10 = 7.8 cartridge.

Insulin Insulatard = 24 / 10 = 2.4 cartridge

Hence, the patient will need 8 Insulin Actrapid refill cartridge and 3 Insulin Insulatard refill cartridge per month.

Somogyi Effect

In simple terms, Somogyi effect is a rebound hyperglycaemia. It is quite fascinating to think how our body trying to achieve homeostasis. Over the night, insulin-induced hypoglycaemia caused our body to respond by releasing counter-regulatory hormones such as adrenaline, glucagon and glucocorticoids. As a result, an unrecognised hypoglycaemic attack during sleep leads to hyperglycaemia before breakfast.

It is essential to appreciate this possibility to avoid the mistake of increasing (rather than reducing) the evening dose of insulin in this situation.

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