EASD Highlights: Hypoglycaemia & Guidelines Consensus

Prof Kamlesh Khunti 


October 02, 2020

Prof Kamlesh Khunti presents his personal highlights from the virtual European Association for the Study of Diabetes (EASD) 2020 Annual Meeting.

This transcript has been edited for clarity.

Hello, my name is Kamlesh Khunti. I'm professor of primary care diabetes and vascular medicine at the University of Leicester.

Thank you for joining me today for a couple of highlights from the EASD we have just attended recently, virtually unfortunately.


First of all, I attended a really interesting session that I was speaking at as part of the International Hypoglycaemia Study Group (IHSG). This was by Professor Stephanie Amiel, King's College London, who gave a very eloquent presentation on what's clinically meaningful in terms of the reduction for hypoglycaemic episodes. This has never been attempted before, and she took us through why, what, who, and how much?

Why - we know in terms of hypoglycaemia has a major impact not only on microvascular complications and microvascular complications and mortality, but also the massive and the significant impact on the person with diabetes in terms of psychological impacts, such as fear of hypoglycaemia, and the changes they make following hypoglycaemia.

The what, in terms of the definitions she gave of hypoglycaemia.

The International Hyperglycaemia Study Group has recommended three levels of hyperglycaemia:

  • Level one - the hypoglycaemia alert at 3.9 mmol/l - we should be doing something about it if we see that

  • Level two - of less than 3 mmol/l - this is clinically important so that we don't get people going to severe hypoglycaemia

  • And finally, level three – the severe hypoglycaemic episode - that is exactly what we want to avoid

The 'who' is in terms of the people with both type 1 and type 2 diabetes.  And then the rest of the discussion was on how much reduction is clinically meaningful.

So if we can define this, we can then make recommendations to bodies that are licensing therapies, or making guideline recommendations. What is the clinically meaningful difference in hypoglycaemia that one could get comparing one treatment to another treatment?

So there's a number of ways that we can look at this and she went through each of the potential mechanisms.

We know we have this for other conditions, such as blood pressure reduction, LDL cholesterol reduction, body weight reduction, and HbA1c reduction, we have good criteria on what is clinically meaningful, and these are how we make decisions on which therapy to use compared to other therapies.

But this hasn't been attempted for the reduction in hypoglycaemia risk.

And the kind of things that we should be thinking about she went through was first of all looking at severe hypoglycaemia reductions with various therapies. And she gave data on some reductions that have been seen in a number of studies with severe hypoglycaemia reductions that range in type 1 and type 2 diabetes from anything from 29% to 58%.

One could look at non-severe hypoglycaemic risk, which showed evidence between 30% to 39% reduction. One could use certain scores, such as the Gold Score, which gave us really nice data on CGM reductions, timing range, for example.

And then finally, cost effectiveness that could be looked at. But there's very little data on cost effectiveness. She gave something on HypoAna, which was well within the National Institute for Health and Care Excellence (NICE) recommendations of £20,000 cost per QALY.

So this is a start of the conversation. I think we're going to hear a lot more about this in the future.

This is the first attempt, and I'm sure the International Hypoglycaemia Study Group, as usual, will come up with recommendations that will be useful in terms of the clinically meaningful reduction in hypoglycaemia risk.


The second session I really enjoyed was the debate on the EASD/ADA Consensus Report versus the European Cardiovascular Society (ESC) guidelines for people with diabetes. And this was with Francesco Cosentino, a cardiologist, against Peter Grant, the diabetologist.

I won't rehearse the EASD/ADA Consensus Report. We all know well about this. We have four buckets, or four layers. The first one is people with established cardiovascular disease or people with heart failure or CKD. And now it's been changed to add also, people with multiple risk factors as well. Then after that we have to look at risk of hypoglycaemia. We want to reduce weight or avoid weight gain, and finally cost as being an issue.

However, as you know, the ESC guidelines are very different. They have risks put into three levels of very high risk, high risk, and moderate risk. And moderate risk is where one would have people aged less than 50 with type 2 diabetes, aged less than 35 with type 1 diabetes, and duration of diabetes not being so long.

But he went through quite nicely, in terms of recommendations from the ESC, 138 recommendations - 50% of them being level one. And most of the discussions were around the new therapies. The exciting area we've seen in type 2 diabetes management with SGLT2 inhibitors, GLP-1 receptor agonist, and DPP4 inhibitors.

And the main argument is that they are recommending for people at very high risk and high risk to go straight on to one of these cardio-protective therapies that have been shown to improve cardiovascular outcomes, and particularly heart failure. Also, the three point MACE, and now also renal disease as well.

And he made an argument that we shouldn't be using metformin, which has been used for many, many years. It's cheap, it’s the done thing from previous guidelines, and if we don't change the paradigm, just based on all research, then we will continue doing the same thing.

And that people at very high and high risk should be initiated on SGLT2 inhibitors or GLP-1 receptor agonists.

And he gave a quite a compelling argument that DECLARE and REWIND in people with multiple risk factors, irrespective of HbA1c, we saw reductions in beneficial effects for certain outcomes.

I think we will continue this debate, but overall, my impression is that the guidelines are converging into similar recommendations. We know the ADA/EASD consensus report added the multiple risk factors following the results of the DECLARE and REWIND studies. And we've gone further with the Primary Care Diabetes Europe guidelines, or position statement, which has recommended, we should be thinking about starting combination therapy from the start, from the diagnosis.

And there is again, a great argument for this. Really good results for many, many years showing combination therapies will get people to target and they will remain on target. And we now have the VERIFY study, which also showed that early tight control with combination therapy was associated with longer-term reductions in HbA1c. And the signal - although that wasn't a primary outcome, it was one of the exploratory analysis - of a non-significant reduction in cardiovascular and MACE outcomes.

So I think over time, we will see a lot of similarities between the guidelines and position statements and recommendations than we have seen in the past, and combination therapy does seem to make a lot of sense, and it will cover all the guidelines.

Thank you very much for joining me today.


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