SGLT2i and GLP-1: Should It Be Prescribed for Every Atrial Fibrillation Patient?

Discussion With Bradley Knight, MD, and Andrea M Russo, MD, FACC, FHRS, FAHA

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EP LAB DIGEST. 2025;25(7):25-26.

Interview by Jodie Elrod

At the 2025 Western AFib Symposium, Bradley Knight, MD, and Andrea M Russo, MD, FACC, FHRS, FAHA, discuss use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 (GLP-1) agonists in the management of atrial fibrillation (AFib).

Bradley Knight, MD: Hi, I am Dr Brad Knight. I am excited to be joined by Andrea Russo, director of cardiac electrophysiology at Cooper, part of Rowan University, and academic chief of cardiology. Andrea, you are giving a presentation on sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists. These are glucose-modifying drugs, so why are we talking about these at an EP meeting? 

Andrea M Russo, MD, FACC, FHRS, FAHA: Thank you for inviting me. These are the drugs of the future. We are talking about them because they may have some not only favorable cardiovascular effects, but also some impact on AFib. 

Bradley Knight, MD: The SGLT2 inhibitors were studied first and were found to have cardiovascular benefits. I think the patients who want to lose weight, though, are more focused on the semaglutide-type drugs. 

Andrea M Russo, MD, FACC, FHRS, FAHA: Exactly. GLP-1 receptor agonists were approved for weight loss and we use them for diabetes. For heart failure (HF), we use SGLT2 inhibitors a lot. But for weight loss, we know that obesity has a great impact on arrhythmias, including AFib. Losing weight can help improve outcomes, and that is why our guidelines have a class I recommendation for weight loss of 10% or more for improvement of outcomes from AFib. 

Bradley Knight, MD: We know that obesity is associated with AFib and so are the secondary effects of obesity, including hypertension, diabetes (a risk factor for stroke), and sleep apnea. But what is the data that losing weight prevents AFib? 

Andrea M Russo, MD, FACC, FHRS, FAHA: Obesity is an independent risk factor for developing AFib. We have some large, randomized trials looking at the impact of some of these drugs on improving cardiovascular outcomes. They are usually composite outcomes, but they are big outcomes in terms of mortality and cardiovascular hospitalizations. So, we know that it improves that. In a lot of these studies, AFib was looked at, but as an adverse event and whether the drugs would increase the risk of AFib. It turns out that that is not the case, and in fact, if anything, there is a sign that it may actually decrease the occurrence of AFib.  

Bradley Knight, MD: Let’s talk about some patient scenarios. If you have a patient who has congestive HF but also has had a few episodes of AFib, which of these 2 drugs would you consider starting? Maybe the patient is obese as well. Do you start both or one, and how do you decide? 

Andrea M Russo, MD, FACC, FHRS, FAHA: I think you start with one. The HF specialists would probably want us to start one of the drugs that have really been shown to have a positive impact on HF, so we would probably start one of the drugs from the SGLT2 inhibitor category, and then hope that it may also have a positive impact on AFib. Again, we are talking about studies, but we have not yet had that large, randomized study looking at AFib as a primary outcome, and we need that for patients who do not have another indication for one of these drugs. With obesity, we would be starting one of the GLP-1 receptor agonists, and in that case, with the hope of improving outcomes in terms of AFib, we do not have that strong data from randomized, prospective trials that look at this as a primary outcome. We do have post-hoc analyses suggesting the beneficial effect of these drugs. It may be dependent—it may not be the whole class of drugs, and they may behave differently, but we really need to have a good study to show that. 

Bradley Knight, MD: Have the GLP-1 agonists been shown to improve HF or just weight loss? I do not see them used. 

Andrea M Russo, MD, FACC, FHRS, FAHA: I am not aware of them being studied in terms of HF outcomes. 

Bradley Knight, MD: Let’s talk about those drugs. So many patients are either on them or want to be on them. The trademark drugs are semaglutide and tirzepatide. These drugs are not identical. Some are combination drugs, and some are single drugs. If you see a patient who is very obese, has problematic AFib, and needs to lose weight, how does that conversation start with the patient who is not on these drugs? 

Andrea M Russo, MD, FACC, FHRS, FAHA: Even before these drugs became popular, when patients came in for AFib ablation or for treatment of AFib for the first time, I would talk to them about lifestyle and risk factor modification if they were obese, since a big part of treatment is losing weight. It is very important to lose weight for a lot of reasons, which we know from data from Prash Sanders and others in Australia. 

Bradley Knight, MD: If they have an ablation procedure, they are better off. 

Andrea M Russo, MD, FACC, FHRS, FAHA: They are better off by combining it with weight loss. In fact, our guidelines give us a class I recommendation for weight loss in patients with AFib. So, I would usually start there with the conversation of lifestyle modification and importance of weight loss. Plus, some patients are obese and if they have not already had the conversation with their primary care physician (PCP) about potentially considering one of these drugs, I would bring that up to them. Semaglutide is often the one that is utilized for that purpose. 

Bradley Knight, MD: It is a tough topic. For me, it falls in the same category, much like sleep apnea. What is the role of the electrophysiologist here? I personally do not prescribe these drugs to patients, but I have EP colleagues who do. There are also the implications of what happens if you do prescribe it. How do you approach this? Do you suggest they go back to their PCP? 

Andrea M Russo, MD, FACC, FHRS, FAHA: I agree, I do not actually prescribe it myself—we subspecialize. It is not just about the drug—weight loss is a team effort. It is a whole team approach that may include losing weight, increasing activity levels, and involving a dietician to maintain a healthy lifestyle for the long term. So, it takes a team. And while I do not prescribe the drugs, we often do. 

Bradley Knight, MD: Some of our colleagues will do their own ordering for sleep apnea screening, and so they get a little more involved. Medicine has changed—it used to be that PCPs would refer patients to you. Now, patients often come directly to subspecialists and have cut out their PCP, who they may not have seen for a couple of years. It is difficult to put the patient in the middle of that. So, there also maybe seems to be a lack of awareness in the PCP community of how important weight management is in patients with AFib. 

Andrea M Russo, MD, FACC, FHRS, FAHA: We have a team that was originally built by our bariatric surgery department. Not every patient needs to have bariatric surgery, but the team includes a dietician. So, if you have something like that at your center or could develop something similar, it kind of takes us off the hook of prescribing the drugs. Again, there may be some other things that we do not know. For example, if the patient has diabetes, someone else must be managing that, not just us. 

Bradley Knight, MD: What are the obstacles that you see? There are side effects. There are older patients who get sarcopenia. There are some trade-offs of weight loss, particularly with these drugs. There is also cost and availability, and certain criteria that the insurance companies cover. Do you have patients who come to you and say that the drugs sound great, but they have tried and cannot get them? 

Andrea M Russo, MD, FACC, FHRS, FAHA: That happens a lot. Maybe this is more of an issue in the United States than other places, but the drugs are expensive and some of the payers do not cover it. There are some specific weight loss centers where I know people go, so that is a big challenge. 

Bradley Knight, MD: Does Medicare cover these drugs? Most people have Medicare Advantage, so I think it may be specific to their coverage plan. 

Andrea M Russo, MD, FACC, FHRS, FAHA: Yes, I am not sure which of the payers do and do not, but I know they often have a hard time. 

Bradley Knight, MD: Yes. I think that the United States Food and Drug Administration had deemed these drugs to be in a national shortage, which allowed people to have different pathways to get them through these compounding pharmacies. It was recently announced that there was no longer a national shortage of these drugs. Has that had any impact on your patients’ access to these drugs? 

Andrea M Russo, MD, FACC, FHRS, FAHA: Yes, I think that is great. It is one step to have availability of the drug, but patients still need to be able to afford and pay for them. So, I still think cost is an issue for many patients in regard to access. Hopefully that will change as time goes on.

Bradley Knight, MD: When patients are referred to me or come to me specifically for an ablation procedure, it is difficult to know at what point to say that we will do the ablation. They have tried weight loss drugs and all these other things. For me, another consideration is the risk of the procedure. I think the risk of the procedure in obese patients has been shown to be equal, but if you had a major complication in the EP lab, a patient who is over 300 pounds would be very difficult to manage. Do you ever have that issue with patients? 

Andrea M Russo, MD, FACC, FHRS, FAHA: Yes. I have had the same thought process too. Plus, in terms of long-term and recurrence rates, I want to have the best outcomes. Obviously, we all want to have the best outcomes for our procedures. So, to have a patient lose weight before the procedure would be ideal. 

Bradley Knight, MD: If I have agreed to do the procedure, but it is not scheduled for another 3 months, I will tell the patient to try to lose weight beforehand, since they will be better off in the long term. So, it is a very important topic. This is a rapidly moving field, and there is probably a lot more data that we need. Is there anything else that you would like to highlight? 

Andrea M Russo, MD, FACC, FHRS, FAHA: I think that we are starting to get there and in different populations of patients. For example, in the peri-ablation cohort, I think we have a lot of data suggesting that this will be beneficial, including from the post-hoc analyses looking prospectively at which drugs, how long to treat for, whether there are category-specific effects, and at what doses. We need to better understand the mechanisms. We think it is more than just the weight loss; we think there is also some potential impact that could be on AFib from a variety of other mechanisms. So, I think it is just the beginning and it is an exciting time.

Bradley Knight, MD: It is an exciting and critical topic. Thanks for doing this. 

Andrea M Russo, MD, FACC, FHRS, FAHA: Thank you! 

The transcripts have been edited for clarity and length.