Dr Deepak Bhatt on the Potential Stroke Benefits of SGLT1s

The reduction in stroke and myocardial infarction seen in the SCORED trial is probably indicative of a benefit specific to the sodium-glucose cotransporter-1 (SGLT1) inhibitor class, said Deepak L. Bhatt, MD, MPH, executive director of interventional cardiovascular programs at Brigham and Women’s Hospital Heart & Vascular Center and professor of medicine at Harvard Medical School.

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We have not seen a stroke benefit in the sodium-glucose cotransporter-2 (SGLT2) class. If an SGLT1 is creating a stroke benefit, is there the potential that patients with diabetes may only have to take 1 drug as opposed to an SGLT2 and glucagon-like peptide-1 receptor agonist (GLP-1 RA) to reap the stroke benefits?

With sotagliflozin, possibly because of the SGLT1, there was a significant reduction in both stroke and myocardial infarction (MI) in the SCORED trial. It's also possible that we had a large number of patients with diabetes and chronic kidney disease and lowish glomerular filtration rate (GFR), and it was that combination that allowed that benefit to be evident, and maybe other trials, if they targeted that type of population, the SGLT2 inhibitors may have also shown reductions in stroke and even MI. That is something we can't say for sure. But right now, I guess, my feeling is it's probably an SGLT1-specific benefit. I can't say we proved that in these trials, because there was no other SGLT2 inhibitor with sotagliflozin vs placebo. So, I can't say with absolute certainty, of course, but a potential differentiating feature of this drug.

Now in terms of GLP-1 RA, that's another terrific class of drugs just like SGLT2 inhibitors. Putting cost aside, I think there's a lot of complementary benefits between those 2 classes of agents. We saw some data even here at the American Diabetes Association from other programs where it does appear that the two provide additive clinical benefit, certainly additive benefit with respect to glycemic control. So again, putting the cost issue aside, I think many patients with diabetes would be well served by being on both an SGLT2 inhibitor and a GLP-1 RA because, in real life, many times patients with diabetes will need more than one drug anyway on top of dietary intervention and so forth.

I don't really see it as an either/or. I think in an ideal world where cost isn't being considered, using both would be in the patient's best interest. Now, in the real world, of course, both are expensive and using them both together could leave the patient with pretty high co-pays, depending on their exact insurance. Another sort of situation, would, potentially, having sotagliflozin obviate the need for GLP-1 RA? I don't know. I think that is something that would need to be studied before I would go that far. But certainly, the potential for sotagliflozin to reduce both heart failure–related events—as all the SGLT2 inhibitors seem to do—and atherosclerotic events, as has not been quite so evident for the SGLT2 inhibitor class as a whole, that potentially could make it a really desirable first-line drug.

But, again, that all depends on whether the drug gets approved, what the labeling is, what the pricing of sotagliflozin might be. There are a lot of “ifs” that would need to be answered before I could directly address your question. But for the time being, I'd say if it is financially possible for the patient, for many patients with diabetes being on both an SGLT2 inhibitor and a GLP-1 RA would probably provide the most overall cardiovascular, heart failure, and kidney protection that is possible, and certainly seems to exceed what any of the older diabetes drugs do. I mean, obviously, most of those are generic and cheap, that's the advantage. But the disadvantage is they, in general, don't have cardiovascular outcome data supporting their use. And when they do, it's sort of like with metformin, kind of older data, small number of patients, or in the case of some other agents, a little bit more mixed. So, again, if the costs weren't an issue, these newer diabetes drugs just have such a wealth of cardiovascular outcome data and other safety data, that I think they ought to be preferred.