'Smart' insulin prevents diabetic highs – and deadly lows

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.

>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.

[1] https://www.insideprecisionmedicine.com/topics/translational...

I'm optimistic about the VX-264 approach of islet cell encapsulation. Even if the encapsulation eventually breaks down, using stem cell derived cells (rather than cadaver pancreata) means you could simply replace the implant after a few years.

Maybe one day it could be made into a infrequent injection? Like if you just had to get a shot from your doctor every few months, perhaps that would be easier patient compliance. There was some new hiv preventative that recently demonstrated something like that, I wonder if the technique could be repurposed or not.

[1] - https://www.nature.com/articles/s41573-020-00092-2