3 ms·

'Smart' insulin prevents diabetic highs – and deadly lows

119 points by gmays 2y ago

grahar64 2y ago
IMHO: This is the closest thing to a "cure" coming out in the next decade. Like a couple injections a day, wearing a CGM to make sure it is working, no calculations, no worry about carb intake. A lot of the other "cures" involve immunosuppressants which have a ton of bad side effects that can be worse than diabetes.
- cperciva 2y ago
  A lot of the other "cures" involve immunosuppressants 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.
- deleted 2y ago
  [deleted]
- dgoldstein0 2y ago
  "cure" is quite a strong term for something that has to be taken ever day. Even a once a day pill requires a nontrivial patient effort to consistently self administer. Far better than today's manual monitoring of blood sugar to be fair, but we still have to worry about people missing doses and continuing to refill and keep taking such a prescription. 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.
- rincebrain 2y ago
  I'd be interested to see if you can do something like [1] and then native stem cell derived islets, no isolation required... [1] - https://www.nature.com/articles/s41573-020-00092-2 https://www.nature.com/articles/s41573-020-00092-2
rubymancer 2y ago
T1 here. I couldn't read this, even with archive.ph. Here's a more accessible source: https://www.theguardian.com/society/article/2024/aug/11/scientists-hail-smart-insulin-responds-changing-blood-sugar-levels-real-time-diabetes?CMP=Share_AndroidApp_Other https://www.theguardian.com/society/article/2024/aug/11/scie... Reddit thread: https://www.reddit.com/r/diabetes_t1/comments/1eppvf5/scientists_hail_smart_insulin_that_responds_to/ https://www.reddit.com/r/diabetes_t1/comments/1eppvf5/scient...
- deleted 2y ago
  [deleted]
- joecool1029 2y ago
  Isn't this direct link to pdf? https://www.nature.com/articles/s41586-024-08042-3.pdf https://www.nature.com/articles/s41586-024-08042-3.pdf
- bsmartt 2y ago
  damn this reddit thread is 3 months old? t1 here as well, and i struggle pretty bad. having been t1 for 20 years or more, i just can't click every article my friends and family send me promising progress for diabetics or potential cures. its just not worth getting my hopes up even when its a reputable outlet making some extraordinary claims. this sounds really promising but yea. its also depressing. its kinda too late to save me even if this comes very soon. which i doubt it will. However, this so called 'smart insulin' sounds to me much more like the shit produced by non-diabetics pancreases. like theres just no way the non-diabetic body is making a hormone that doesnt fully kick in for 90 minutes. that just wouldnt be as resilient and effective as what i witness in the people around me. its insane how they can, for example, eat a tub of ice cream on a whim and not be blasted into the 400s. or just go wild exercising at length on an empty stomach and not have an emergency low sugar.
  - haccount 2y ago
    It kick in slowly because standard administration is subcutaneous which isn't a very well vascularized tissue. If you shoot up in your veins or into something more vascular you would have faster onset.
benrawk 2y ago
Doesn’t GLP1 do something similar?
- cperciva 2y ago
  No. Completely unrelated.
caseyy 2y ago
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?
- mlyle 2y ago
  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.
  - caseyy 2y ago
    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. :)
    - mlyle 2y ago
      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.
deleted 2y ago
[deleted]
sluz 2y ago
We’re about to see a Cambrian Explosion of novel compounds like this. It’s about to be a wild time on the Rx side of things.

119 points by gmays 2y ago

IMHO: This is the closest thing to a "cure" coming out in the next decade. Like a couple injections a day, wearing a CGM to make sure it is working, no calculations, no worry about carb intake. A lot of the other "cures" involve immunosuppressants which have a ton of bad side effects that can be worse than diabetes.

cperciva 2y ago
A lot of the other "cures" involve immunosuppressants 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.
deleted 2y ago
[deleted]
dgoldstein0 2y ago
"cure" is quite a strong term for something that has to be taken ever day. Even a once a day pill requires a nontrivial patient effort to consistently self administer. Far better than today's manual monitoring of blood sugar to be fair, but we still have to worry about people missing doses and continuing to refill and keep taking such a prescription. 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.
rincebrain 2y ago
I'd be interested to see if you can do something like [1] and then native stem cell derived islets, no isolation required... [1] - https://www.nature.com/articles/s41573-020-00092-2 https://www.nature.com/articles/s41573-020-00092-2

rubymancer 2y ago

T1 here. I couldn't read this, even with archive.ph. Here's a more accessible source: https://www.theguardian.com/society/article/2024/aug/11/scientists-hail-smart-insulin-responds-changing-blood-sugar-levels-real-time-diabetes?CMP=Share_AndroidApp_Other https://www.theguardian.com/society/article/2024/aug/11/scie... Reddit thread: https://www.reddit.com/r/diabetes_t1/comments/1eppvf5/scientists_hail_smart_insulin_that_responds_to/ https://www.reddit.com/r/diabetes_t1/comments/1eppvf5/scient...

deleted 2y ago
[deleted]
joecool1029 2y ago
Isn't this direct link to pdf? https://www.nature.com/articles/s41586-024-08042-3.pdf https://www.nature.com/articles/s41586-024-08042-3.pdf
bsmartt 2y ago
damn this reddit thread is 3 months old? t1 here as well, and i struggle pretty bad. having been t1 for 20 years or more, i just can't click every article my friends and family send me promising progress for diabetics or potential cures. its just not worth getting my hopes up even when its a reputable outlet making some extraordinary claims. this sounds really promising but yea. its also depressing. its kinda too late to save me even if this comes very soon. which i doubt it will. However, this so called 'smart insulin' sounds to me much more like the shit produced by non-diabetics pancreases. like theres just no way the non-diabetic body is making a hormone that doesnt fully kick in for 90 minutes. that just wouldnt be as resilient and effective as what i witness in the people around me. its insane how they can, for example, eat a tub of ice cream on a whim and not be blasted into the 400s. or just go wild exercising at length on an empty stomach and not have an emergency low sugar.
- haccount 2y ago
  It kick in slowly because standard administration is subcutaneous which isn't a very well vascularized tissue. If you shoot up in your veins or into something more vascular you would have faster onset.

benrawk 2y ago

Doesn’t GLP1 do something similar?

cperciva 2y ago
No. Completely unrelated.

caseyy 2y ago

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?

mlyle 2y ago
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.
- caseyy 2y ago
  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. :)
  - mlyle 2y ago
    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.

deleted 2y ago

[deleted]

sluz 2y ago

We’re about to see a Cambrian Explosion of novel compounds like this. It’s about to be a wild time on the Rx side of things.