Mark Warren, MD: When I’m evaluating a clinical trial for type 2 diabetes, I look at what the purpose of the trial was. If it’s cardiovascular outcome and cardiovascular safety, then I look at the secondary outcomes such as glycemic control, weight gain, and progression in renal disease. If I have an agent that actually can decrease cardiovascular risk and events, decrease the progression of nephropathy, have better glycemic control, and have weight loss instead of weight gain, those are all big wins. That’s important for me.
Recent cardiovascular outcome trials have been very important in determining what drugs we use for our patients. In the LEADER trial, we looked at comparing liraglutide to placebo in patients who are at high risk or who had had a cardiovascular event. There was about a 13% reduction in the composite endpoint over and beyond what we attained with conventional care, with statins, ACE inhibitors, and aspirin. So, this is over and beyond what we would expect from the statins. That’s extremely important—and an amazing finding—that we were able to improve upon the statin effect. Also, with the CANVAS trial using canagliflozin, there was also about a 14% reduction in the composite outcome, 3-point MACE, or major adverse cardiovascular events. So, it showed, with using that SGLT2 inhibitor in patients who either had an event or are at high risk for an event, that they were at lower risk with canagliflozin. They also had less progression and nephropathy in both the LEADER trial and with the canagliflozin, or the CANVAS trials. Those are very important findings that were able to show both a decrease in cardiovascular events and a decrease in the progression of nephropathy.
When evaluating the cardiovascular outcome trials, I look at what they found. Was it consistent in all the endpoints, such as with nonfatal MI, all-cause mortality, and strokes? Or, was it just in one of the areas that was it driven by, for example, strokes or heart attacks? Or, was it always consistent throughout the 3-point MACE. So, if something is more consistent across all 3 of those, that shows me it probably is more of an effect on the atherosclerotic events, and just a more consistent effect.
Looking at the cardiovascular outcomes trials, it’s important to me to look at all the results: not just the cardiovascular endpoints, but also the side effect profile and the tolerability, preferably weight loss versus weight gain and how often they’re able to maintain the medication and not stop it for fear of side effects or because of side effects.