A new ultrafast insulin formula has been developed by a group of researchers. Their version was formulated to work up to four times faster than the standard formulation, and could be stable under stress for at least 24 hours.
The novel ultrafast insulin formula was developed by researchers at Stanford University, a private research university in the US. Their findings revealed that it performed far better than standard insulin formulas available commercially. Not only could work four times faster and more stable than standard formulas, but their formula could reach 90% of its peak activity in just five minutes. They published the results in the journal Science Translational Medicine.
Types of Insulin
Insulin is a hormone naturally produced by specific cells found in the pancreas. It is responsible for regulating the metabolism of certain nutrients, such as carbohydrates, fats, and protein, which in turn, helps balance the level of glucose or blood sugar. If insulin is low, glucose levels rise and can affect the normal functions of various organs. If insulin is high, glucose will drop and can induce serious complications to different organs. Thus, insulin levels must be balanced most times to prevent health conditions from arising.
According to the University of California – San Francisco, a public research university in the US, there are three main types of insulin formulas used for insulin replacement therapy. The differentiation of insulin types is based on action timing, maximal effect, and effect duration. This is one way to determine how effective an insulin formula in treating diabetes and similar metabolic conditions.
Fast-acting insulins are known for the onset of action between five minutes and one hour with a peak effect from one to four hours. These formulas can last for up to eight hours depending on the brand. Intermediate-acting insulins are absorbed slower than fast-acting formulas but last longer. These formulas have an onset of action from one to two hours, a peak effect of four to six hours, and a duration of at least 12 hours. And finally, long-acting insulins have the slowest absorption rate designed for a stable effect throughout the day. The onset of action is from one and a half to two hours with a duration of effect between 12 and 24 hours. These formulas tend to have a stable peak effect throughout their duration.
Insulin therapy is often used to treat diabetes. According to Statista, a German portal for statistics, the region with most diabetics in 2019 was Western Pacific at 163 million. It was followed by Southeast Asia with 88 million, Europe with 59 million, the Middle East and North Africa with 55 million, North America and the Caribbean with 48 million, South and Central America with 32 million, and Africa with 19 million.
Meanwhile, research data source Our World in Data revealed that the total number of deaths due to diabetes in 2017 was 1.37 million worldwide. The death rate among adults aged 70 years and older was the highest at 717,428. It was followed by 535,016 deaths among adults aged 50 to 69 years, 113,785 among people aged 15 to 49 years, 1,906 among children aged five to 14 years, and 1,714 among children younger than five years.
New Insulin Formula to Unlock Better Therapies
Historically, insulin therapy began in the 1920s when the hormone was found obtainable outside the human body. Beef and pork pancreases were the optimal sources at that time. Eventually, human insulin replaced those sources after its synthetic version could be grown in the labs. That formula mimicked the original insulin in the human body, though, it is grown using bacteria and yeast. The most recent formula called insulin analogs, a subtype of the synthetic human insulin, was derived from genetic alterations in the lab. Between human insulin and insulin analogs, the latter could provide a fast-action rate and deliver effects in a more uniform manner than the former.
At Stanford, researchers created a new formula with promising results. This formula could act quicker and last longer in the bloodstream, which could pave the way for better diabetes therapies. Their formula was a result of their focus on monomeric insulin or insulin with molecular structure theorized for fast onset of action, compared to other forms of insulin. But its use in medicine got stalled because of the structure's instability.
"The insulin molecules themselves are fine, so we wanted to develop a 'magic fairy dust' that you add into a vial that would help to fix the stability problem. People often focus on the therapeutic agents in a drug formulation but, by focusing only on the performance additives – parts that were once referred to as 'inactive ingredients' – we can achieve really big advancements in the overall efficacy of the drug," explained Eric Appel, senior author of the study and assistant professor of materials science and engineering at Stanford.
In the study, researchers highlighted that commercial insulins are formulated with a mix of three forms: monomers, dimers, and hexamers. The combination of the three forms has been intended to provide fast action with the least side effects. Among the three, monomers would be readily useful in the body. But inside vials, the molecules must be drawn to the surface of the liquid, where they could become inactive. This indicated the instability of monomers. Hexamers, on the other hand, expressed better stability than the other two but takes time before the body could break it down. So, they had to develop a custom polymer to balance the pros and cons of the three forms.
The formulation of the new insulin was centered around the polymers capable of interfacing and acting as a barrier to air and water, which would be critical to stability inside vials. As a barrier, the polymers should prevent insulin molecules to group together. To assist them, a robot in Australia helped them find candidates that yielded 1,500 potential polymer stabilizers. Next, each of the 1,500 candidates was analyzed and tested by hand to find the polymer with the best performance and least issues.
After hours of testing, they discovered the polymer stabilizer that could work with monomeric insulin. This stabilizer could increase the stability of insulin for a month, compared to the 10 hours of commercial insulins in accelerated aging tests. The stabilizer also maintained the stability of insulin for at least 24 hours under stress, compared to the one to two hours of monomeric insulin only. Because of these promising results, researchers received a seed grant to test the formulation in animal models.
Using diabetic pigs, they tested monomeric insulin with the polymer stabilizer. The insulin reached its 90% of peak effect in five minutes, quicker than the average 10-minute onset of action of fast-acting insulins. At 10 minutes, the novel formula reached its 100% peak activity, which was faster than the 25 minutes required by fast-acting insulins. In the human body, the onset of action and timing of peak activity of the new formula were equivalent to four times faster than commercial insulins.
The research team is now planning to apply to the Food and Drug Administration for approval. The approval will allow the team to test their formulation in human clinical trials. However, no clinical trials and no recruitment have been set by researchers at this time.