Advanced treatment and technologies for diabetes at day four of international diabetes conference.

And here we are…the last day of the ATTD conference already! And it’s been a good one…not in Paris, granted, but good nonetheless!

Telehealth and digital approaches to diabetic treatment

Professor Simon Heller from Sheffield, a leading figure in diabetes structured education, introduced the session on improving adherence and reducing burden. First, Cincinnati’s Susana Hatton spoke about an intervention for addressing fear of hypos among parents of children with type 1 diabetes. REDChIP (Reducing Emotional Distress for Childhood hypoglycaemia In Parents) is a cognitive behavioural therapy delivered direct to home video, which aims to reach those in rural areas in Kansas and Missouri. A pilot trial showed the successful reduction of fear with the intervention, as well as a reduction both in parental stress and diabetes distress, as well as in the child’s HbA1c. “Given that telehealth is our new normal, this is a great opportunity to advance behavioural treatment for children with type 1 diabetes,” she said. 

Then Korey Hood form Stanford University discussed leveraging telehealth and digital approaches to optimise use of devices. “Keep the focus upon the person with diabetes, not the device,” he advised. Barriers he’s discovered include scepticism and inertia and he believes these can be dealt with by showing how others have successfully started to use devices like continuous glucose monitoring (CGM).

His team is currently working on improving engagement on this issue through diabeteswise.org which helps people identify those devices that could be a good fit for their lifestyle. In a 2020 study, they found that after looking at the site, one quarter of participants went on to open up a discussion about adopting a new technology and 6% actually began to use it – mainly CGM – and that was within the first month, with numbers rising as the study progressed.  “Telehealth can do a lot of things, it can lead to a broader access to diabetes care which is something really important for us to do,” Korey concluded.

Simon Heller closed the session with a talk on his special subject. “It’s a failure in duty of care not to provide structured education,” he said. The latest meta-analysis shows that, overall, structured education leads to a relatively modest reduction of 0.38% in HbA1c. “So, I do think that we can say that structured patient education is absolutely of benefit – that reduction might not sound like much, but at the population level, it would reduce microvascular disease at least.”

Finally, what about virtual structured education of which there has been a lot over the last 12 months thanks to the ongoing COVID-19 pandemic? There have been many studies and Simon referred to one from University College London which showed no real difference between web-based and face-to-face structured education. He also noted that, in the UK, 50% of people with type 1 and 90% of those with type 2 are offered education but only a ‘disappointing’ 10% actually take up the offer. 

Looking at developments in oral and smart insulin

An ATTD meeting would not be complete without a session on oral insulin, particularly in this centenary year of the discovery of insulin. Hans de Vries from Amsterdam opened with a discussion of once-weekly insulins, which all depend upon a subcutaneous depot formulation, with different companies having different approaches. There is the Eli Lilly version (BIF), now into Phase 2 clinical testing, and Novo Nordisk’s Icodec which has three amino acid substitutions in the insulin molecule. In a recent trial of Icodec against insulin glargine, HbA1c was similar and Time in Range slightly better with Icodec, and other trials are underway. “The once weekly insulin is more convenient for patients, so you will see less therapeutic inertia with them,” he noted. 

Another exciting development is the development of smart insulins, as discussed by Germany’s Tim Heise, who began by warning that it will be a long time before these will be seen in the clinic. So why are smart insulins so challenging to develop? The principle is relatively easy – you just attach glucose to a glucose- sensing moiety, and when glucose levels are high, this binding releases the insulin and when levels drop, it grabs the insulin back. This idea was first described 40 years ago but, thus far, there has been only one human trial, despite many ideas being explored.

Tim gave an excellent review of the smart insulin field, including microneedles and nanoparticles containing glucose oxidase as a glucose sensor, which have shown promising results in animal tests. He concluded that the glucose-sensing aspect works, but there is still some toxicity from the enzyme and some issues with speed of response to glucose changes. The latest development is a potentially faster responding system using an insulin-carbohydrate conjugate, which has been tested in both minipigs and in humans. “Overall, this was not as successful as many hoped it would be, but it was the first human study with a glucose-responsive insulin. We certainly don’t have all the answers yet, but we are really learning from experience from all over the world and there is hope that we will finally succeed,” Tim concluded.

Finally, Tim’s colleague, Eric Zijlstra discussed oral insulin, a project with a very long history, given that this research began soon after discovery of insulin itself 100 years ago! The first clinical trial around this time showed that oral insulin can lower blood glucose, but its effect is highly variable, and it has lower potency than injected insulin.

“Why do we keep on with oral insulin?” Eric asked. “Because patients obviously prefer it, and it has pharmacological advantages and behaves more like physiological insulin.”

The challenges are pH and enzymes in the digestive tract as well as poor absorption. So oral insulin technology relies on protecting the molecule and improving its absorption. Eric went on to review the three oral insulin candidates currently under development.

Biocon’s insulin tregopil IN-105 is being developed as a mealtime oral insulin for type 1 and type 2 diabetes and they are looking at how close to the meal it can be dosed and how this affects adherence and so on in a real-world setting. Oramed’s ORMD-0801 is being explored as a complement to injection in type 1 diabetes and in type 2 for bedtime and mealtime dosing, with promising results in a Phase 2 study. Finally, there is Novo Nordisk’s O1 338, the first basal oral insulin, which has undergone a Phase 2 trial against insulin glargine. Although it achieved glucose lowering comparable to glargine, as much as 50 times more oral insulin was needed to achieve this effect and Novo Nordisk has discontinued its development for this reason. So, although there are many trials ongoing, Tim is not confident that ATTD in five years’ time will be discussing a commercial oral insulin, although he still thinks that new delivery technologies could provide a bright future for this approach.

So let’s watch this space!

Further reports to follow – visit DRWF news page

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