Hello. I am Eduard Montanya. I am professor of medicine at the University of Barcelona and a clinical endocrinologist attending patients at Bellvitge Hospital. In the next 10 minutes, I will discuss with you the potential role of GLP-1 receptor agonists in clinical practice. My disclosures, and in the past 20 years, since the publication of the U.K. PDS basically, the management of type 2 diabetes has been predominantly glossocentric. This is something that has changed in the very recent years due to the availability of new treatments for patients with diabetes and also to the results of the cardiovascular outcome trials and the new guidelines that have been released in the last three, four years, and that have been continuously updated have moved towards a more personalized and cardiovascular risk focused approach. A very nice example is the position statement that the American Diabetes Association and the European Association for the study of diabetes released in 2018. In 2019, those guidelines were updated and what they establish right now is that the first line therapy continues to be Metformin, but that immediately when we start the treatment of patients, we have to consider whether there are indicators of high risk or established cardiovascular disease or chronic kidney disease or heart failure. If this is the case, then the recommendation is to consider the use of a GLP-1 receptor agonist or an SGLT-2 inhibitor independently of baseline like in the modeling of the patient, or the individualized, like the model of in target. Therefore, if patients have this high risk or established already cardiovascular disease, chronic kidney disease or heart failure, but the atherosclerotic cardiovascular disease predominates that the recommendation is that to use a GLP-1 receptor agonist with proven cardiovascular benefit. An SGLT-2 inhibitor without proven cardiovascular benefit, if the GFR is adequate, is also recommended, but considering the very strong data that we have that shows the particular benefit of GLP-1 receptor agonists with MACE, the measure adverse cardiovascular event, are the main concern for that patient, it seems that the GLP-1 receptor agonist may offer an additional benefit and this is a comment that has been included in this updated consensus report of the ADA/EASD in 2019. For those patients that have heart failure or chronic kidney disease, particularly those with a reduced ejection fraction, of less than 45-percent or with chronic kidney disease with a GFR between 30 and 60 or an increase albumin/creatinine ratio, then it's clear that the strong evidence is in favor of the use of an SGLT-2 inhibitor. Nevertheless, if the SGLT-2 inhibitor is not tolerated or is contraindicated, then the recommendation is again to use a GLP-1 receptor agonist with proven cardiovascular benefit. These are the recommendations of the ADA and the EASD. The European Society of Cardiologists in the most recent update of its guidelines has quite a similar approach. For those patients that are already on Metformin and that have atherosclerotic cardiovascular disease are at high risk or at very high risk, then the recommendation is to use also a GLP-1 receptor agonist or an SGLT-2 inhibitor and if for those patients that are drug naive, here there is a slight difference with the recommendation of the ADA, the EASD, because the ESC has gone a step farther in their recommendation of an SGLT-2 inhibitor or a GLP-1 receptor agonist, even in monotherapy, before Metformin and regardless of glycated hemoglobin. For those patients that are a lower risk, a lower cardiovascular risk, then the recommendation of the ESC is to use a GLP-1 receptor agonist at different stages of the intensification of the glucose management. The American College of Cardiologists have released also an updated version of its consensus decision pathway in which basically they also recommend the use of an SGLT-2 inhibitor or a GLP-1 receptor agonist with proven cardiovascular benefit to treat patients that are at high risk for cardiovascular disease or they already have established atherosclerotic cardiovascular disease or heart failure or chronic kidney disease. But then we have those patients without established cardiovascular disease or without heart failure or chronic kidney disease or that are at high risk. In this case, the recommendation is again to start with Metformin, but then to intensify the treatment according to the glycated hemoglobin of the patient. So, if the glycated hemoglobin is not on target, then we take a portionalized approach in which you consider the risk of hypoglycemia, the weight management of the patient, the cost of the medication and based on that, we individualize the intensification of patients. For instance, when there is a compelling need to minimize hypoglycemia, and I think for instance about elderly patients or those patients for which having a hypoglycemia when they are working may be of a particular risk of those patients that have hypoglycemic unawareness, then the recommendation is to use a treatment that it's not increasing the risk of hypoglycemia and the GLP-1 receptor agonist are clearly one of the recommended options, as they are, when we have to intensify the treatment with patients that are already on some other medication. If weight is the concern, and they wonder when the weight, the body weight is not a concern for patients with type 2 diabetes, then the recommendation is to use a GLP-1 receptor agonist with good efficacy for weight loss and there is a stratification of the benefit that we can achieve with the different GLP-1 receptor agonist. Semaglutide is the treatment, the molecule that has shown the higher benefit in reducing body weight and then it goes to liraglutide, dulaglutide, exenatide, or lixisenatide, so they are recommending when there is a compelling need to minimize weight gain or promote weight loss, again the SGLT-2 inhibitors can also be used and if those patients are down on SGLT-2 inhibitor still remain with a glycogen model that is above target, then the recommendation is to consider the addition of a GLP-1 receptor agonist, again, considering which one of them has the higher efficacy for weight loss. Clearly, GLP-1 receptor agonists or the SGLT-2 inhibitors are not the first option when cost is a major issue for the particular patient. There is a final scenario in which the GLP-1 receptor agonists are also recommended and this is when we plan to intensify the treatment of patients using injectable therapies because now the recommendation is to consider a GLP-1 receptor agonist in most patients prior to the use of insulin, and for those that are already on insulin, if we have to increase the treatment to intensify the treatment, with the addition of new therapies in order to keep the glycogen model under control, then the recommendation is again to use a GLP-1 receptor agonist prior to the intensification with multiple additional doses of insulin, of rapid acting insulin. So, if I may summarize, so for people with high risk of cardiovascular disease or already established atherosclerotic cardiovascular disease, chronic kidney disease or heart failure, when should we consider the initiation of a GLP-1 receptor agonist always one of those with proven cardiovascular benefit? Well, first it is important to remember that now we do that independently of glycated hemoglobin and we consider that in patients that have type 2 diabetes and indications of high risk, any of them with high risk for cardiovascular disease or already established cardiovascular disease, kidney disease or heart failure, and particularly in those patients where the atherosclerotic cardiovascular disease is predominate. Also, for those patients that have already type 2 diabetes and have developed an event of cardiovascular disease, then the reverse situation, those patients that already have type 2 diabetes and that develop atherosclerotic cardiovascular disease, and finally, at hospital discharge, after an admission for a cardiovascular event, or even for a diabetes related event, that is a very pertinent place where we have to consider the addition of a GLP-1 receptor agonist. Then, we have those patients without high risk or clinical atherosclerotic cardiovascular disease, chronic kidney disease or heart failure, in those patients, we are going to consider the addition of a GLP-1 receptor agonist when the glycated hemoglobin is above the individualized target and there is compelling need to minimize hypoglycemia, there is a compelling need to minimize weight gain or promote weight loss, or also when we plan to intensify the injectable therapy or intensify those patients that are already on basal insulin therapy with another injectable. And with this, I thank you for your attention.
This educational video is part of a series called '5 Things a cardiologist needs to know about GLP-1 RA' that are aimed to guide cardiologists in management of patients with type 2 diabetes, since the cardiology practice is increasingly confronted with these patients. This series covers five topics that help cardiologists understand why GLP-1 RAs are promising as multifactorial treatment for patients with T2D and/or obesity and CVD, and to improve clinical implementation of guidelines recommending treatment with anti-diabetic drugs with CV benefit.
Prof. Eduard Montanya, MD - Bellvitge University Hospital, University of Barcelona, Spain
This recording was developed under auspices of PACE-cme. Views expressed in the recording are those of the presenter and do not necessarily reflect the views of PACE-cme.
Funding for this educational program was provided by an unrestricted educational grant from Novo Nordisk A/S.
The information and data provided in this program were updated and correct at the time of the program development, but may be subject to change.
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