EASD ADA consensus guidelines on type 2 diabetes
18m | Sep 10, 2022Episode: EASD ADA consensus guidelines on the overall approach in glucose lowering medication in type 2 diabetes
This podcast is intended for healthcare professionals. My name is Fernando Florido and I am a GP in the United Kingdom. In this episode I go through the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) consensus guidelines on the overall approach in glucose lowering medication in type 2 diabetes. I will firstly give you a list of the changes to the previous consensus recommendations followed by a description of the consensus recommendations flowchart on the subject. The original article was published on 19 December 2019 with a subsequent correction published on 15 May 2020.
There is a YouTube version of this episode in the NICE GP YouTube Channel that you can access here:
· https://www.youtube.com/channel/UClrwFDI15W5uH3uRGuzoovw
This episode also appears in the
Primary Care guidelines podcast:
· Redcircle: https://redcircle.com/shows/primary-care-guidelines
· Spotify: https://open.spotify.com/show/5BmqS0Ol16oQ7Kr1WYzupK
· Apple podcasts: https://podcasts.apple.com/gb/podcast/primary-care-guidelines/id1608821148
Diabetes in Primary Care podcast:
· Redcircle: https://redcircle.com/shows/diabetes-in-primary-care
· Spotify: https://open.spotify.com/show/5BmqS0Ol16oQ7Kr1WYzupK
· Apple podcasts: https://podcasts.apple.com/us/podcast/diabetes-in-primary-care/id1562910252
The ADA-EASD consensus guidelines can be found here:
· Website:
o https://link.springer.com/article/10.1007/s00125-019-05039-w
· Or download here:
o https://1drv.ms/b/s!AiVFJ_Uoigq0lW-4rilnP_mruV41?e=FjPLGo
The Summary of the changes to the previous consensus recommendations can be
· Viewed on website above:
o https://link.springer.com/article/10.1007/s00125-019-05039-w
· Or downloaded here:
o https://1drv.ms/b/s!AiVFJ_Uoigq0lW72FZuzZZiv8bPr?e=7Fib8M
The Visual summary “glucose lowering medication in type 2 diabetes- overall approach” can be found here:
· Website:
· Or download here:
o https://1drv.ms/u/s!AiVFJ_Uoigq0lXCNFscGYei60BiV?e=3n0Ern
Intro / outro music: Track: Halfway Through — Broke In Summer [Audio Library Release]
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Transcript:
This podcast is intended for healthcare professionals. Thank you for listening and welcome to a new episode, bringing you medical information and clinical guidance from a primary care perspective. My name is Fernando Florido and I am a GP in the United Kingdom.
In today’s episode I am going to go through the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) consensus guidelines on the overall approach in glucose lowering medication in type 2 diabetes.
I will firstly give you a list of the changes to the previous recommendations followed by a description of the consensus recommendations flow chart.
If you have been following previous episodes, you may be familiar with the updated NICE guidelines on the management of type 2 diabetes. However, the NICE recommendations, primarily followed in the UK, have some substantial differences when compared to other international recommendations and this is why I have decided to do this episode today. You will notice that the main difference with NICE refers to the use of GLP1 mimetics which NICE considers to be less cost effective. However, from a clinical perspective, there is now ample evidence in their favour, which justifies a wider use as described in the consensus guidelines.
I will put in the description below a link to download the full article as well as the summary of the changes and the flow chart. There is a YouTube version of this episode and other NICE guidance on the NICE GP YouTube Channel and a link to access it can be found in the podcast description. Because of the visual nature of the flow chart, I would highly recommend watching the YouTube video if you can.
Although describing visual aids as audio files can be challenging, I hope that you find the content clear and informative.
Right, let’s go right in. So, we are going to start looking at the European Association for the Study of Diabetes and the American Diabetes Association consensus guidelines on managing hyperglycemia in type 2 diabetes, published in December 2019, corrected in May 2020 and I have put links in to it in the episode description.
Now, before starting the treatment flow chart, we are going to go through the changes to the consensus recommendations and this is just a brief summary of what the changes are.
As a general consideration we will say that, in high-risk patients, the decision to treat with a GLP 1 receptor agonist or an SGLT 2 inhibitor should be considered independently of the HbA1c. This is because these agents have been proven to reduce major adverse cardiovascular events, hospitalisation for heart failure, cardiovascular deaths and CKD progression.
We will say that in patients with established atherosclerotic cardiovascular disease, the level of evidence for cardiovascular benefit is greatest for GLP 1 receptor agonist and this is in terms of reducing major adverse cardiovascular events.
And because of this, to reduce the risk of cardiovascular disease, the GLP 1 receptor agonists can also be considered in patients who have no cardiovascular disease but who are at high risk of cardiovascular disease.
For patients with heart failure, especially if their heart failure has a reduced ejection fraction, that is, an ejection fraction less than 45%, or if they have CKD with an eGFR between 30 and 60 and microalbuminuria, with urine albumin creatinine ratio greater than 30 particularly if it is greater than 300, the level of evidence is greatest for SGLT 2 inhibitors. So, SGLT 2 inhibitors are recommended with patients with heart failure and equally the SGLT 2 inhibitors are recommended for patients we CKD to prevent progression of CKD as well as the cardiovascular outcomes.
Obviously, because there is a link between SGLT 2 inhibitors and an increased risk of amputation, patients with foot ulcers or at high risk of amputation, should only be treated with SGLT 2 inhibitors after careful shared decision making around the risks and benefits and with comprehensive education and foot care and amputation prevention.
Well, that was the summary of the changes. Now we are going to dive in straight into the flow chart, which is titled: “glucose lowering medication in type 2 diabetes: overall approach”. And in the right top corner there is a note that tells us that, to avoid clinical inertia, we need to review the patients regularly, ideally every three or six months.
Now, the first thing that the flow chart tells us is that the first line therapy is always metformin and comprehensive lifestyle including weight management and physical activity. So, metformin first of all, and then, we are going to see if there are indicators of high risk or established atherosclerotic cardiovascular disease, CKD or heart failure. If the patient has any of these, then we will consider independently of the HbA1c the treatment.
This side of the flow chart then divides in two, one if cardiovascular disease predominates or, two, if heart failure or CKD predominate.
So, if atherosclerotic cardiovascular disease predominates, either because there is established cardiovascular disease or there are indicators of high risk for getting cardiovascular disease, then we will preferably give a GLP 1 receptor agonist with proven cardiovascular disease benefit and the chart tells us at the bottom in the notes that proven cardiovascular benefit means that it has a label indication for reducing cardiovascular events.
If you cannot give or do not want to give a GLP 1 receptor agonist then we will give an SGLT 2 inhibitor with proving cardiovascular benefit, as long as the eGFR is adequate. And again, it reminds us at the bottom of the chart that we have to be aware that SGLT 2 inhibitor labelling varies by region and individual agents with regard to the indicated level of eGFR for initiation and continued use.
Right, so we repeat again, independently of the HbA1c and if cardiovascular disease predominates, we will give either GLP 1 receptor agonist or an SGLT 2 inhibitor.
And then, we will look at the HbA1c and if the HbA1c remains above the target then we will consider further intensification of the treatment.
For patients who are on GLP 1 receptor agonists we will give an SGLT 2 inhibitor and, likewise, if they had initiated an SGLT 2 inhibitor then we will give them a GLP 1 receptor agonist. As an alternative, we can give a DPP 4 inhibitor if the patient is not on a GLP 1 receptor agonist, and this is because of their mode of action or we can also give basal insulin, pioglitazone or a sulphonylurea. So, we are just going to mix and match those agents, always preferably starting with GLP 1 receptor agonist, then SGLT 2 inhibitors and then we can give a DPP 4 inhibitor if the patient is not on a GLP 1 receptor agonist, or basal insulin, pioglitazone or a sulphonylurea.
And, also in the notes at the bottom, it tells us that degludec and U 100 glargine have demonstrated cardiovascular disease safety. It also tells us that a low dose of pioglitazone may be better tolerated though less well studied for cardiovascular effects and, in terms of sulphonylureas, it reminds us that we should choose later generations of sulphonylureas to lower the risk of hypoglycaemia and glimepiride has shown similar cardiovascular safety to the DPP 4 inhibitors.
So, that concludes the section where cardiovascular disease predominates. Now if heart failure or CKD predominate, particularly if it is reduced ejection fraction heart failure or if CKD has an eGFR between 30 and 60 and microalbuminuria at least 30mg per gram or more, we will use preferably an SGLT 2 inhibitor with evidence of reducing heart failure and / or CKD progression in cardiovascular outcome trials, as long as the EGFR is adequate.
So, it tells us in the notes at the bottom that both empaglifozin and canaglifozin have shown reduction in heart failure and also reduced CKD progression in cardiovascular outcome trials. Canaglifozin has primary renal outcome data from CREDENCE and dapaglifozin has primary heart failure outcome from the DAPA HF trial. But all these details may be becoming less and less relevant because it is now increasingly thought that the SGLT 2 inhibitors have a class effect.
Now if an SGLT 2 inhibitor is not tolerated or contraindicated or if the eGFR is less than adequate, we will give a GLP 1 receptor agonist with proven cardiovascular benefit.
So, it is more or the other way round from the cardiovascular disease branch. There we gave a GLP 1 receptor agonist first and then an SGLT 2 inhibitor. Here, in heart failure of CKD we are going to give an SGLT 2 inhibitor first and then GLP 1 receptor agonist second.
And, again, we need to remember that if a patient has heart failure or CKD, we will consider this treatment with an SGLT2 inhibitor or a GLP 1 receptor agonist independently of the HbA1c.
And then, we will look at the HbA1c, and if the HbA1c is above the target, we will consider further treatment.
The first thing that we have to consider is that we need to avoid pioglitazone in the setting of heart failure because it tends to worsen it because of fluid retention. We will try to stick to agents with cardiovascular safety. So, for patients on an SGLT 2 inhibitor, we will consider a GLP 1 receptor agonist. Or we can give a DPP 4 inhibitor but not saxagliptin in the setting of heart failure, as long as the patient is not on a GLP 1 receptor agonist. Alternatively, we can give basal insulin or a sulphonylurea.
So, in summary, after an SGLT 2 inhibitor and a GLP 1 receptor agonist, if we need to give anymore drugs, we will avoid pioglitazone and saxagliptin in in the setting of heart failure. We can consider a DPP 4 inhibitor, if not on a GLP 1 receptor agonist, or basal insulin or a sulphonylurea.
Right, this ends the branch of heart failure or CKD patients. So, we have now covered both if a patient has got atherosclerotic cardiovascular disease, heart failure or CKD. However, if a patient has not got those conditions and they are not at high risk of those conditions, then we will give metformin and then will be guided by the HbA1c in order to decide whether to give more treatment.
And we will divide this treatment in three, depending on whether, one, we want to minimise hypoglycaemia, two, we want to minimise weight gain or promote weight loss and, three, when cost of treatment is a major issue. So again, we divide the treatment on whether we focus on hypoglycaemia, on weight or on cost.
Firstly, we will look at the branch where minimising hypoglycaemia is our priority. And for those patients, we will use any of the agents that are not associated with hypoglycaemia. That is, a DPP 4 inhibitor, a GLP 1 receptor agonist, an SGLT 2 inhibitor or pioglitazone. So, we give dual therapy with metformin and one of those drugs. If the HbA1c remains above target then we will give triple therapy with metformin and any combination of the drugs already mentioned, a DPP 4 inhibitor, a GLP 1 receptor agonist, an SGLT 2 inhibitor or pioglitazone bearing in mind that we must not combine a GLP 1 receptor agonist and a DPP 4 inhibitor. But all other combinations are allowed.
And then, if the HbA1c remains above target on triple therapy, we will continue with additions of other agents so we can go to quadruple therapy.
Finally, if the HbA1c remains above target. Then we will consider the addition of a sulphonylurea or basal insulin. And with sulphonylureas we will choose the later generations with lower risk of hypoglycaemia such as glimepiride or we will consider a basal insulin with lower risk of hypoglycaemia. And there is a small note at the bottom of the chart that tells us that the insulin with lowest risk of hypoglycaemia is degludec and glargine U300, followed by glargine U100 and detemir, followed by finally NPH insulin.
Now, the second branch is when we are going to focus on the weight because we need to minimise weight gain or promote weight loss. In these cases, we will give either at GLP 1 receptor agonist or an SGLT 2 inhibitor because both these agents are associated with weight loss. And a small note at the bottom of the chart tells us the GLP 1 receptor agonists with good efficacy for weight loss. The best one is semaglutide, followed by liraglutide, then dulaglutide, then exenatide and finally lixisenatide. So, if we can, we will give them always either semaglutide or liraglutide.
And then if the HbA1c remains above target then we will give the second of those two agents, so, if the patient is had a GLP 1 receptor agonist, we will give an SGLT 2 inhibitor and if they have had an SGLT 2 inhibitor then we will give in GLP 1 receptor agonist.
And if the HbA1c remains above target, then we will start quadruple therapy because the patient would already be on metformin, a GLP 1 receptor agonist and an SGLT 2 inhibitor. But if this combination is not tolerated or contraindicated, then the lowest risk of weight gain is with a DPP 4 inhibitor and this is because the DPP 4 inhibitors have got weight neutrality, but that can only be given if the patient is not already on a GLP 1 receptor agonist.
If the DPP 4 inhibitor is not tolerated or contraindicated or if the patient is already on a GLP 1 receptor agonist, we should use cautiously a sulphonylurea, pioglitazone or basal insulin, and this is because all these agents are associated with weight gain.
Finally, the last branch of the flowchart is when we are going to focus on the cost, because cost is a major issue. And there is a note at the bottom of the page that is going to tell us when we should consider cost to be a major issue. Therefore, cost should be our focus if there are no specific comorbidities, that is, no established cardiovascular disease, there is a low risk of hypoglycaemia and weight is not a real concern.
Also, there is a warning in terms of cost, saying that we need to consider country and region-specific cost of drugs because, in some countries for example, pioglitazone can be relatively more expensive and a DPP 4 inhibitor relatively cheaper.
So, looking at the flowchart, if cost is a concern, after metformin we will start with either a sulphonylurea or pioglitazone, which are generally the cheapest agents and if the HbA1c is above target, we will go into triple therapy with metformin, a sulphonylurea and pioglitazone. And if the HbA1c remains above target, then we will consider either insulin therapy, giving basal insulin with the lowest acquisition cost or we can consider a DPP 4 inhibitors or an SGLT 2 inhibitors with the lowest acquisition cost. Or, in other words, we go into quadruple therapy according to whatever is the most cost-effective combination.
Right, this is it, we have completed the review of the EASD ADA consensus guidelines flow chart. So, this is the end of this video and the summary of the consensus recommendations. There is also a YouTube version of this episode in the NICE GP YouTube Channel and I will leave a link in the episode description. Thank you for listening and I hope that you will join me in the next one.
