Dr Rudolf de Boer on SGLT2 Inhibitor Success Across Disease States

Among the beneficial effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors are their ability to lower blood pressure and promote weight loss, with newer lab-based studies showing their ability to normalize metabolic abnormalities, stated Rudolf de Boer, MD, PhD, clinical cardiologist and professor of translational cardiology, University Medical Center Groningen, the Netherlands.

Transcript

Why have SGLT2 inhibitors seen such success across several disease states, in particular heart failure, type 2 diabetes, and chronic kidney disease?

That’s an interesting question. We're still not fully aware of how exactly the drugs exert their beneficial effects. On the other hand, it's not so uncommon for cardiovascular drugs to be beneficial in heart disease, in renal disease, and in diabetes. We, of course, are seeing similar trends with RAAS [renin-angiotensin-aldosterone system] inhibitors, the ACE [angiotensin-converting enzyme] inhibitors, the ARBs [angiotensin receptor blockers], the mineralocorticoid receptor antagonists. Also, for example, lipid-lowering drugs, such as statins, have been proven beneficial in patients who are at risk for heart disease, who have prevalent heart disease, patients with diabetes. Clearly, several pathomechanisms are shared when it comes to heart disease, renal disease, and diabetes.

In more detail, we know that SGLT2 inhibitors exert various effects, including blood pressure–lowering effects. Although they're not strong antihypertensives, they do lower blood pressure. They are associated with weight loss— not dramatic weight loss, but on average patients lose several kilograms—and, more recently, there's also been mechanistic studies in the laboratory setting showing that they have certain beneficial effects.

For example, organ metabolism, where they normalize metabolic abnormalities that are common in heart and kidney disease. They, for example, foster the utilization of certain substrates, including ketones and other substrates, where there are shifts in the disease toward certain substrates that necessarily aren't beneficial—so they are normalized by the use of SGLT2 inhibitors.

I think these are very elegant drugs. They don't push particularly hard on one disease mechanism going wrong. What they do is they normalize a number of parameters in a rather subtle manner, and I think that explains their clear efficacy on one side but also their very favorable safety profile on the other hand.