Dr Aung Myat (Brighton and Sussex University Hospitals NHS Trust & Brighton and Sussex Medical School, Brighton, UK) discusses new antidiabetic drugs and the management of diabetic patients through primary and secondary prevention.
Filmed in London at BCIS ACI 2020.
Interviewer: Mirjam Boros
Videographer: Natascha Wienand / Dominic Woodruff
Transcript Below :
Question 1 : What are the new anti-diabetic drugs ?
The main drugs that have been seen to not only control diabetes and sort of have an effect on glycemic control but also, have been shown to have cardiovascular benefit are the GLP-1 receptor agonists and the SGLT2 inhibitors. So clearly, both classes of drugs don't automatically roll off the tongue but certainly, they have been in use for a while now by our diabetology colleagues and the focus of my lecture really was to prompt the interventional community, to start thinking about these drugs because they are widely available, they are easy to prescribe, they have fairly few side effects or contraindications and they have a huge amount of evidence base behind them, essentially.
Question 2 : Can you summarise the key CV outcomes reported with these agents ?
It all really started in 2007, when there were issues with a drug called rosiglitazone. That drug was an excellent glycemic-control drug but there was evidence that it was causing an excess of cardiovascular events, especially myocardial infarction and heart failure. Because of that, it prompted the US Food and Drug Administration in 2008 to basically order all new diabetes drugs coming onto the market to have adequately-controlled, -sized cardiovascular outcomes trials, essentially. And really, these trials were designed to test the safety of these new diabetic drugs. Now, they all succeeded in doing that, each of these trials, particularly the LEADER trial, the EMPA-REG OUTCOME trial, CANVAS, DECLARE-TIMI 58, they were big trials, so, because they had to be to show safety and conclusively prove it so we're talking at least three and a half thousand up to seven or eight thousand patients randomised and the patients that were randomised all had diabetes and all had either established cardiovascular disease or were at high or very high risk of, or had very high cardiovascular risk, essentially. So, they're the kind of population that we as intervention cardiologists see every day and they proved safety but also, unexpectedly, showed that these drugs also have cardiovascular benefit, both in terms of sort of major adverse events and in particular, with empagliflozin and liraglutide, they showed actual mortality benefit. So, this is evidence really that we can't ignore.
Question 3 : Are there differences in efficacy between diabetic patients vs non-diabetic patients ?
It's difficult to say, certainly with the GLP-1 receptor agonists, they have a very low risk of hypoglycemia because the endogenous enzyme GLP-1 stops acting once basal plasma glucose levels return to normal. Obviously, if you add the GLP-1 receptor agonist to another anti-diabetic drug, you will get the risk of hypoglycemia from the other anti-diabetic drug but because they have a low risk of hypoglycemia, they have been tested in non-diabetic individuals and they have been shown to be safe in non-diabetic individuals and also precipitate significant weight loss in non-diabetic individuals so actually, liraglutide, in particular, has FDA approval as a weight loss drug.
Question 4 : What special considerations should be taken with patients on these agents in the cath lab ?
Unfortunately, the title of the talk was wrong, in some respects, because we don't really use these drugs in the cath lab. The focus of the talk was actually, we should be using these drugs before a patient gets to the cath lab, i.e. prevention. And also, after the patient has been to the cath lab and again, prevention, but this time, in the secondary arena. So, it was really focusing on trying to treat these diabetes patients who are at high cardiovascular risk more holistically. So, we as interventional cardiologists should start looking beyond simply checking whether a patient's on metformin so we don't cause any sort of nephropathy and you know, beyond, you know, prescribing sliding scales for patients who have hyperglycemia when they come in with an acute chronic syndrome. We should be taking the first steps, certainly in type-2 diabetic patients who don't get regular secondary care follow-up, who are maybe seen by a practise nurse at their GP but that's about all they get, in terms of surveillance of their diabetes. We as interventional cardiologists should be taking an active role in sort of beginning the conversation, with regards to these patients being on these newer types of drugs.
Question 5 : What proportion of the patients taking these agents would you expect to encounter in the future ?
The size of the problem, with regards to diabetes, isn't going to get any smaller. It's estimated that up to four million people in the UK, three and a half million with diagnosed and about half a million with undiagnosed diabetes are currently in existence. By 2025, it's estimated that there will be over five million diabetics in the UK alone and over 600 million worldwide. So, it's not a problem that's going to go away and certainly, now that we have guidelines issued by the European Society of Cardiology and associated with the European Association of the Study of Diabetes and we have now this wealth of evidence, involving literally thousands of patients, we don't really have any excuses anymore not to be prescribing these types of drugs to our diabetes patients. And you know, effectively, from our point of view, in the cath lab, we may see, perhaps, one takotsubo patient a month, we may see spontaneous coronary artery dissection once every three months, once every six months but we see diabetes patients every day so they're there, they need to be treated properly and we need to either instigate primary prevention or secondary prevention for them.