Ultrafast insulin from Stanford slashes peak time to efficacy in pig diabetes models

Diabetes blood sugar testing
Scientists designed an ultra-rapid formulation of insulin, which reached peak activity in pigs with diabetes about twice as fast as a commercially available option. (Pixabay/stevepb)

Many rapid-acting insulin products are available, including Novo Nordisk’s NovoLog and Fiasp, and Eli Lilly’s Humalog. Still, people with diabetes need better options for controlling mealtime blood glucose levels with even faster rates of action.

Now, a Stanford University team has designed a new, ultrafast insulin formulation. It activates so quickly that it resembles how insulin naturally works in a person without diabetes, the researchers reported.

According to results published in Science Translational Medicine, the therapy, called UFAL, reached peak activity in pig models of diabetes in as little as nine minutes, about twice as fast as commercially available options.

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The researchers focused on so-called monomeric insulin. Compared with insulin dimers and hexamers, monomers are more rapidly absorbed into the bloodstream after injection. Problem is, monomeric insulin is very unstable, as it can aggregate in a way that can trigger an unwanted immune response.

“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,” Eric Appel, Ph.D., the study’s senior author, explained in a statement.

In vials, monomers are drawn to the surface of liquid, where they aggregate. So the Stanford scientists set out to find polymer vehicles that could serve as barriers between the insulin molecules and the liquid interface.

Among nearly 1,500 candidates, one polymer material emerged as a winner. While monomeric insulin on its own aggregates in about two hours, the polymer-based formulation remains stable for over 24 hours under stress. It did even better than commercial insulin, which typically stays stable for less than 10 hours.  

Then the team tested the formulation in diabetic pigs. UFAL reached 50% of peak after around five minutes, about 2.4-fold faster than Humalog did, the researchers reported. The novel treatment’s action time of nine minutes was far better than that of Humalog, which became active in about 25 minutes.

The polymer-delivered monomeric insulin formulation showed faster action than commercial rapid-acting insulin analogs. (J.L. Mann et al., Science Translational Medicine [2020])

In addition, the Stanford team used a pharmacokinetics model to predict the drugs’ performance in humans. The model shows a human UFAL time to onset of 2.5 minutes, peak exposure at 10 minutes and a duration of 28 minutes. In comparison, available fast-acting insulin analogs, such as Humalog, showed a time to onset of 14 minutes, a peak at 43 minutes and a duration of 157 minutes. The more rapid start and finish of activity could make it easier for people to manage their mealtime blood sugar levels, the researchers said.

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The diabetes community isn’t exactly satisfied with existing fast-acting insulin injections, with some patients arguing they're still not fast enough. The Stanford team hopes the polymer-based UFAL could ultimately offer a better option to improve diabetes management and reduce patient burden.

Additional preclinical studies are needed, but the researchers plan to start testing their products in humans soon after, they said. It’s possible the formulation could also be incorporated into an artificial pancreas device that functions without the need for human intervention, they added.

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