Ultra-rapid insulin

Dr Paula Diab lists the wonders of the new advancement of ultra-rapid insulin and who would benefit from using it.

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To get a good understanding of what ultra-rapid insulin is and does, it’s best to get a broad overview first; and for that, we need to take a step back in time.

Early discoveries

Insulin was first discovered in the early 20^th century. Before then, diabetes was a fatal disease due to the inability to control blood glucose levels.

In 1921, a breakthrough occurred when Canadian scientist Frederick Banting, Charles Best, along with John Macleod and James Collip, successfully isolated insulin from the pancreas of dogs. This discovery earned Banting and Macleod the Nobel Prize in Physiology or Medicine in 1923. The first human patient was treated with insulin in 1922, transforming diabetes from a fatal diagnosis to a manageable condition.

Evolution of insulin types

Over the years, various types of insulins became available. Initially, porcine and bovine insulins were produced; these remained in use until about the 1980s. These insulins were extracted from the pancreases of pigs or cows and although effective, did sometimes cause allergic reactions due to slight differences from human insulin.

During the 1980s, recombinant DNA technology revolutionised insulin production, where scientists were able to reproduce human insulin in the laboratory. This reduced allergic reactions and improved efficacy.

Insulin analogues became available from the 1990s. These are synthetic insulins that have been genetically engineered to alter the structure of the hormone, allowing for improved pharmacokinetic properties compared to regular human insulin. These modifications help to better mimic the body’s natural insulin response, making them more effective in managing blood glucose levels in people with diabetes.

Duration of action of insulin

Apart from the different types of insulin, it can also be categorised according to its duration of action.

• Rapid-acting insulins: Insulin lispro, insulin aspart, and insulin glulisine all start working within 10 – 20 minutes, making them suitable for controlling blood glucose spikes during meals.
• Short-acting insulins: Regular human insulin remains in use in some countries for managing mealtime blood glucose and acts within 30 minutes. It can be particularly useful if you want a slightly delayed and extended response to the meal.
• Intermediate-acting insulins: Neutral protamine Hagedorn (NPH) insulin, introduced in the 1940s, acts within one to two hours and is sometimes still used for basal insulin needs, although it does still have peaks and doesn’t last the full 24 hours.
• Long-acting insulins: Long-acting analogues like insulin glargine and insulin detemir, introduced in the early 2000s, provide a steady insulin level over 24 hours, reducing the number of injections needed and providing much more predictable and reliable control than the old human insulin counterparts. This is the basis of insulin therapy for most people.
• Ultra-long-acting insulins: Newer ultra-long-acting insulins, such as insulin degludec, last up to 42 hours, offering even more flexibility and convenience.

Figure 1: Duration of action of insulins. (Insulin_short-intermediate-long_acting.png: Anne Peters, MDderivative work: M•Komorniczak -talk-, CC BY 3.0 https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons).

 

 

It’s important to note from Figure 1 that each insulin may peak at the time suggested but this may vary amongst individuals. It’s also important that many insulins still remain active within the body for some time and even short- and rapid-acting insulin may take six to 10 hours to be completely eliminated from the body.

Structure of insulin therapy

Long-acting insulin usually forms the basis of insulin therapy for most people. This will give a constant background amount of insulin throughout the entire day. In some cases, this dose may need to be given as a divided dose but generally it’s given as a single injection either in the morning or evening.

The purpose of long-acting insulin is controlling your fasting glucose levels (the first reading you take in the morning). Once these levels are stable and in range, you can begin to look at what additional medication may be required. This is where an individualised approach to diabetes management becomes so important.

The treating clinician will weight up the individual risk factors, various lifestyle constraints, and other practical influences to determine what is best recommended. These days there are many options, from oral therapy (drugs that fall into the classes of sulphonylureas, SGLT2 inhibitors, DPP4 inhibitors) to other types of injections (drugs that fall into the class of GLP1 agonists), or mealtime insulin.

Mealtime insulin

The purpose of mealtime insulin is to provide a balanced insulin response to the food that you eat at each meal. Very few of us, if any, eat exactly the same food for every meal, every day.

Mealtime insulin needs to be adjusted depending on multiple factors and given at a distinct time before the meal for it to work at its optimum. Ideally the calculation should include an assessment of the carbohydrates in the meal although the protein and fat content may also need to be considered.

The pre-meal glucose value is also important as is information on whether the glucose levels are rising or falling prior to the meal. There are many factors that influence this calculation but, in most cases, we tend to get away with a well-determined educated guess and adjust from there. Insulin pumps do a much better job of calculating this dose more accurately and giving more precise doses.

As opposed to the basal dose of long-acting insulin which is given once a day in the same dose every day, mealtime insulin is usually rapid- or short-acting insulin. These insulins have the ability to work much quicker within the body and provide insulin in response to the meal.

The main problem with rapid or short-acting insulin is that their response time is still slower than the time it takes for glucose to be absorbed from the meal. For this reason, clinicians often suggested taking insulin slightly before the meal to counter-act this delay but this is often not practical. Sometimes, the timing of the meal may not be accurate, such as in restaurants, the content of the food may not be known, or the person may not finish the entire meal, as often happens with children or the elderly. 

Ultra-rapid insulin: A game changer in diabetes management

The most recent development in the insulin family is the ultra-rapid insulins such as aspart and insulin lispro-aabc. These insulins start working in about two to five minutes, closely mimicking the body’s natural insulin response to meals. This rapid onset is achieved by adding ingredients that speed up absorption into the bloodstream. For instance, aspart includes vitamin B3 (niacinamide) and an amino acid (arginine), which enhances its speed of action.

What are the benefits of ultra-rapid insulin

1. Better post-meal blood glucose control

Ultra-rapid insulin works quickly enough to match the rapid rise in blood glucose levels that occurs after eating. This helps to keep blood glucose levels more stable and reduces post-meal spikes. 

2. Increased flexibility

Because it acts so quickly, ultra-rapid insulin can be taken right before or even just after a meal, offering more flexibility than traditional insulins which often require planning and pre-meal timing.

3. Enhanced convenience

For those with busy lifestyles, ultra-rapid insulin simplifies the management of blood glucose levels around meals, reducing the stress and complexity of diabetes care.

4. Potential for better overall control

By improving post-meal glucose control, ultra-rapid insulin can contribute to better overall diabetes management, potentially reducing the risk of long-term complications associated with high blood glucose levels.

Considerations and usage

While ultra-rapid insulin offers significant benefits, it’s important to use it under the guidance of a healthcare provider. There may be some people for whom an ultra-rapid insulin may not be the drug of choice. For example, an elderly person or someone who suffers from severe hypoglycaemia may prefer an insulin that is absorbed more slowly.

Additionally, young children may be adversely affected if an ultra-rapid insulin is given prior to the meal and they do not complete the meal. However, due to its quick mode of action, an ultra-rapid insulin may be a good choice to give to a young child after the meal. It may also not be an option for those who make use of pump therapy.

As always, discuss the advantages and disadvantages with your doctor and ensure that it is the right fit for your diabetes management plan. Your doctor or diabetes educator can also provide the necessary instructions on proper dosing and timing to ensure optimal blood glucose control.

Final thoughts

Ultra-rapid insulin represents an exciting advancement in diabetes care, offering quicker action and greater flexibility. If you’re finding it challenging to manage your blood glucose levels around meals, or if you desire more freedom in your daily routine, talk to your healthcare provider about whether ultra-rapid insulin could be a suitable option for you. As with any medical treatment, individualised care and professional guidance are key to achieving the best outcomes.

Living with diabetes involves constant management and adaptation, but innovations like ultra-rapid insulin provide new tools to help make life easier and healthier. Embrace these advancements and work with your healthcare team to optimise your diabetes management plan. And always remember that there is no best insulin, or even best medication for diabetes. Each drug we use is as individual as the people themselves who live with diabetes. Know the options available and discuss with your healthcare provider which is the best fit for your lifestyle and individual needs.

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