This is currently in a category of cures that are always a decade away. I am happy that the researchers are putting it out there to attract interest and investment, but the GRI-type insulins remained in lab settings for about 30 years now and it is somewhat troubling to not see progression into and through the stages of pharma clinical trials on T1D patients.
Clearly, there is tremendous potential to make money here – diabetes is a very serious epidemic worldwide. So why hasn't this progressed out of the lab?
I was curious about this myself so I looked up a bit more about this. Here's what I found;
>Even though there have been many publications and patents on the subject, no mechanism has yet been shown to be compelling enough to treat diabetes.[1]
>An apparent more effective strategy is to give insulin glucose-responsive properties that let it respond to glucose reversibly. Merck created a system ... because of its incredibly low efficacy, this system did not merit advancement past phase I clinical trials.[1]
It sounds like they're saying basically that they exist, but aren't yet effective enough to replace the old standard. This particular design is newer.
From the study linked in the article as citation 1:
>Here we report the design and properties of NNC2215, an insulin conjugate with bioactivity that is reversibly responsive to a glucose range relevant for diabetes, as demonstrated in vitro and in vivo. NNC2215 was engineered by conjugating a glucose-binding macrocycle and a glucoside to insulin, thereby introducing a switch that can open and close in response to glucose and thereby equilibrate insulin between active and less-active conformations.
Essentially it's a new attempt at making a GRI that's more promising. It's insulin attached to a molecule that binds to insulin to block it from working unless glucose is present, in which case it binds to glucose instead and allows the insulin to be active. Of course that also means it will need to go through full FDA approval process which would keep it about ten years away if it does really end up being effective enough.
But this time could be different! It's very cool conceptually too. The fact that it's possible to make a drug that works like that. It's amazing to see these novel drug delivery concepts develop in real time.
It's always a decade away because the progress promised shows up, and it improves quality of life a bit, but isn't enough and is very expensive.
We've gotten a variety of synthetic insulins with different rates that help control the disease. We've gotten pumps and meters and very cautious closed-loop feedback.
Now, an insulin itself that adjusts its potency based on blood sugar. We'll get that in the next decade or a bit more. But it'll be very expensive and it will be a relatively ineffective control mechanism-- making control a little bit easier for diabetics and blunting worst case episodes a bit.
I agree that many types of treatments have been advancing. Closed loop is a good example, and stem cell-based islet transplants are in real clinical trials now. We have gotten synthetic insulins that act much faster like Fiasp and stuff like Tresiba that's a multi-day action time prolonged insulin. GLP1 inhibitors are more commonly available for T1Ds, especially now that they are in weight loss drugs that doctors are starting to more easily prescribe off-label to T1s. Metformin has basically become on-label for T1Ds due to its benefits to insulin sensitivity. But the smart insulin hasn't made much progress for the last several decades.
I'm not saying it's all doom and gloom. I'm bringing attention to different rates these things evolve at and questioning why GRIs haven't left the lab since the 90s. :)
The molecular GRI work in the 90s was really proof of concept work that showed you could maybe build something like this, not something that looked a decade from approval. From what I remember, the early work spun off free radicals, had the middle of its set-point in the wrong place, and its "gain" was minimal.
Clearly, there is tremendous potential to make money here – diabetes is a very serious epidemic worldwide. So why hasn't this progressed out of the lab?