Diabetes developments – by Simon O’Neill

In a regular blog series, Simon O’Neill, Diabetes UK’s Director of Health Intelligence and Professional Liaison, rounds up the latest diabetes news.

This week Simon reports on the latest technologies, medicines and treatments.

Heat stable insulin?

A company called Thermalin has announced that they are working on the development of ultra-heat-stable, long- and rapid-acting insulins for patients with limited access to refrigeration.

Currently most insulins neeSimon-O'Neill-Director-of-Hd to be kept in a fridge between 2-8°C, though the vial or cartridge in use can be kept at temperatures up to about 30°C for a month. Insulin that freezes or reaches higher temperatures loses its potency and becomes unusable as the insulin gets “tangled” and can cause painful reactions when injected.

Although not normally a problem in the UK, even in June, other countries regularly experience temperatures over 30°C and in many developing countries local access to a fridge may be difficult.

The product that they are currently working on appears to be stable up to 46°C and for many months as well, meaning that it wouldn’t rely on refrigeration to continue to work. This is particularly useful, especially at a time when there is a huge growth in the number of cases of diabetes in tropical areas such as Africa, where diabetes is set to double in numbers in the next 25 years. It would also make transportation and distribution of insulin much easier, without needing a complicated refrigerated supply chain.

However, there is another potential benefit. Such ultra-stable insulins could also potentially enable an implantable, closed-loop pump, because the insulin could withstand body temperature for months without degrading. The company are also working on a 500 unit strength analogue insulin which would also mean that a micro pump could be used, requiring 1/5th the amount of insulin to achieve the same results.

They have already developed an intermediate-acting, ultra-stable insulin that has retained full potency after exposure to body temperature and agitation in an uncoated glass vial for more than one year so certainly a space to watch in future.

Metformin – the wonder drug?

Metformin has been used as a key drug in Type 2 diabetes (T2D) in the UK since the 1960s, though it wasn’t until the 1990s that it became more widely used in countries like the US. As the first drug of choice in the management of T2D, it is a cheap and very widely used generic but newer studies have shown that it may have a wider range of benefits.

Earlier this year a study in postmenopausal women with T2D showed that metformin may reduce the risk of dying from some cancers. The study evaluated 145,826 postmenopausal women between the ages of 50 and 79 who had regularly been taking metformin and found that the risk of dying from cancer was reduced, overall, compared to that seen in users of other medications. However, further studies will be needed to determine the long-term effect of metformin in cancer risk and survival from cancer.

Another study has shown that metformin may also be better for your heart than another commonly prescribed type of diabetes medication. An analysis of 204 studies involving 1.4 million people, suggested that metformin reduced the risk of dying from heart attack and stroke by about 30 to 40% compared with other commonly used drugs called sulfonylureas. Of course, other, newer drugs may also have strong cardiovascular protective factors such as pioglitazone, empagliflozin and liraglutide which have all recently been shown to offer protection.

A study looking at data over 13 years also showed that, for people with T2D on insulin, the addition of metformin is beneficial. Those on both insulin and metformin were at a significant 40% reduced risk for death and a significant 25% reduced risk for major adverse cardiac events compared with those treated with only insulin.

Finally, metformin is also being used in the autoimmune diabetes Accelerator Prevention Trial (adAPT). This is a study looking at children who have been identified as genetically at high risk of Type 1 diabetes (T1D) in Scotland. Children in the trial will be given either metformin or a placebo (dummy drug) to see whether metformin can reduce the rate at which insulin producing cells are destroyed by the immune system, which could delay or potentially prevent the onset of T1D

Between pump and injections

Johnson & Johnson have announced that their “OneTouch Via” device will be launched in the US by late 2016 with wider distribution next year.

The OneTouch Via is a very slim, plastic device worn on the skin for up to three days. It can hold up to 200 units of fast-acting insulin and allows the wearer to take insulin boluses, in 2 unit increments. The device is mechanical and requires the user to press two buttons simultaneously, which can be done through clothing.

Unlike an insulin pump, this can only give bolus doses of insulin, so you still need to take your background basal insulin using a pen or syringe. However, the advantage is that you can give your bolus doses very discretely and you don’t need to physically inject each time. People using it also said that they were less likely to miss an insulin dose and felt less stressed about taking their insulin.

The product is aimed at people with both T1D and T2D though the two unit increment means less flexibility in dosing for those who regularly adjust their insulin. The company has also announced that other OneTouch Via products are in development including a larger reservoir version, which would be helpful for those on large doses of insulin.

Glucose Monitoring

New research data on the Abbott Freestyle Libre was announced at the ADA meeting in June showing that people using the device spent 38% less time in hypoglycaemia than those using traditional finger prick testing and that use of the system reduced all measures of hypo without increasing HbA1c, compared with finger pricks. Interestingly it also showed a reduction in night time hypos by 40% and a reduction of serious hypos (below 3mmol/l) by 50%. The study, unsurprisingly, also showed that those using the Libre tested more frequently, with an average of 15 tests per day and a reduction in finger prick testing of 91%.

Abbott have also announced the availability of the LibreLink mobile phone app which enables you to use your mobile phone instead of the normal hand held Libre Reader to download your readings from the device. You simply swipe the back of your phone over the Libre to download the results. The app is free and, as well as displaying readings from the Libre, also produces several reports, such as daily trends, on your phone. The app is only currently available for Android phones (sorry iPhone users) and your phone has to be running Android 4.0 (Ice Cream Sandwich) or higher, with a screen resolution of between 480 x 800 to 1080 x 1920. Most importantly your phone has to have Near Field Communication (NFC) capability, which must be enabled.

If you’re not sure about your phone, the designers suggest that you go to Google Play on your mobile phone and search for LibreLink. If you can’t download the app, it’s probably not compatible with your phone. Also, whichever device you use to start up your sensor must then be used for the full life (14 days) of that sensor – you can’t switch between phone and reader. However, it does mean one less thing to carry with you – though you might need to be more careful about keeping your phone charged.

Meanwhile Senseonics have received CE Mark approval for their Eversense 90-day implantable CGM sensor, body-worn transmitter (worn over the sensor), and mobile app for viewing real-time glucose data. This is the first long duration CGM system and will be launched in Germany, Italy and the Netherlands this year, followed by availability in some other European countries, in a partnership with Roche.

Eversense is implanted in the upper arm in a 5-10 minute procedure by a trained doctor. A rechargeable transmitting device is worn on top of the skin, directly over the sensor, which powers the implant and sends the current glucose value and trend arrow to a smartphone. The transmitter can be taken off as required though must be replaced in order to get glucose readings. The system does require two finger prick calibrations per day and extra blood tests to confirm a reading before making any treatment decisions.

The system can alert for both high and low blood glucose levels by transmitting to the smart phone and by vibration of the transmitter.

And last but not least, Dexcom also presented data on their CGM system which showed that people using CGM use finger prick blood glucose testing less frequently but have better glucose control, fewer and shorter episodes of hypoglycemia, less fear of hypoglycemia, and improved quality of life. Dexcom will be using this data to try and persuade the FDA to allow readings from the Dexcom G5 to be seen as “non-adjunctive”, which basically means that people could use readings from their CGM to make treatment decisions (such as insulin adjustment) without having to also do a blood test to confirm the result. This ‘non-adjunctive’ label has already been awarded to the company by the EMA in Europe.

Heuristics to help in diabetes?

A new company, called Ayuda Heuristics, is starting to develop an app to help with the management of people treated on insulin, particularly those with Type 1 diabetes. But rather than just helping people track their day to day management, this company is trying to create a community that can learn from themselves and each other when dealing with the hundred and one things that can affect diabetes control.

Heuristics is “an approach to problem solving, learning, or discovery that employs a practical method not guaranteed to be optimal or perfect, but sufficient for the immediate goals”. This is something we all do in life all the time – making educated guesses when dealing with new situations – but it is also what we struggle with in diabetes management. People with T1D, when facing a new situation, try to remember what they have previously done to manage their diabetes in a similar situation and juggle a huge amount of “know how” to adjust doses of insulin based on diet, exercise, stress etc. But no matter how ‘in control’ you are, there are always days when nothing seems to work properly and, no matter what you try to do, you can’t keep that tight control, whether because it’s an unseasonably hot day, you’re more stressed than usual or you’re feeling under the weather.

Ayuda Heuristics plan to develop an app which learns with you as you live with diabetes so that it can help you make decisions, based on what is happening in your body and in the world around you. The idea is to link data from many devices (such as an insulin pump, blood glucose testing kit, fitness trackers) but also things like your diary (to help you when an important stressful meeting is coming up) or the weather report, to make suggestions as to what is happening with your control and what steps you might consider taking to try and keep things on an even keel (based on what you did last time in a similar situation). The long term aim is to then create communities of people with similar heuristics, each learning from each other’s experiences, to prompt more suggestions for how you might adjust things to manage your diabetes better.

This is an exciting new concept at a very early stage – but with the potential to use ‘big data’ to see patterns in diabetes control that can’t always be picked up at an individual level. The company are currently talking to people with T1D to develop their algorithms and are also looking for investors.

The glucagon pump

Although most people are working on a fully functional artificial pancreas, some interesting data was presented at the ADA meeting on a very different approach.

Boston University have been working on a “bionic pancreas”, a system that dispenses both insulin and glucagon and have developed the iLet as a device to administer that. However, they are still working to develop a more stable glucagon analog, as the current formulation needs to be remixed on a daily basis. As a result of this, they have been looking at the iLet as a single hormone device, and an insulin only version is likely to be the first to market but, interestingly, they have also been trying it with glucagon alone.

In this trial, with only the glucagon chamber filled, the iLet delivered very small doses of glucagon in response to sensor-detected hypoglycemia. The participants all had reduced hypo awareness and were randomized to either glucagon (mean dose 0.5 mg/day, about half the usual rescue dose) or placebo, along with using their own insulin pumps or multiple daily insulin injections, for 7 days.

The study showed a 75% reduction in time spent in hypoglycemia (below 3.3 mmol/l)) and nocturnal hypos were reduced by 91%. At the same time, there was no increase in average glucose levels recorded by the continuous-glucose monitor and the participants didn’t report the usual side effects of glucagon administration, such as nausea, vomiting or headache.

Although unlikely to be used as a stand-alone system for most people with T1D (as the concept of an artificial pancreas is meant to deal with lows as well as high blood sugars) there may be a place for a glucagon only system in people with conditions for which they would not require insulin delivery, including postbariatric surgery hypoglycemia or congenital hyperinsulinism.

Next week’s update will focus on research and other issues.

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