ATTD 2021 Distillations: Looping

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ATTD 2021 was held 2-5 June, 2021 and, thanks to dedoc, I had the privilege to attend and live tweet the presentations. However, with many sessions running in parallel, it was not possible to attend every session and many sessions covered similar topics. To address this, I watched the recordings of the sessions I missed and brought them together under common themes. Where the presentation called out that the results were confidential and/or not yet published and not for distribution I left them out of my blog but I can confirm there was nothing presented under confidence which contradicted what I am presenting in these summaries.

This is my first “distillation” covering looping. Once the domain of the online diabetes hacker community, looping (the interaction of a CGM and pump, with minimal human interaction to maintain blood glucose levels) has become mainstream with commercial looping systems available.

Specific questions covered in the presentations were:

As usual there is a TL;DR section at the end if you want to cut to the summary.

Loop vs Non-Loop: Which is Better?

Dr. Bruce Buckingham presented a study considering the Omnipod pump with Dexcom looping versus “Standard Treatment” i.e. non-looping options such as multiple daily injection or traditional pumping. For both children and adults, looping brought the HbA1c down to sub-7% levels. As we know from my previous analysis, getting the HbA1c below 7% is important to reduce the risk of long term complications.

Time in Range also improved with looping gaining more than two extra hours in range for the adults and almost four additional hours for the children.

Looping also helped with overnight highs in children and, to a lesser extent, with adults.

When looking at people with Type 2 Diabetes, there was also improvement in Time in Range and a reduction in Time Above Range.

Dr. Charlotte Boughton presented similar research showing a clear improvement of looping over multiple daily injection or a non-looping pump (HCL = Hybrid Closed Loop i.e. looping with declarations/human adjustments)

Dr. Goran Petrovski also provided details on the results of how Medtronic compared to multiple daily injection and CGM showing significant improvement in Time in Range and HbA1c.

He also showed the benefits of the closed loop system become apparent in the first few days of activation and continue to improve over the following months.

Loops Which Bolus vs Those Which Only Adjust Basal: Which is Better?

Dr. Ahmad Haidar provided a great summary of many studies comparing Automated Hybrid Closed Loop (AHCL) systems vs a “Sensor Augmented Pump with Predictive Low Glucose Management” (SAP + PLGM). To translate, comparing a system which gave “shots” of insulin against those which just managed continual rate of release (basal rate) e.g. Medtronic 780G vs 670G. As can be seen, regardless of the technology employed, the improvement was similar across the systems.

Dr. Anders L. Carlson spoke of the Medtronic study.

The results showed statistically significant improvements across all measures, including the time below range.

This was also backed up by a second and third study showing increased Time in Range and reduced time both above range and below range.

The first study showed stronger benefits for adolescents (also seen in the second study and shown on the Pivotal Study image above) and improved Time in Range (TIR) when a more aggressive endpoint was set.

The second study also confirmed the notion that a more aggressive endpoint led to an increased Time in Range and went further to suggest setting the Active Insulin Time to its lowest setting also helped improve Time in Range and lower Time Below Range.

Dr. Thekla von dem Burge showed that the benefits in the Medtronic system extended all the way down to pre-schoolers where there was a significant increase in those achieving range targets.

Dr. Boris Kovatchev presented a study using t:slim technology, instead of Medtronic, comparing Control-IQ to Basal-IQ which also confirmed a fully automated loop system improves Time in Range. It also showed the benefits begin within literally a month of employing the technology.

This study also showed the greatest benefit of the Control-IQ system was in the night time where, at its peak, it achieved 30% higher Time in Range.

As with the Medtronic studies, Time Above/Below Range was also improved with Control-IQ and also brought children’s metrics in line with the adults’.

In line with the Medtronic research, Dr. Jordan Pinsker showed the Control-IQ system provided benefit to all age groups, improving Time in Range and reducing Time Above Range.

Furthermore, the analysis showed those with poorer control (as measured by GMI, an estimation of HbA1c) achieved the greatest improvements. This is interesting because good control is often used as a selection for people to include in studies meaning much of the research could be missing a cohort who will benefit significantly from looping technology.

In line with Medtronic and t:slim, Erik Huneker also found found full looping had benefit over Predictive Low Glucose Suspend (PLGS, suspension of basal insulin when low) for people with highly unstable diabetes when using Diabeloop.

Finally, we had Dr. Roman Hovorka who, with the CamAPS looping setup, saw similar results to the other systems and great improvements in overnight management.

Is Faster Insulin Better in Closed Loop Systems?

Dr. Boris Kovatchev presented a paper comparing the performance of fast insulin to standard insulin in a fully closed loop system (no meal announcements) with moderate-vigorous exercise.

The results showed no significant difference between the standard insulin and fast insulin, as shown in the table below. Significance is indicated by the ‘P value’ in the last column. For statistical significance this value needs to be less than 0.05 which it was not across the key measures meaning the results were comparable between the two insulins and there were no significant differences.

Looking at the traces, we can see both insulins followed a similar path. The authors concluded that the algorithms were possibly better tuned to the standard insulin which gave it the comparable performance.

Dr. Roman Hovorka presented similar results when comparing Aspart and Fiasp in a CamAPS system. In terms of Time in Range and Mean Glucose, there was not a significant difference between the two insulins.

What is the Future of Looping?

Key areas of focus for looping research were highlighted across multiple talks. These include:

  • Tailored profiles for different kinds of people for better prediction (pregnancy, children, people with gastroparesis, men, women etc.)
  • Improved automation through machine learning of the individuals habits e.g. when they eat, exercise.
  • The use of additional sensors was also mentioned to aid the system predict exercise and meals
  • Simplified meal declarations to remove the need for carbohydrate counting i.e. declaring a meal and small/medium/large instead
  • The use of additional medications in the insulin mix to improve the looping system’s response to blood glucose changes e.g. SGLT-2 inhibitors, GLP-1 agonists, Amylin analogues

TL;DR

The key results of the research presented for loops were:

  • Looping vs Non-Loop
    • Benefits were seen in measures such as HbA1c and Time in Range
    • The benefits of looping systems were present in both adults and children
    • The benefits translated to literally hours per day additional Time in Range
    • The strongest improvements were seen overnight
    • People both with Type 1 and Type 2 diabetes saw improvement
    • Benefits were independent of the specific technology employed. It was looping in general which provided the gains
    • The benefits became apparent within weeks of looping being activated and were maintained for months
  • Looping with Bolus vs Looping which only adjusts Basal Rates
    • Pretty much the same results as for Looping vs Non-Loop, although there were no Type 2 studies presented
    • Setting a more aggressive target led to an improved Time in Range
    • Setting a smaller Active Insulin Time also improved Time in Range
    • The greatest improvements were seen in patients with the poorest control, as measured by HbA1c
  • Faster Insulins in Closed Loop Systems
    • Contrary to what we might predict, there is very little evidence that faster insulins provide significant benefit over slower insulins.
  • Future of Looping
    • Improved prediction through
      • Tailored, preset profiles for groups such as children and pregnant women
      • Machine learning the individual instead of the application of generic big data models
      • Additional sensors
    • Assuming they will be needed, simplified meal announcements to replace carbohydrate counting/declaration
    • Different insulin mixes to include other medications to help the looping system respond to things like exercise and meals

Displaying xDrip+ on a Wear OS Watch

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If you use xDrip+ on your phone to display your CGM, and you want to have it appear on your Wear OS (formerly Android Wear) watch, it used to be that you could pull the app onto the phone through Play Store but, alas, this is no longer supported. Here is my workaround so you can still see your glucose levels on the watch.

Finding Out the Hard Way xDrip+ is no Longer Supported

For a while I had a warning on my watch telling me to update xDrip+ and the watch face kept resetting so I thought I would bite the bullet and update it. Finding no easy way to do this, I went to Google which suggested uninstalling and reinstalling the app. Uninstalling was no problem but reinstalling proved impossible.

To get xDrip+ onto my TicWatch originally, I went to the Play Store on the watch and I installed it from there. However, this time it simply was not available. A bit more Googling revealed you can no longer install xDrip+ onto the watch via Play Store (presumably because it is sideloaded with an apk file from Github, rather than installed through the Google Store).

My Workaround

Some more Googling revealed that a workaround can be achieved with Wearable Widgets. This is an Android app which installs on your phone and broadcasts Widgets (the little graphical icon which you can put on your phone) to your watch as a Watch Face.

Once you have installed Wearable Widget, the first thing you do is add the xDrip+ widget to the screen. One widget is free but, if you want to display more, payment is needed.

Then on the watch, go to the Play Store and search for Wearable Widgets to install it. Sure enough the Wearable Widget Watch Face is now available to show the xDrip+ widget.

The last step is to go to the settings of the Watch Face and turn of “Show time above widget” so you have the time as well.
If there is a clever way to install xDrip+ now it is unsupported by Play Store I will add another post (I miss the graph) but, for now, this will do the job.

When Will We See a Cure for Diabetes?

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I received an enquiry via the Contact Me form today. It read as follows:

“Thank you for the rewarding site. Our son (5 years old) was just diagnosed type 1 out of the blue and we are already fighting to get him the best care here in the states. In your research, how far off is an effective “cure” to help with the annoyance of 4 times a day shots?”

It greatly upsets me to know children get Type 1 Diabetes. Not so much for the children themselves, as they know no different, but for the parents who will spend the rest of their child’s childhood looking out for them, monitoring their glucose levels in the night etc. and constantly worrying about their child. I replied back and thought the response may be of interest to others.

Here is my response to the query.

“Thank you for writing to me and your kind words. Obviously sorry to hear about your son but it is remarkable how quickly medical research and technology is moving.

In terms of a cure, the running joke in the Type 1 community is “a cure is 5 years away”. A joke because doctors have been saying this for decades.

In truth though, there are promising avenues from diabetes vaccines (where the immune system is trained to fight the parts of the immune system attacking the pancreas) through to “reboot” strategies for the immune system. None of these will be widespread for at least another 5-10 years though, assuming they prove successful.

Where we are seeing real improvement is in diabetes management. For example, check out Genteel for pain-free finger pricking. There are also candidates for non-invasive glucose monitoring through earrings and watches although these are still very much early prototypes.

Looping technology (having a glucose monitor talk to an insulin pump and automatically manage glucose levels) has gone from the realm of online hackers to mainstream FDA-approved devices in just a few years. A friend of mine who is at the forefront of pushing looping technology to its current limits posted this today:

“My BG (Blood Glucose) peaked at 250 this afternoon!
Mind you, I had treated myself to a whole 180g block of Dairy Milk Chocolate (so ~105g carbs). And a fruit yoghurt bowl (21g). And some other snacks but I can’t remember their carb counts.
And it did come down and flatten off in the 70s a few hours later before coming back to 90.”

Eating an entire block of chocolate and having looping technology effectively manage without intervention or injections is remarkable. He is a professional photographer who (pre-COVID) travelled the world, despite being Type 1. He is quite an inspiration and proof that Type 1 does not have to stop you achieving whatever you want in life.

Similarly, implantable beta cells are very close to reality and we will likely see this in a few years. The idea is you put an implant under the skin then size of, say, half a matchstick and it releases insulin as required, eliminating the need for injections. Eventually the immune system destroys it, after a few years, and a new implant is put in.

The new generations of insulin are also proving more and more remarkable. We now have a once-weekly basal injection, insulins like Fiasp which is faster than ever before, even faster inhalable insulin such as Afrezza, and “smart” insulins which stay in the blood and only activate when blood sugar starts increasing.

The proof the technology is improving is in the increased life expectancy for Type 1 Diabetics. It is my opinion that for a newly diagnosed Type 1 and the technology now available, there is no reason to expect them to have a shorter life expectancy than their non-diabetic contemporaries (https://practicaldiabetic.com/2020/10/22/easd-2020-life-expectancy-of-diabetics/).

Good luck and if you have any other questions, do not hesitate to email me.”

The gentleman I mention in my response, who is truly an inspiration to me and I am sure many other people with diabetes, is David Burren.

If you have questions which you would like me to answer or research, feel to also fill in the Contact Me form and I will tell you my thoughts and findings.

The Gold Standard for Treating Type 1 LADA (And Fighting To Be Recognized)

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LADA often falls through the cracks between Type 1 and Type 2 Diabetes so wouldn’t it be wonderful if the world’s greatest minds came together and determined the best approach for managing LADA? In fact they did and published the conclusions in October this year (2020).

The paper is quite long but they provided nice flow diagrams which are easy to follow. If even that is too much for you, there is the tl;dr section at the end of this post.

Diagnosing Type 1 LADA

First of all the article talks about the phenotypical characteristics (how it presents) of LADA with this table summary:

As it states, none of these categorically define LADA. Fortunately, further on, it provides a flow diagram for a definitive diagnosis:

The test starts not with a glucose tolerance test, a ketone test, or a urine test but a blood test to look for the GADA auto-antibody. As LADA is a form of Type 1 Diabetes and, as the Types are defined by their aetiology (cause), the definitive test for LADA is for an auto-antibody associated to Type 1 Diabetes (GADA).

If the blood test comes back positive, the treatment applied is dependent on the patient’s c-peptide level. C-peptide is a ‘leftover’ product from the body’s production of insulin so the c-peptide level can be seen as a measure of the body’s insulin production.

For a c-peptide level less than or equal to 0.7 nmol/L the LADA algorithm (defined in the paper) is applied. For a c-peptide level above 0.7 nmol/L, the existing Type 2 Diabetes guidelines, established by the ADA (American Diabetes Association)/EASD (European Association for the Study of Diabetes) are used, with a c-peptide re-test every six months.

If the GADA test is negative, The patient may be Type 2 (or MODY or have pancreatitis) but, if LADA is still suspected (presumably based on the broad characteristics of the disease listed above), other auto-antibodies associated with Type 1 Diabetes should be tested for.

The Type 2 Diabetes Guidelines

Here it is, modified in February 2020. The full paper can be found here. This is quite an involved flow diagram and, I will come back to it a little later on, in the context of LADA, but, if you are Type 2, it is worth a read to see if your health team are abreast of the latest recommendations. One point of note to LADAs who are being treated as Type 2s is the use of sulfonylureas for LADA patients is NOT recommended, whereas these drugs are often used with Type 2 Diabetics. The reason being sulfonylureas have been shown to accelerate the destruction of the beta cells in LADA/Type 1s and therefore will shorten the honeymoon before full insulin dependence.

The LADA Algorithm

Here it is. This is the flow diagram recommending the best possible treatment for people with Type 1 LADA, based on the latest information as of October 2020.

If your c-peptide level is less than 0.3 nmol/L then insulin should be used (basal and/or bolus, as required). For c-peptide levels between 0.3 and 0.7, metformin is seen as the gold standard and, as discussed in the Type 2 section above, NO sulfonylureas.

The rest of the treatments are based on the risk of cardio-vascular disease (ASCVD), heart failure (HF) and kidney disease (CKD). The flow is a little confusing but the treatments are GLP-1 Agonists (GLP-1RA): I talk about those here, SGLT2 inhibitors (these are a class of drugs which promote the passing of sugar out of the blood through the kidneys), and, if the patient’s HbA1c is above target, the inclusion of basal/bolus insulin.

How Do I Stack Up?

Being a typical LADA I thought I would run myself through the flow diagrams. While the hospital which treated my pre-diagnosis DKA failed to perform a test for GADA auto-antibodies (and simply assumed I was Type 2), my family doctor did and, on 3 March 2017, I was diagnosed as Type 1 LADA (my GADA levels were literally off the charts).

My fasting c-peptide level has never been below 1.3 nmol/L since diagnosis, so I fall under the Type 2 ADA/EASD guidelines (but no sulfonylureas!) Recommended treatments include:

  • Metformin
  • Weight management
  • Exercise
  • GLP-1RAs
  • SGLT2 inhibitors
  • TZDs (an insulin sensitizer similar to Metformin)

I am broadly following this recommended treatment. I use Metformin and a GLP-1RA (Ozempic/Semaglutide). I am working on reducing my weight (I fall into the ‘obese’ category for BMI) and I probably should do more exercise.

Recognizing Type 1 LADA

Based on the above recommendations, it is clear drugs such as GLP-1RAs and SGLT2 inhibitors are appropriate treatments for Type 1 LADAs with sufficiently high c-peptide levels. Yet, if we look at this Australian Pharmaceutical Benefit Scheme Press Release we see Ozempic (Semaglutide) (a GLP-1RA) is approved only for Type 2 Diabetes. The other GLP-1RA available in Australia, Trulicity (Dulaglutide), is also only approved for Type 2 Diabetes. The consequence is, instead of paying $41 a month for this recommended medicine, LADAs such as myself pay $140 per month. The $1,700 per year cost talked about in the PBS press releases is the reality for Type 1 LADAs in Australia. Moreover, while there are “Safety Nets” for PBS approved medicines, for a LADA like myself who is obtaining the recommended treatment under a “private prescription”, no safety net applies.

While having to constantly explain that insulin independent Type 1 Diabetes is a reality to medical professionals or on social media is frustrating, the significant financial impact of ignoring LADA means there are Type 1 LADAs here in Australia (and in other countries which naively consider medications as strictly “Type 1” or “Type 2”) who are not getting the appropriate treatment for their disease and this is having a direct impact on their quality of life and their ability to contribute fully to society.

tl;dr

The definitive test for Type 1 LADA is a blood test for auto-antibodies. The most common auto-antibody is GADA but, if this is negative and LADA is still suspected, other auto-antibodies associated with Diabetes should be tested for.

Once LADA is established, the treatment depends on the c-peptide level of the patient. If the c-peptide level is below 0.3 nmol/L, the patient should use basal/bolus insulin, as needed. For c-peptide levels above this, recommended treatments include:

  • Metformin
  • Weight management
  • Exercise
  • GLP-1RAs
  • SGLT2 inhibitors
  • TZDs (an insulin sensitizer similar to Metformin)

Sulfonylureas are NEVER recommended for Type 1 LADAs.

Sadly, in many countries, some of these treatments, such as GLP-1RAs are not recognized as appropriate for Type 1 Diabetics, including LADAs, and, therefore, are often not covered through government subsidy schemes or health insurance. If this is the situation where you live, and you are a LADA who cannot access the medications for your disease, I strongly encourage you to petition the appropriate bodies to get the guidelines changed.

A Cooling Pouch For Less Than US$5 To Help Keep Your Insulin From Overheating

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If you have seen the Glucology or Frio insulin pouches you will already understand the concept of an evaporative cooling insulin pouch. They work really well but the downside is the price. For a two-pen pouch you are looking at around US$30. In this blog I will show you how to make your own for less than US$5 (if you have a sewing machine) or, if that is too much hassle, you can buy a ready-made one from my Etsy shop for around US$20 including shipping anywhere in the world or AU$25 including shipping within Australia. For every one purchased, I will be supplying an identical one to charities around the world who are supplying insulin in developing countries where refrigeration is unreliable.

How Do They Work?

Evaporative cooling pouches work off of the idea that if water is evaporating from something, that something gets cooler. This is how humans cool themselves i.e. sweating. The key technology in the cooling pouches that allow them to remain cool for well over 24 hours are the little beads inside the pouch. These hydrophilic beads (a big word meaning they hold onto water) are the same ones you might know as Orbeez or those squishy spheres you see flowers in sometimes.

Magic Moisturizing Crystal Mud Soil Water Beads For Flower Planting Super absorbent polymer Crystal Soil Jelly Balls Home Decor|soil water beads|water beadscrystal mud - AliExpress

Same technology, different application. While the beads love holding onto water, it still evaporates and, while it does, they and anything they are surrounding feels cool to the touch. Embed them in material and that material, and anything it is surrounding also becomes cool.

DIY Step One: The Materials

Firstly, you will need two cooling scarves. They look like this:

You can buy these from Amazon but this will set you back about US$4 each before postage. Go to Ebay and select the international option and, while it might take a little longer to arrive, you can pick them up for around US$1 each.

You will also need a sewing machine or someone with the time to hand stitch them.

DIY Step Two: Stitching

Lay one on top of the other. For symmetry, I have put the seam of one (the white stitching on the edge) to the non-seam side of the other.

Then you will want to do a straight stitch along the edges so the two pieces form a long tube.

The dark line at the bottom on the scarf in the above picture is the straight stitch you need to do on the top and bottom. There is one at the top in the image as well but, because I was using a light brown thread in my bobbin, it is a little tricky to see. While I went a little over in the above picture, you want to go up to the white stitching which runs up and down on the left hand side in the above picture. This gives you the ties on the end of the scarf to secure the pouch, once finished.

DIY Step Three: Inverting

Arguably the fiddly bit, you now push the tube inside of itself to invert it and hide the stitching. I found the best way was to pull it out, rather than trying to push it through with a stick. In the end you will have an inverted tube which looks something like this.

You are now the proud owner of a cooling insulin pouch. Well done!

How To Use Your Pouch

Before use you will need to soak your pouch. I recommend no more than five minutes. Any more than this and the beads will absorb too much water and make it too hard to insert the pens/cartridges/vials. There is probably a risk of splitting the stitches as well.

Once soaked, dry it off with a dishcloth or towel. The material does not have to be wet for it to be effective. It is the beads inside which do the work.

Then, you can insert your hardware.

In the above example, I have my basal and bolus insulin pens and a MedAngel (a Bluetooth thermometer which connects to your phone).

Once inside, you can use the those end ties to keep it all together.

Does It Really Work?

While I am still insulin independent, I always carry insulin whenever I travel overseas for work. Just before the world locked down, I took my pouch to Singapore. Even with Singapore’s humidity, the pouch, within my backpack, was effective at keeping my insulin cool as I walked, in the direct sun, to the office each morning. Tests I have conducted in more controlled conditions show the pouch is as effective as its commercial counterparts.

Here you see three temperature gauges measuring (in Celsius) the temperature in my house (the middle one), the temperature of a commercial pouch (on the left) and my one (on the right). Even inside, both pouches shaved off 2-3 degrees Celsius (4-6 degrees Fahrenheit). The effect becomes even stronger in direct sunlight where I have seen temperature differences of 10 degrees Celsius (20 degrees Fahrenheit) between the ambient temperature and the pouch.

“Recharging”, Storage and Care

The pouch will continue to keep the contents cool for over 24 hours. When you want to “recharge” it, immerse it in water for no more than two minutes. Again, if you over-immerse, you risk expanding the beads too much and making it impossible to insert your pens etc. or breaking the stitching.

If you are not planning on using your pouch for a while, let it completely dry out in the sun or on an air vent and, when completely dry, store it in a cool, dry place.

EASD 2020: Life Expectancy of People with Type 1 Diabetes (A Review of Hope)

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Let me cut to the chase on this: if you have been recently diagnosed with diabetes and you maintain good glucose control, based on this evidence, there is NO reason to expect you will not live a long and healthy life

This may sound wrong because it is easy, from a statistical point of view, to work out the difference in life expectancy between people with diabetics and non-diabetics and show people with diabetes live for a few years less than non-diabetics. Sure enough, Mike Stedman and his colleagues did precisely this for EASD 2020.

What this tells us is that Type 1 males live 7 years less than their non-diabetic counterparts and, for women, it is 8.5 years. For Type 2, the difference is less pronounced being 1.4 years lost for men and 2 years lost for women.

The problem is the data, while accurate, is very misleading. Moreover, it hits social media and diabetes groups, and Type 1s think it is inevitable that they will live shorter lives than their friends and families. The stresses of diabetes are plentiful without this kind of burden being added on top.

The fact of the matter is this graph says absolutely nothing about the life expectancy of an individual. Rolled into that average life expectancy are hypo deaths, DKA deaths, and things like heart complications. We know higher HbA1c levels increase the risk of cardiovascular (heart) disease so, for someone with good glucose control, in my opinion, the above graph is meaningless. It also says nothing about age of onset. Someone who was diagnosed 50 years ago (included in the above numbers) had to manage their diabetes with urine, thick needles, and a lot of luck. Someone diagnosed today has much more effective tools at their disposal.

In my opinion, it would be much smarter to look how life expectancy has improved over the years and, where possible, see if it is catching up with the non-diabetic population. This is what I want to write about today. As usual, you can skip to the tl;dr for the summary, otherwise let us go on a journey of optimism, rather than of pessimism. Firstly though, what is up with that gender imbalance in life expectancy?

Why Do Females with Diabetes Have a Shorter Average Life Expectancy?

Again, let me repeat the disclaimer: Average life expectancy says nothing about the life of an individual. A woman with good glucose control has, in my opinion, no reason to expect any shorter life than her non-diabetic peers.

To the question at hand though, another presentation at EASD 2020 looked at this in some detail. Juergen Harreiter presented “What you need to consider for individualised gender-sensitive care”. This looked at the gender differences in diabetes risk and treatments.

Sure enough females with diabetes are at a higher risk of coronary heart disease and stroke than their male counterparts.

and a 40% greater risk of all-cause mortality.

Specific reasons, backed up by data, were light on the ground except for this cited study.

In the above graphs, we have four drugs commonly used to reduce the risk of heart disease. For three of them (statins, RAAS blockades, and beta-blockers) women were routinely under-treated. With males receiving more aggressive treatment, it is not surprising they live longer.

So What About Life Expectancy Improvements over Time?

There is overwhelming evidence that life expectancy is improving every year for people with diabetes. While the cause of the improvement is not always clear, I suspect it has to do with improvements in management technology (insulin improvements, pumping, glucometers, looping etc.) and possibly improved knowledge and education about the disease. Let us go through the papers I have found.

Life expectancy and survival analysis of patients with diabetes compared to the non diabetic population in Bulgaria (2020)

This study looked at data from 2012-2015 using national databases. Even in this short period of time we see improvements across both Type 1 and 2 and across genders.

While the non-diabetic population did not move at all in their life expectancy, Type 1s, Type 2s, Type 1 females, and Type 2 females all gained around an additional year, on average. Moreover, by 2015, the overall life expectancy of people with diabetes was about the same as the non-diabetic population (almost 75 years).

Improvements in the Life Expectancy of Type 1 Diabetes (2012)

In this study the life expectancy of two cohorts was examined: people with diabetes diagnosed between 1950-1964 and between 1965-1980.

Here we see the percentage of survivors after a certain age. The EDC (Pittsburgh Epidemiology of Diabetes Complications) cohort for 1950-1964 are lower on the graph as fewer survived over the years. In comparison, the 1965-1980 cohorts for EDC and ACR (Allegheny County Type 1 Diabetes Registry) had a much higher survival rate again showing the difference just 15 years made in the life expectancy of people with diabetes.

Long-Term Mortality in Nationwide Cohorts of Childhood-Onset Type 1 Diabetes in Japan and Finland (2003)

This study was designed to compare Type 1 diabetics in Japan and Finland but also had information of improved survival rates over the years.

While in Finland, the survival prospects of a Type 1 child remained excellent for the periods 1965-1969 and 1975-1979 with only minor improvements, we see there was a dramatic improvement in survival probability for children diagnosed in the latter period for Japan.

The 30-Year Natural History of Type 1 Diabetes Complications (2006)

This study looked at five 5-year cohorts (1950-1959, 1960-1964, 1965-1969, 1970-1974, and 1975-1980) also from the Pittsburgh Epidemiology of Childhood-Onset Diabetes Complications Study. Not surprisingly, it came to similar conclusions.

We see a clear improvement in survival rates with around 60% of those diagnosed in the 50s and living with the disease for 30 years surviving, compared to around 95% for those diagnosed in the 70s.

All-Cause Mortality Trends in a Large Population-Based Cohort With Long-Standing Childhood-Onset Type 1 Diabetes (2010)

This study split the previously mentioned ACR study into three diagnosis cohorts (1965-1969, 1970-1974, and 1975-1979) to compare survival rates.

As we have seen in the other studies, there was a dramatic improvement in survival rates between someone diagnosed in the late 60s compared to the 70s.

A Word of Warning

In the above studies we have looked at people with diabetes in Bulgaria, USA, Japan, and Finland and, as mentioned, it is likely the improvements are due to improvements in medical technology and education. For countries where these improvements are not available, there is no reason to expect the same gains. For places in the world where insulin is not readily available, there is no reason why life expectancy should be much better for a person with diabetes than it was before the discovery of insulin 100 years ago. These studies show there are compelling reasons for insulin to be available to all who need it, across the world. We are literally robbing people of decades of life if we choose to do nothing.

tl;dr

There is clear evidence that the survival rates for people with diabetes has improved for those diagnosed between 1950 and 2015. Furthermore, in a study from Bulgaria by 2015, the life expectancy of people with diabetes was the same as non-diabetics.

While the specific cause of the improvements was not examined, it is assumed to be a function of improved technology (insulin, pumps, glucometers, looping etc.) and improved understanding and education of the disease.

Therefore, if you have been recently diagnosed with diabetes and you maintain good glucose control, based on this evidence, there is NO reason to expect you will not live a long and healthy life.

Bringing Consulting Skills To The Medical Industry

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Outside of writing these blogs, I have a day job which involves the implementation of software to help organizations manage their customers and processes more effectively. I have been doing this job for around 20 years and worked at a couple of the “Big 4” Consulting companies along the way. It is fair to say I understand a thing or two about professional consulting.

Yet, when I go to conferences and hear medical professionals speak, or when I visit diabetes forums and hear of diabetics’ experiences with medical professionals, it is clear there is a problem. For my own medical team I could not be happier. Our conversations do not focus on ‘adherence’ and ‘non-compliance’ but on working together to find the right solution. For other diabetics this is not the case causing mental stress for individuals who, for the most part, are doing everything within their power to stay healthy.

A great example highlighting the problem was this image recently posted by Renza Scibilia.

Image

While not every software implementation project is a success, I would never dream of giving a ‘report card’ to my clients. They are paying me and the company I work for to give them the best possible advice and give them the best possible chance of success. To give my client a rating would be the height of arrogance and conceit and shows a profound misunderstanding of the relationship between us. If my client fails, I have failed and a rating is as much an indictment, if not more so, of my consulting than it is of the client who paid me to deliver success.

The fact is, the relationship between a patient and a doctor, especially a medical specialist, is no different to the relationship between a client and a professional services consultant. The stakes may be higher in the medical field but the dynamic between the consultant and the client should be the same. So what can we apply from professional consulting to modern medicine? As usual, if you want to get to the destination without going on the journey, you can always skip to tl;dr.

People, Process, and Technology

It is well known in IT consulting that the success of a project goes beyond the technology. A common framework for considering the various factors of a project is to consider the People, Process, and Technology.

Leon's CRM Musings: The Interplay of People, Process and Technology

In this model we have:

  • Process: Something we are trying to manage, essential to the ‘health’ of the business
  • People: Those affected by the process
  • Technology: The tools used to manage the process

Only when these are considered together is the project likely to be a success.

The parallel model for a patient is not a huge stretch:

  • Process: The disease i.e. diabetes
  • People: The patient
  • Technology: The medications and technology used to manage it

Implementing technology with no consideration of the other two factors is almost always a disaster. In the same way, throwing drugs at a patient with no consideration of who they are or how the disease affects them in their day-to-day life is an incomplete solution.

Just as every workplace has similar processes but each has their unique aspects so too with patients and their diabetes. Is it practical for the patient to inject multiple times per day given their job/circumstances? Can they afford the drug/pump/CGM/test strips you are recommending/prescribing? Does the patient have the necessary training/knowledge to manage their medication/technologies effectively? If the answer to one of these is “no”, is it really the patient’s fault when they fail to meet the doctor’s expectations? Is it a case of adherence/non-compliance or a consultant failing to do their job?

As Sir William Osler famously said:

The Trusted Advisor

The ideal situation for a consultant is to be considered a trusted advisor. If the client sees you this way it means they trust you to do the right thing by them and they are more likely to follow your suggestions and, as importantly, confide in you when they feel your ideas may not work.

In my opinion, there is little room for ego when it comes to being a trusted advisor. While you are the expert, humility goes a very long way. It should be very clearly understood who is paying for a service and who is providing that service. The consultant is there at the pleasure and to serve the client, not the other way around.

Being a trusted advisor maximizes the chance of a long term relationship. I have clients who I have been working with for over 15 years, despite working for multiple companies in that time. My clients come to me because they know I will give them the best possible advice I can to help them and not make them feel stupid in asking.

The Client Knows More Than The Consultant

This sounds counter-intuitive given the consultant is being paid for their expertise. However, from a disease perspective, someone who has had diabetes for 20 years will likely know more than a general practice/primary case doctor and are probably more up to date on the latest literature. Why is this the case? Because a doctor gets, at most, an hour or two on diabetes in their entire multi-year training to become a doctor. Whereas someone with diabetes has a strong motivation to understand the latest information on their disease. This will not be as applicable to diabetologists/endocrinologists but it is still completely true for the other aspects of the patients’ life.

In fact, this is probably the hardest lesson for a professional consultant to learn: sometimes the client will ignore your advice and they are completely right in doing so, no matter how insistent you are that it is a mistake.

In professional services, the client knows their business better than the consultant ever will. Therefore, if a consultant provides two options: a good one and an ok one, sometimes the client will still go with the ok solution because they know it has more chance of success despite the consultant’s insistence that the other solution is better. Even if the consultant is not considering the People and Process, the client will be.

What Can Patients Do?

The most productive relationships and best outcomes I have had with my clients is when they invest the time to learn all they can about the technology being implemented. Getting educated gives them the power to ask the right questions and get better solutions; they understand the strengths and weaknesses of different approaches and can challenge the consultant’s assumptions.

If, as a diabetic, you are keen to learn more about your disease and how it is treated, here is a blog article where I provide references to a raft of educational resources. It was using resources like this that allowed me to propose medications to my endocrinologist, based on the latest research, which seemed to lead to a better outcome. She considered my proposal, did her own research and, together we found a solution. This is how we continue to work today.

tl;dr

As a professional consultant with over 20 years experience, I understand the intricacies of working with clients to give them advice and steer them towards success. There are many great medical professionals out there but, based on what I see in diabetic forums and the language used in conferences, it is clear that some professionals could employ a consulting approach towards their patients.

While I could probably write enough to fill a book on professional consulting techniques and their application to medical professionals, I have limited this article to three key concepts:

  • Treating a disease goes beyond medication. The phenotype of the disease for that individual, as well as their personal circumstances are crucial elements to consider
  • Humility goes a long way in building a trust and rapport. Understanding that the doctor is simply someone being hired for their knowledge and skills is a good start to fostering such a relationship
  • Despite the consultant believing they know all the answers, sometimes the patient will ignore the consultant’s advice and it is completely the right thing to do. The patient will always know more about their disease and their personal circumstances than the doctor will

Finally, as a patient, it is in your best interest to understand, as well as possible, your disease and the medication options. This will not only mean you can ask the right questions but also improves the prospect of working with your health case team for the best possible solutions.

EASD 2020: A Weekly Basal Insulin Being Developed

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I am coming to the end of my EASD 2020 series but what a conference it was for announcements and discoveries. It just goes to show that research into diabetes is thriving and it suggests we have a lot to look forward to in the future with continual advancements in medical treatments and technology,

The presentations on Insulin Icodec, a once-weekly basal insulin, was particularly exciting for me.

What is Insulin Icodec?

Insulin has come a long way in the last 100 years. Early forms of insulin were derived from farm animals but, with the advance of recombinant DNA (the ability to combine DNA from multiple sources), it became possible to manufacture insulin with bacteria or yeast. Mass production of ‘regular’ insulin (human-equivalent) followed until the mid-nineties. In 1996 a new form of insulin was introduced to the market by Eli Lilly in the form of ‘Lispro rDNA’. This was a genetically modified form of insulin which acted in the body like regular insulin but with modified properties.

Since then, insulin analog advances have been made to improve how quickly a rapid-acting insulin takes to reach peak activity or, in the case of basal insulins, to make them last for longer and more consistently in the body.

Insulin Icodec is very much in this second camp. While some basal insulins, up until now, could work for around 24 hours, this is not the case for Icodec which makes basal insulin available to the body over a period of one week.

Presentations

Ulrike Hoevelmann presented on the effectiveness of the insulin. As we can see here, it maintains a relatively constant supply of insulin to the body over the seven days.

This particular research involved 50 participants and explored the properties of Icodec compared to Degludec (Tresiba).

Julio Rosenstock presented on a study with 247 participants comparing daily basal injections with weekly injections in a double-blind, double-dummy test. Once-weekly insulin Icodec showed a higher rate of hypoglycaemic events, compared to daily basal insulin glargine U100.

However, Doctor Rosenstock was quick to point out the only difference which was statistically significant was the Level 1 hypos. In all other aspects compared, there was no statistically significant difference in outcomes or adverse events between the two insulins.

Only For Type 2s?

Both studies focussed exclusively on Type 2s. So, will Icodec also work for other Types, such as Type 1? I asked this in one of the presentations and was told it certainly will but this is not where they are researching right now. My guess is the research trials are focussing on the majority of diabetics i.e. Type 2s. It is still early days so I am sure, before Icodec reaches the market, it will also be tested in Type 1s. While some Type 1s I know have expressed concerns around the risks of being subject to a bad dosing decision for an entire week, I think this would affect all patients about the same, regardless of Type. Personally, I think the more technology can remove the burden of management from diabetics and carers, the better and going from 365 injections a year down to 52, for me, is compelling.

Time In Range – The New HbA1c

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Most diabetics, certainly most Type 1s, know their HbA1c. As described previously, the HbA1c is a measure of the ‘average sugariness’ of the blood over the last three months. As a diagnostic test, the HbA1c has been with us for a little over 40 years and has served us well. However, as technology has improved for the management of diabetes, the ways we keep tabs on our blood has also evolved and a new measure: Time in Range is growing in popularity among both diabetics and researchers alike. In fact, quite a few talks at EASD 2020 spoke directly at Time in Range and linked it to the long term health of diabetics.

In this blog I will talk about what the HbA1c tells us, its limitations, and the additional insights we can gain through the Time in Range. As usual, at the end, we have the ‘Cliff Notes’ tl;dr.

Benefits of Measuring the HbA1c

As I have shown previously, many papers examine the relationship between long term HbA1c and complications and this was reiterated by Professor Pratik Choudhary at EASD 2020 with this excellent graph.

The Limitations of the HbA1c

While of diagnostic value, there are limitations with the HbA1c measure.

Firstly, the measure assumes the lifespan of the red blood cells as part of the calculation so, if this assumption is invalid, it can affect the HbA1c. Common causes of false HbA1c readings include:

  • Anaemia
  • Excessive alcohol consumption
  • Excessive use of opiates
  • Pregnancy
  • Blood transfusions

The second and arguably biggest limitation of the HbA1c measure is while it speaks to the ‘average sugariness’ it says nothing of the variation. This is why, historically, doctors have erred on the side of a higher HbA1c with Type 1s, often to the diabetic’s frustration. The reason is simple: if the diabetic’s glucose levels fluctuate significantly, and they keep a lower glucose level, they are at an increased risk of hypo whose effects are immediate (groggy, fall over, go unconscious etc.) whereas running a little ‘high’ and fluctuating mitigates the risk of hypos at the expense of increasing the risk of long term nerve damage. To put it simply, with limited visibility of the fluctuations using strip glucose monitors, it makes sense that doctors err to minimize risk today and encourage their patients to run a little higher with a view that the longer term risks can be managed later.

Interestingly, in his talk, Professor Choudhary blamed his patients for running high and having high fluctuations, suggesting they are driven by fear of a hypo which then leads to over-correcting and large fluctuations.

Fortunately, Continuous Glucose Monitoring (CGM) technology gives a much clearer picture of the fluctuations, informing both the doctor and patient, and allowing them to proceed informed, rather than out of fear.

Time in Range

It has taken a while for a standardization of Time in Range guidelines but in August 2019 we got one from the ADA.

The standard is adjusted for various sub-groups of diabetics.

What is more, these ranges are not random, or at the whim of some group of doctors, but backed up by statistically significant links to both long term complications and the equivalent HbA1c.

Some of these were highlighted by Professor Richard M. Bergenstal.

and Anass El Malahi at EASD 2020.

As we can see, we can link changes in Time in Range to changes in the risk of retinopathy, microalbuminuria, microvascular complication, and nephropathy.

Professor Bergental also showed, using the CGM data of three of his patients, how much more insightful Time in Range can be, compared to HbA1c.

Here the three patients have exactly the same HbA1c but very different experiences with their diabetes. with the third patient spending a lot more time in hypo and much less time in range.

Bringing together the Time in Range with the latest data on what it means for long term complications, the Ambulatory Glucose Profile (AGP) Report captures the key metrics along with statistically significant guidelines in one page.

As we can see the report captures:

  • Percentage time in the different BGL ranges
  • Average Glucose
  • Glucose Management Indicator (GMI): an estimation of the HbA1c
  • Glucose variability: a measure of fluctuation

which, given the GMI on its own is a proxy for the HbA1c, shows we are considering a lot more information in the AGP report than simply ‘average sugariness’.

The Big Problem with Time in Range

The big problem with Time in Range analysis is it requires a Continuous Glucose Monitor (CGM) to capture the data: it is a metric of privilege. While many of us have no exposure to it in the West, in places like Mexico, some Type 1 diabetics are given literally one strip per day to manage their blood glucose levels. Fortunately, research shows the proportion of finger pricks in, below or above range can still be correlated to HbA1c estimations and, therefore, give an indication of long term risk.

Also, with an increase in Time in Range of 10% leading to a lowering of HbA1c of 0.5%, using the above, we see that for someone whose finger pricks are in range 70% of the time, this correlates to an HbA1c of roughly 7%, as with the CGM data. This means the AGP Report and the guidelines it contains can be applied to CGM or finger pricking equally. So, while a diabetic’s management technology may change over time, their reporting for their health care team does not have to.

tl;dr

With the advent of Continuous Glucose Monitoring (CGM) we have new and insightful ways of examining our data beyond what is available with finger pricking and the HbA1c. One such way is analysing the Time in Range of our data. Time in Range provides a wealth of knowledge about both average sugariness and the glucose level fluctuations. One way to present this information is with an Ambulatory Glucose Profile (AGP) Report.

While driven by CGM technology, it is possible to use the AGP Report with finger pricking by considering the proportion of results that fit in the low medium or high categories. This now means we have a common report whether we are finger pricking or using CGMs.

Clinical research using Time in Range analysis has also established that it is predictive for a range of long term diabetes complications. This means, Time in Range analysis and the AGP Report are now a viable alternative to the HbA1c and provide much richer insights.

The Benefits of Incretin Mimetics For All Diabetics

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I first read about incretin mimetics in Dr. Bernstein’s fourth edition of “Dr. Bernstein’s Diabetes Solution” published in 2011. He devotes nine pages to this class of drugs and it is a good place as any to describe what they do. It should be noted for those unfamiliar with Dr. Bernstein, his focus is on the treatment of Type 1 diabetes. While incretin mimetics are sometimes hailed as a ‘Type 2 drug’, they can be of benefit to diabetics of all Types as I will show in this blog.

From there I will update the information based on some peer reviewed papers from recent years (specifically relating to LADA) and the presentations at the recent EASD 2020 conference and then onto my own experience using them. As usual, there is the tl;dr at the end if you want the short version.

What Are Incretin Mimetics?

To understand the role of incretin mimetics, it is important to understand that beta cells produce, not just insulin, but also another hormone called amylin. Amylin is a ‘satiety’ hormone i.e. it makes you feel full. So, as the beta cells become damaged they are less able to produce this hormone. Amylin is released in response to the presence of ‘gut hormones’ in the blood, released when the gut is stretched. These ‘gut hormones’ are called ‘incretins’.

Based on all this, Dr. Bernstein suggests that diabetics of all persuasions are likely to not feel as ‘full’ as their non-diabetic counterparts. For me, this poses the question: “If someone who has impaired beta cell function cannot effectively regulate their eating, is it possible Type 2 diabetes and pre-diabetes causes obesity and not the other way around?” but that is a blog for another day.

At the time of writing his book, Dr. Bernstein describes incretin mimetics as being used to lower blood sugar levels after meals and for weight loss. We now know they have many more effects on the human body.

GLP-1 Receptor Agonists (GLP-1RAs) are one such incretin mimetic. As per the above we see, among other things, they can:

  • Lead to weight loss (likely due to the increased sensitivity to feeling full)
  • Lower glucagon secretion (meaning the liver releases less glucose into the blood)
  • Stimulate insulin secretion and production (to process the food that is causing the stomach to feel full)
  • Decrease beta cell apoptosis (this is the fancy name for programmed cell death. Cells in the body are given a countdown clock. When that clock reaches zero the cell destroys itself. Incretin mimetics tinker with that clock to extend the life of beta cells)
  • Offer protection from heart disease
  • Lower blood pressure

I should note that while these drugs do stimulate insulin production like, say, sulfonylureas unlike ‘sulfs’ the evidence shows this does not accelerate the demise of the diabetic’s honeymoon. My guess is the suppression of apoptosis counters the effect. Another possible explanation is, because the insulin is getting triggered earlier and harder, the blood sugars are not getting the opportunity to rise as high. Dr. Bernstein talks about how it takes more insulin to bring blood sugar down by a fixed amount when it is at a high level than when it is lower. So, the mimetics get the insulin out early when it is more effective and therefore the net production for a given meal is less.

Types of Incretin Mimetics

There are three types of incretin mimetics. These are:

  • Amylin analogs: To my knowledge the only one on the market is Symlin (pramlintide). This is available by injection. I have not tried this one. EASD 2020 had a presentation on using it in a dual-hormone therapy (pumps with insulin and pramlintide) but the benefit of the additional pramlintide, in this context, was minimal.
  • GLP-1 agonists (mentioned above): This is mentioned above with the associated effects. Until recently this was also only available via injection. Recently an oral version has been released (more of that later). I am currently on a once-weekly injection of this drug. Here are the six GLP-1s on the market at the time of writing.
  • DPP-4 inhibitors: DPP-4s destroy GLP-1s in the body so this drug opposes that destruction and therefore, in principle, eliminates the need to inject GLP-1s. DPP-4s are available in an oral form and I took these for at least six months before moving to the GLP-1 agonists.

Contraindications and Side Effects

I will list some of the more common side effects but this list, like for most drugs, is far from exhaustive so discuss your specific history with your health care team to get a full picture of how well these drugs might suit your circumstances and complication risk profile.

Firstly, incretin mimetics slow stomach emptying so this can make gastroparesis (a condition not uncommon in Type 1s) worse. This slowing can also induce nausea. People on social media will be more than willing to tell you how incretin mimetics made them violently ill. For me, I feel mild nausea a day after injecting the GLP-1 agonist (akin to very mild car sickness) but felt no such effect when taking the DPP-4 inhibitors.

One side effect that was actually beneficial for me was constipation. As I also take Metformin, I have found the GLP-1 agonist and Metformin balance themselves out nicely giving me a lot of freedom I did not have when taking Metformin with the DPP-4 inhibitor. It is different for everyone though as GLP-1 agonists are also reported to have diarrhoea as a side effect.

One of the more serious side effects is the risk of reversible pancreatitis. I am informed pancreatitis is one of the most painful things you can experience and is usually characterized as a sudden, severe abdominal pain extending through the body from the back to the front. As the name suggests, stopping the medication reverses the condition.

LADA-Related Studies on DPP-4 Inhibitors

Given I am a Type 1 LADA trying to preserve my beta cells as long as possible and avoid the financial and mental stresses of insulin management, many of the studies I have earmarked, up to EASD 2020, are focussed on blood glucose management and beta cells preservation. Here are a few:

Presentations From EASD 2020

Tina Vilsbøll presented on Semaglutide, a new GLP-1 which can be taken as a once-weekly injection or as a once-daily oral pill, both being equally effective.

Juris Meier went into more detail as to the efficacy of the oral version, compared to other GLP-1 agonists, in Type 2s, showing it was more effective at reducing HbA1c.

The oral version of Semaglutide also compared favourably to the DPP-4 inhibitor Sitagliptin at doses above 3mg for Hba1c reduction and weight loss.

The downside was an increase in adverse reactions at the higher doses, compared to Sitagliptin.

So, if you are considering swapping out Sitagliptin for Semaglutide, understand that for a superior effect on HbA1c and weight loss you are also at a greater risk of those adverse effects.

Alice Cheng showed how the injectable version compared favorably to both DPP-4 inhibitors and other GLP-1 agonists for reducing HbA1c and weight loss.

For adverse effects, Semaglutide was comparable to other GLP-1 agonists.

My Experiences With DPP-4 Inhibitors and GLP-1 Agonists

As mentioned, I have used both in an attempt to preserve my beta cell mass. For me, the DPP-4 Inhibitor had no side effects or, at least, any side effects were washed out by the ones from Metformin. The DPP-4 Inhibitor did nothing for me in terms of HbA1c reduction (although it is already in the mid-5% for this is not surprising), satiety, or weight reduction.

My experience with the injected GLP-1 agonists has been very different. Given the trouble I was having with Metformin, I halved that dosage but found the two drugs balanced each other nicely, as touched on before. I have lost five kilograms over a couple of months (I have it to lose) which I attribute to my significantly reduced appetite and improved sense of satiety. It is only now I realise it has been years since I actually felt full eating food and the GLP-1 agonist has given this back to me.

tl;dr

While traditionally considered a ‘Type 2 drug’, there can be benefits in incretin mimetics for all Types of diabetics. For all Types we have the general benefits of:

  • Lowering blood pressure
  • Lowering the risk of cardiovascular disease
  • A sense of feeling ‘full’ which may be lacking in diabetics
  • A lowering of HbA1c
  • Weight loss (especially for the GLP-1 agonists)

For Type 2s, the benefits also include the lowering of blood sugar levels through the increased release of insulin after meals and supressed release of glucose from the liver.

For Type 1 LADAs there is growing evidence that incretin mimetics can help preserve beta cell function and prolong the honeymoon. Certainly the latest guidelines for managing LADA fully embrace incretin mimetics even if, formally, they are not approved for use in Type 1s.

In terms of side effects, incretin mimetics can cause stomach issues and nausea but, generally, these are mild and much less pronounced in DPP-4 inhibitors.

New innovations in incretin mimetics include:

  • An improved once-weekly GLP-1 injection and
  • An oral GLP-1 taken once-daily

While superior to similar products on the market in terms of their effects on HbA1c and weight loss, it comes at the cost of increased risk of side effects such as nausea, diarrhoea, and vomiting.