Quantifying the Potential Impact of SGLT-2 Inhibitors in Heart Failure - Episode 16

Interest Regarding Diabetes and CVD Risk

Darren K. McGuire, MD, MHSc, discusses his interest in assessing the connection between diabetes and its cardiovascular complications and reinforces why it is so important for stakeholders to understand the relationship and study further.


Darren K. McGuire, MD, MHSc: It’s important for physicians and providers to understand the connection between Type 2 diabetes and heart failure. I’ve been working in the diabetes and cardiology space for over 20 years, and for the first 15 years of that, we were really focused as a cardiology and endocrinology community on the atherosclerotic cardiovascular disease [ASCVD] risk associated with Type 2 diabetes.

We realized there was some heart failure risk; it’s only been within the last 5 to 7 years that we’ve understood the critical importance of considering heart failure as 1 of the cardiovascular complications of Type 2 diabetes.

This has been driven by better epidemiology, and partially driven by our improvements in outcomes for ASCVD, which have allowed the heart failure signal to rise to a point where the likelihood of people with Type 2 diabetes having a heart attack is similar to that of heart failure. It’s risen to a high level of population prevalence in the patients with Type 2 diabetes. Now we have some medical therapies that mitigate overall cardiovascular risk, but the SGLT2 inhibitors specifically have a potent effect on both the risk for developing heart failure and the treatment of heart failure. This has answered the conversation where we are considering heart failure at the same intensity as we do for atherosclerotic cardiovascular disease.

Early in my career in cardiology, I decided as a second-year resident that I was going to focus on diabetes and its cardiovascular complications. That was driven exclusively by the complete lack of evidence that we had for cardiovascular risk regarding outcome efficacy and safety. We didn’t even know if the available medications were safe. At that time, the only medications we had available were insulin and sulfonylureas. Soon thereafter, around 1995, metformin came online. We had very little information, other than the glycemic effects of these medications. What were their longer-term consequences for cardiovascular and other clinically important outcomes?

It was an accident that I got interested in this. I chose a topic for a grand rounds-type presentation called ischemic preconditioning. I thought when I picked the topic, I’d be talking about how ischemia induces new blood vessel formation in the heart and how we could get around ischemia by forming new blood vessels. It turns out that this ischemic preconditioning phenomenon is a molecular entity mediated by the ATP-dependent potassium channels. That is important because it is exactly the target of action of sulfonylurea medications that block the ATP-dependent potassium channel.

The question arose whether blocking this cardiac-protective mechanism with the medicine we’re commonly using for hyperglycemia might be deleterious. I embarked on my career to try to explore the sulfonylureas and ideally, as we’ve done over a 20-year effort, build an evidence basis so we know drugs are at least safe. Ideally, as we discovered, some can be incrementally beneficial from a cardiovascular perspective.