Injection of “smart insulin” regulates blood glucose levels for one week
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After the failure of SmartCells "smart insulin" in 2018 I look at such claims very skeptically. The source paper is Pay Per View but the Supplementary Information tells me all I need to know. In the SI for Figures 1-13 document if you look at Figure 2f and its caption you'll see the pharmacodynamic results in mouse. In a nutshell, their "smart insulin" lowered plasma glucose levels by a statistically significant medically insignificant degree, the difference between groups was on the order of 5-10 mg/dL. At 10 minutes, 2 and 4 hours the insulin treated group had lower blood glucose than did the smart-insulin group. By 4-6 hours the blood glucose levels of both groups were back to baseline. Hardly a once a week drug. Figure 9, showing data for diabetic minipigs is perplexing and appears to show that one pig treated with smart insulin was healthier than the single control pig. The other treated pig showed a modest but highly variable improvement in blood glucose levels. This paper reminds me of the Smartcells debacle - the idea worked in animals but failed in humans.
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In 2040, someone will make a very minor change to the formula, all the doctors will tell their patients to switch to the new formula, and there will be no demand for the old formula by the time it hits generic status. Nobody will produce the generic due to lack of demand.
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If you do not have access to the whole article, then you miss important details. That figure is referring to the activity of the modified insulin analogue, but it is not bound to the phenylboronic acid (PBA) derivative that acts as the glucose responsive insulin releasing mechanism.
Therefore, that figure is showing a good thing in that their modified insulin still has the properties of naturally produced insulin.
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Technically not really "generic". It's still manufactured by Novo Nordisk under a special contract with Walmart, and is only available through Walmart, not advertised or mentioned by doctors, and insurance doesn't pay for it so if you have insurance you'd only go for it if it's cheaper than the co-pay for other brands with your insurance, which it was for me. And if you're like me and need 4 to 5 vials per months, it's still pretty damn expensive.
I finally discovered Eli Lilly has a savings card for uninsured patients to make a month's supply (of any amount) only $35 for their brand. (Though it has an annual limit, so past a certain amount per month you'd exceed that.)
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I already learned this the hard way. After I was diagnosed with adult onsite type 1, I was put on twice daily insulin shots along with a meal plan that limited sugars. Between them, they controlled my diabetes very effectively. I tested 3 or 4 times a day and every time, my sugar was in a desirable range of 100-160. For the first few years it was perfect and of course I gradually tested less often, until I was hardly testing at all. That is of course when my diabetes got out of control. By the time I was put on sliding scale, my A1C was 11. Now, keeping it under control requires about 10-11 shots a day, and I have a continuous glucose monitor (GCM), backed up by regular test strips.
This insulin has the potential to be a big deal for me, assuming our insurance overlords will allow it. But I will keep the GCM and testing regimen, because I have seen this movie before.
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$35 for a vial of Lantus (cash) in 2003. $750 for that exact same vial in 2018.
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Because of my diabetes, I always get the best PPO insurance option my employer offers. Much better than most. That didn't stop me from getting whacked with a $300 copay on Lantus insulin - insulin that I paid $35 in cash for 20 years ago.
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For something like this where you don't even need to dose the insulin based on blood tests, the temptation to just not test at all should make a GCM mandatory unless you can't reliably use one.
Sadly, I know insurance doesn't always like to cover GCM's even though they are pretty much superior to test strips for the active management. Seems like a lot of very expensive diabetes complications could be avoided if they were available to everyone.
One hopes that it won't be the same with smart insulin whenever we figure it out.
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My daughter-in-law wears a patch-monitor that monitors her blood levels all the time and alerts her (and my son's) phones whenever her levels drop. She doesn't have to monitor it herself any longer. Science and tech, it is great.
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comments by Americans about insulin's price and their so-called..."insurance" create, in me, a near-panic state.
To me, it's living in hellish land if health can be so expensive and out of hands for millions of citizens of the same country than people writing comments in that website. It's a blatant lacks of considerations for others people, a crazy individualistic way of life.
It's out of question, at the point of participating in riots, refusing to vote and any means, my own country devolves its healthcare system to the point of the USA.
no, no and NO !
To me, it's living in hellish land if health can be so expensive and out of hands for millions of citizens of the same country than people writing comments in that website. It's a blatant lacks of considerations for others people, a crazy individualistic way of life.
It's out of question, at the point of participating in riots, refusing to vote and any means, my own country devolves its healthcare system to the point of the USA.
no, no and NO !
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As a physician currently working in a low socioeconomic area this is the real question. (That it was so utterly downvoted indicates how inconvenient and frustrating this truism is. Everybody is TIRED of hearing this and feels powerless to change it.)
The impact, novelty and technical sophistication of this approach is wonderful and I hope it works out but people are still dying earlier, going blind, stroking, and having legs amputated. One 31 year old patient that has lost his ability to speak from a stroke is not 25 feet from me as I type this. He has had Type 1 Diabetes since age 8 and has known an unenviable life. Socially and politically we need to stop bickering and rally behind pragmatic steps to improve access to health care and accelerate the research pipeline to land these new biotech innovations into the lives of ALL people. We need strong democratic means of advancing these. I left translational research because of the sheer impossibility of insurance eventually paying for the treatments we developed. Part of my idealism died there. Despite demonstrable social good, those that make profits do not care about the sick and disabled. The wealth extraction vehicle known as healthcare needs a whole recasting.
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Well,, I was tempted, but since my investment in Luna, the bank owns the house, and the kids.
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Shouldn't be, but I'm quite certain it'll be priced like it comes in platinum vials coated in diamonds in the US.
![:\](https://cdn.arstechnica.net/civis/data/assets/smilies/slash-1x.png "Slash :\")
I think a cure will happen, but probably not in our lifetimes. Someday, though. Maybe our great-great-grandkids will see a cure for diabetes come around.
Also don't forget environmental hazards, such as all the soldiers in the Vietnam war that got Agent Orange dumped on them. (Also people handling it in the Air Force and plenty of others.) My dad's one of them, and despite eating healthy and having an active lifestyle, he developed type II diabetes thanks to it. At least the VA gives him some disability money each month for it, but he'd much prefer not being diabetic. The really frustrating part is there's nothing he can do to make it go away. People who develop type II diabetes due to obesity can lose weight and exercise, putting it into remission, but people impacted by chemicals can't, because it's damaged their body permanently.
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I've been Type 1 for 27 years and share your views...we've seen too many potential cures or treatments go nowhere, but pumps and CGM makes life so much better. I use Omnipod to avoid that tubing problem.
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I have to admit I’m a bit surprised and disappointed that diabetes treatment isn’t further along. I’m not diabetic (yet?). But I figured with glucose monitors attached to one’s arm, there’d be a better system in place to deliver insulin based on those glucose monitors already. I truly hope this system in this article leads to better treatment and management in the not-too-distant future!
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There are insulin pumps that dose based on the sensor. The difference is that with the smart insulin you don’t have to count carbs, calculate doses, deal with lows, and it should keep blood sugar levels more stable. Basically with smart insulin I wouldn’t be constantly stressed out trying to keep my blood sugar stable.
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I think you are a bit too optimistic here. One of the major issues is that Insulin has a delay before effectiveness and a long tail. Smart insulin dispersal doesn't know that you are just about to go on a long run or drive a car or do any number of activities where you need to make sure you don't go low. You know what you are going to do and can adjust your levels in advance, the smart insulin can't predict that.
I can see smart insulin being used as a basal and we still continue to use other tools for bolus.
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Expecting anything diabetes related to actually become a treatment anytime soon would be enough to be too optimistic. Yes, I know how insulin works, I’ve been a diabetic for almost 30 years. If it’s already inside the body and reacting directly to glucose levels it should prevent spikes vs having to inject 15+ minutes before eating to have any hope of my cgm graph for the day not look like a roller coaster. Lows from exercise will indeed be an issue but that’s something for them to figure out how to handle lows like that before releasing it.
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I think there are also one or two Vietnamese civilians who were affected. And they were not the ones dumping the stuff.
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From a societal perspective, diabetes induced disease and health factors is really expensive to handle so I’m sure both insurance companies and national health services would jump all over this if it works. I know I’d be first in line to try it.
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Yeah, there’s a reason NovoNordisk (the world’s biggest insulin producer) has a market cap larger than the GDP of country they’re based in (Denmark)…
That said, in my country all insulin and type 1 diabetes related treatments are fully subsidised, simply because it will cost more down the line from complications if patients aren’t properly treated now.
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Can we have the conversation early, where we decide to call this concept "responsive insulin" or something, not "smart insulin"? Even "[cliche] insulin" (including the brackets) would be a fun alternative.
Anyway, 5/5 for Beth's lack of sugarcoating here.
Anyway, 5/5 for Beth's lack of sugarcoating here.
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Why stop at Type 1? In theory, this product would also allow Type 2 patients to stop taking Metformin, Pioglitazone and injectibles that have so many cumulative side effects.
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This. My grandmother was diabetic and we had more than a few scares where she accidentally over-injected and crashed, or didn't properly account for the snack that she ate and spiked into the 400's. Or sometimes you get the "fool in the shower" effect where her sugar would drop, she'd eat one of her emergency snacks, her sugar would overshoot, then she'd over-inject, then need another snack. It was a vary fiddly, unreliable process that only got more difficult as she aged. We were fortunate that she never suffered any of the more severe consequence that can come from poor blood sugar regulation ... blindness, amputations, coma, death.
Fewer injections per week is convenient, but the real game changer is tighter sugar regulation from a more lenient and easier to manage dosage range. Lots of younger diabetics get more reliable control over their blood sugar levels by embedding an insulin pump inside their bodies, and this can be a game changer, but it's a complicated device that has to be surgically implanted, then still requires a non-trivial maintenance regime, including regular injections through the skin into the device to provide the device with fresh insulin, and nightly magnetic charging, etc. It would be liberating to achieve the same regulation effect from a single weekly injection, with no strings, wires, or tubes attached in between. It also stands a decent chance of being much cheaper, eventually if not immediately.
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While the insulin may not be any more intelligent than auto-balancing a single chemical concentration, it requires a lot of smarts, experiential wisdom, and constant vigilance for a human being to achieve the same outcome via monitoring their current blood sugar level, inspecting every food they consume, predicting the quantity and timing of it's impact, and judging how much insulin to add into the system at several points throughout the day. If it works as advertised, I have no problem with the "smart" adjective. It gets the point across and there's no risk of confusion with the sense of "smart" in smart-phone.
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I think most countries in the world have figured out that preemptively helping people with their health is a good thing.
As you say it saves healthcare cost in the long term, but keeps people productive and paying taxes.
I don't think the US would ever countenance such communism though.
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Our insulin pumps are external devices, injecting insulin via a canula we change every 3-7 days (in the case of Omnipod, you change the whole device every 3 days)
I don't know if any commercially available insulin pump which is embedded under the skin, there are a number of issues to overcome for that to be possible.
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Neither can the pancreas or regular insulin, and non-diabetics get along fine. Smart insulin just has to be as good as that.
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Perhaps I'm mistaken about how typical insulin pumps work. My grandmother never used one, and I'm not diabetic myself. I did once have a friend with an insulin pump and it seemed like it was under her skin, or that something was, but she wasn't the sort of friend who I would have seen without her clothes, so I never got a very good look at it.
I have heard that insulin pumps greatly simplify blood sugar control compared to the guesswork my grandmother accepted as normal. How true is that? Is it completely automatic and foolproof, or is there still fiddling required? How big of an improvement would it be to be able to not need a device at all? Would that be liberating or only a moderate improvement? I know compared to the guesswork shots, anything better regulated would have been a lot more comforting.
As a non-sequitor story, of all the times we had health scares with my grandmother, one of them was kinda funny. She was a big coffee drinker, and one day, she unexpectedly started going in and out of consciousness and becoming semi non-responsive. My family got really worried and called and said I might want to fly down and see her one last time because she wasn't doing so hot and they didn't know what was wrong. They literally thought she was going to die. Turns out one of the nurses had given her decaf coffee by mistake. She took it black, thick enough for the spoon to stand up. No sugar, obviously.
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Hey All, I’ve been a type 1 diabetic for 47 years in the US…yay. As others have more eloquently posted, it’s a dammed annoying disease. But there is worse. I use an insulting pump plus CGM in a closed loop and it works well enough. The biggest issue, as most other have posted, is cost. I’m using Lispro (generic) now as it’s only 25 for the prescription which for me is 4 vials/month. The pump supplies and CGM sensors are not cheap at 1,500 a quarter with insurance. Having said that though, once I meet my deductible the cost drops considerably. If you don’t make a lot, or your insurance is basic, it would be very difficult to afford that treatment approach. OK, you couldn’t afford it.
With regards to a cure, I too have stopped believing that will happen any time soon as my doctors said 47 years ago it would be 5 years, then 5 more years, etc. I still get told this…I just sigh. I have observed, though have no proof, that all items related to type 1 diabetes are a cash cow to subsidize other research or drug production. How else do you explain 700/vile cost? I can’t. And yes, I suppose it could be as simple as greed. The costs only came down for insulin when diabetes advocates squawked hard and loud, which is the only way anything happens these days.
On topic for this articles, this approach sounds reasonable but it is such early days. As others have posted, yet again, so many attempts at both medical and technology treatments have come and gone that it is hard to invest mentally in new attempts, especially when it’s 5 mice and 3 mini pigs, which I didn’t even know was a thing! But like many breakthroughs, one day it’s not and then it is, so maybe this will pan out downstream.
With regards to a cure, I too have stopped believing that will happen any time soon as my doctors said 47 years ago it would be 5 years, then 5 more years, etc. I still get told this…I just sigh. I have observed, though have no proof, that all items related to type 1 diabetes are a cash cow to subsidize other research or drug production. How else do you explain 700/vile cost? I can’t. And yes, I suppose it could be as simple as greed. The costs only came down for insulin when diabetes advocates squawked hard and loud, which is the only way anything happens these days.
On topic for this articles, this approach sounds reasonable but it is such early days. As others have posted, yet again, so many attempts at both medical and technology treatments have come and gone that it is hard to invest mentally in new attempts, especially when it’s 5 mice and 3 mini pigs, which I didn’t even know was a thing! But like many breakthroughs, one day it’s not and then it is, so maybe this will pan out downstream.
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Yes, you are mistaken about how pumps work...it is a small cannula embedded in your skin (this is changed regularly), the actual pump is external. Just the pump by itself doesn't simplify any guesswork, and nothing is foolproof or automatic. As audincli9 notes above, there are quite recently introduced (and expensive) limited options for closed-loop control, but it sure isn't foolproof or automatic in the way you are implying.
The real benefit to the pump is to provide a consistent basal rate, along with the ability to much more easily manage boluses for meals and corrections (I was taking 10+ shots per day before going to the pump). The CGM is as much of a game changer, allowing instant read and trending of your blood sugar, along with alarms, without poking your finger and smearing the blood on a strip.
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Thanks, sounds like this weekly shot is a pretty big improvement. I hope they can develop it.
As annoying as diabetes management is now, it gets worse if you get to the point where you keep forgetting your keys and your kids have to convince you that maybe you shouldn't be driving yourself around anymore due to that whole missing the intersection thing (could she not see it, or was there a cognitive element? good thing it was empty). I mean, I'm already forgetful right now, and I'm glad I don't have diabetes because it's not a good disease for forgetful people.
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I checked the article for information on the polymer used to hold the insulin and the glucose. A poly lysine backbone with pendant 4-fluorophenyl boronic acids. More information on poly lysines here: https://pubmed.ncbi.nlm.nih.gov/34519501/ with links to lots more drug delivery research
The glucose will bind to the boronic acid groups irreversibly so once they are used up, a new dose is required. A lot of work is involved to find the optimal loading of the polymer with binding sites without adversely affecting insulin loading or solubility in the bloodstream.
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How would stop taking Metformin work? My body produces plenty of insulin, and the right amount. I need Metformin so it does its job, and stay away from sugar.
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By definition, your body does not produce enough insulin to match the lower efficiency that has developed. As a Type-1, I don't see how this wouldn't also help Type-2, assuming it ever actually works.
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With multiple type 1 family members, including me I like the idea of fewer injections and better regulation. I'm probably not going to like the co-pay when it hit the market. But I'm already salty after "affordable Insulin" tripled our co-pays for Humalog.
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