Painless Progress: Exploring the Future of Non-Invasive Insulin Delivery for Diabetes (2023)

Painful and frequent insulin injections have always been a significant issue for people with diabetes.

However, thanks to advancements in non-invasive insulin delivery methods, diabetes care has become more accessible, more convenient, and pain-free.

In this article, we’ll explore the different non-invasive methods of delivering insulin that you can try instead of traditional syringes.

Insulin delivery refers to different drug delivery methods that help your insulin doses reach their target areas for absorption.

For example, transdermal insulin delivery helps insulin pass through the skin into the subcutaneous layer, which gets absorbed into the blood. Once there, the insulin regulates your blood sugar levels by burning excess glucose for energy.

There are several methods of insulin administration and delivery, each with its unique set of pros and cons. However, they can be generally classified into two classes: invasive and non-invasive insulin delivery systems.

Invasive insulin delivery methods are those that rely on piercing or penetrating the skin for the delivery of insulin. 

This includes the following:

• Traditional insulin injections

• Insulin pumps

• CGMs (continuous glucose monitoring devices)

• Insulin pens.

Invasive insulin delivery methods have several disadvantages that have pushed diabetics to look for non-invasive alternatives.

Here are a few common issues encountered by diabetics:

• Pain: Insulin injections, such as traditional syringes or insulin pens, can be painful, especially for children and adults with low body fat.

• Needle Phobia: Two in three children and one in four adults have some kind of needle phobia, which often results in poor patient compliance.

• Reactions: Users often experience redness and swelling in their injection sites. These symptoms are most common when you first start taking insulin.

• Lipohypertrophy: Repeated injections of insulin into the same area may lead to fat deposits (lipohypertrophy). This can affect insulin absorption, often leading to hypoglycemia (low blood sugar).

• Infection: Improper injection technique or contamination of the injection site can lead to bacterial or fungal infections. This is especially common with insulin pumps and CGMs.

• Skin thickening: Repeated injections into the same area can cause skin thickening. This makes it harder to insert the needle and increases the risk of intramuscular injections instead of subcutaneous insulin injections.

With non-invasive insulin delivery methods, the skin remains intact without being pierced or penetrated. It’s a more favourable method of administration, especially for people with needle phobia.

There are several methods of non-invasive insulin delivery, including the following:

• Oral insulin delivery

• Inhaled insulin delivery

• Transdermal delivery

• Jet injectors (Needle-free injection devices)

Each of these methods has its unique set of pros and cons. However, jet injectors, such as InsuJet, are the most popular, convenient, and easy to use.

Jet injectors are the most popular non-invasive insulin delivery method because of their simplicity, precision, and convenience. They are especially popular with patients who have needle phobia because jet injectors use needle-free injection technology.

Most jet injectors have three main components:

• A pen-like delivery device with a button for injecting insulin

• A disposable injector nozzle

• A disposable adaptor that holds the insulin cartridge or vial

A jet injector, such as InsuJet, uses a spring-loaded mechanism to create high pressure that turns your insulin doses into a fine jet stream. This jet stream of insulin passes through the pores of your skin instead of penetrating the skin layers as a syringe would.

In the case of InsuJet, the diameter of the jet stream is about 150 μm, which is less than the thickness of two sheets of regular paper. This minimal diameter helps the insulin dose pass through your skin virtually pain-free.

The high pressure is designed to propel the insulin molecules deep enough into the skin layers to reach the subcutaneous layer and start dispersing immediately.

Normally, insulin administered using a hypodermic needle stays in one spot and gets absorbed over time. However, with a jet injector, the dispersed molecules cover a larger surface area, which results in faster absorption and onset.

Faster absorption leads to better glycemic control and prevents spikes in blood sugar. This is especially useful for diabetics who have difficulty controlling their blood sugar after meals.

For example, studies showed that insulin administered by InsuJet was absorbed 40% faster than that administered using regular syringes. It can lower your post-meal blood sugar up to 45 minutes faster than traditional syringe-administer insulin.

• Painless: Insulin jet injectors are pain-free because the jet stream of insulin produced has a much smaller diameter than that of hypodermic needles.

• Easy to Use: Jet injectors are easier to hold and use than traditional syringes, especially since you don’t need to draw insulin from a vial or measure a dose.

• Faster Onset: Jet injectors offer faster insulin absorption, which means faster onset of action and better glycemic control at mealtimes.

• Anxiety-free: Jet injectors are a great anxiety-free alternative to syringes, especially for diabetics who have needle phobia.

• More Accurate Doses: Jet injectors have buttons and dials that allow you to set the dose automatically without doing calculations, drawing insulin, or reading small prints on the side of a syringe.

• Safety Mechanisms: Some jet injectors, such as InsuJet, come with a locking safety mechanism that stops the insulin from being accidentally injected into the air. It only releases the dose when you press a certain button while pressed against the skin.

• Initial Cost: Jet injectors have a higher initial cost than traditional syringes, but they can save you more money in the long term.

• Training: Some jet injectors require training before you can use them, although the most recent ones, such as InsuJet, are extremely intuitive.

Another non-invasive method of taking insulin is transdermal drug delivery. The most popular transdermal method is insulin patches.

Transdermal insulin patches are tiny patches that contain a controlled-release form of insulin. They are attached to the skin, much like a nicotine patch, and the insulin passes through the skin into the subcutaneous layers for absorption.

There are generally two types of insulin patches:

• Bolus Insulin Patches: This type of transdermal patch releases bolus doses of insulin at mealtimes to help control postprandial blood glucose.

• Basal Insulin Patches: These patches offer slow, controlled insulin release over 24 hours or more, mimicking your pancreas’s natural basal insulin.

Although there are several working prototypes of insulin patches currently under development, they still haven’t been made available to the masses. The main problem is the size of the insulin molecules, which must be extremely small to pass through the skin for absorption.

Also, since patches don’t have a spring-loaded mechanism like jet injectors, the insulin molecules have difficulty passing through skin pores.

• Discreet: Insulin patches are small and discreet. They can be hidden under your clothes and don’t need tubes or wires, unlike insulin pumps.

• Both Types of Insulin: Different patches offer bolus and basal insulin doses, giving you more control over your blood sugar.

• Painless: Patches offer a painless, non-invasive alternative to syringes and other methods that puncture the skin.

• Potential for Error: If you use multiple patches or forget to remove an insulin patch, you might experience hypoglycemia.

• Dosing Limitations: You can’t adjust the dose inside an insulin patch. It comes with a preset amount of insulin intended for some time.

• Limited Availability: Transdermal insulin patches are still under development and are unavailable in many regions and countries.

Almost every diabetic who’s been told they need to take insulin injections has asked if they can take a non-invasive method like a pill or tablet instead.

However, oral insulin pills are still under drug development and aren’t readily available to the masses.

The main problem with the oral delivery of insulin is that insulin is a hormone, meaning it’s made of protein. If you were to take insulin orally, it would be destroyed by the acids and enzymes in your stomach and gastrointestinal tract almost immediately.

There have been some attempts to create an acid-resistant insulin for oral administration. However, there was still another problem to be considered: the effect of food and drinks on the insulin absorption rate.

Also, different people have different metabolism rates, which makes it difficult to determine just how much insulin will be absorbed and how much will be metabolized.

Overall, there’s still much research and development before oral insulin pills get FDA approval for diabetes mellitus.

• Convenience: Oral insulin pills can be taken anytime without the need for injections, syringes, vials, or cartridges. This makes it easier for patients with difficulty administering injections or needle phobia.

• Portability: You can easily take your oral insulin pills with you anywhere you go, and they won’t be affected by your daily activities, unlike insulin pumps, for example.

• Easy Dosing: You don’t need to calculate your insulin doses or draw insulin from a vial.

• More Compliance: Patients are much more likely to stick to their insulin regimens with pills than invasive insulin delivery methods such as syringes.

• Limited Availability: Oral insulin pills aren’t readily available.

• Variable Absorption: The rate and extent of absorption for oral insulin pills varies depending on factors like food intake, stomach emptying, and individual metabolism.

• Gastric Side Effects: Common side effects of oral insulin pills include nausea, vomiting, or abdominal pain, especially at the start of treatment.

• Slower Onset of Action: Oral insulin works much slower than other forms of insulin, which gives you less control over your blood glucose levels.

• Risk of Drug Interactions: Certain medications, such as antacids or acid-reducing drugs, can interfere with the absorption of oral insulin pills.

Inhaled human insulin is another non-invasive insulin therapy that has recently gained traction.

Diabetics who take inhaled human insulin treatment use an inhaler to breathe in tiny insulin particles. This micronized insulin powder travels through the airway until it reaches the lungs and dissolves.

Next, the insulin gets absorbed from the lungs into the bloodstream. The process is very similar to using an asthma inhaler, but instead of a drug that helps you breathe better, the insulin helps regulate your blood sugar levels.

There have been several FDA-approved insulin inhalers over the years, with the latest being Afrezza. However, people with diabetes haven’t been particularly fond of this insulin formulation, and it’s not quite as popular as other non-invasive methods.

One major problem with inhaled insulin is that it only works with short or rapid-acting insulin. There aren’t any intermediate or long-acting inhaled insulin formulations.

This means inhaled insulin can only regulate your blood sugar at mealtime, replacing your bolus insulin injections. You still need to take some form of basal insulin to keep your blood glucose steady throughout the day and as you sleep.

• Fewer Injections: Inhaled insulin replaces your bolus insulin injections, allowing for fewer pinpricks throughout the day.

• Easy Storage: Inhaled insulin comes in the form of dry, micronized powder, which makes it easy to store anywhere without a refrigerator.

• Less Anxiety: Inhaled insulin causes less anxiety for diabetics with needle phobia, resulting in better patient compliance.

• Discrete: Inhaled insulin can be carried and administered discreetly, unlike traditional invasive delivery methods.

• Dosage Control: It can be difficult to control inhaled insulin doses since the absorbed dose depends on the patient’s breathing technique. This can result in uncontrolled blood sugar.

• Adverse Effects: Inhaled insulin can cause respiratory problems, such as bronchospasms, coughing, and shortness of breath, especially in patients with pre-existing lung conditions.

• Expensive: Inhaled insulin is typically more expensive than traditional syringes and insulin vials due to limited availability.

• No Basal Inhaled Insulin: There’s no form of inhaled basal insulin for keeping your blood sugar levels steady throughout the day.

While traditional syringes are still popular in some regions, more and more people are making the switch to non-invasive insulin delivery methods.

They offer a more convenient and pain-free method of controlling your blood sugar and your diabetes.