Peter Toth, MD: GLP-1 Agonists and SGLT-2 Inhibitors for Diabetes


How some of the most recent trial analysis narrows the clinical scope of GLP-1 and SGLT-2 targeting therapies.

The introduction of glucagon-like peptide-1 (GLP-1) receptor agonists and sodium/glucose contransporter 2 (SGLT-2) inhibitors have equipped physicians with therapies possibly capable of solely managing cardiovascular and renal risks in patients with diabetes.

That said, they've been proven in pre-market clinical trials to have differing degrees of benefit, efficacy, and safety. As noted by Robert Gabbay, MD, PhD, the chief medical officer and senior vice president of the Joslin Diabetes Center, some of the controversy surrounding the 2 drug classes are their varying analogs.

In a similar discussion with MD Mag at the 2018 American Diabetes Association 78th Scientific Sessions in Orlando, FL, Peter Toth, MD, director of Preventive Cardiology, CGH Medical Center in Sterling, IL, discussed some of the most recent trial analysis and how it narrows the clinical scope of GLP-1 and SGLT-2 targeting therapies.

Peter Toth, MD: Well we've entered a remarkable period of being able to treat diabetes with extraordinary agents, but I think there are some caveats.

So, we know that not all GLP-1 agonists have met with success in prospective randomized trials. LEADER is an extraordinary study because it showed clear risk reduction using liraglutide, it reduced all-cause and cardiovascular mortality. It showed nice trends in reducing non-fatal MI (myocardial infarction) and stroke but directionally, everything moved in the right way.

And it was remarkable that there was curve separation relatively early at 12-15 months, and probably it didn't have a whole heck of a lot to do with reducing hemoglobin A1C, because we have so many drugs that do reduce hemoglobin A1C, and those trials were negative up until now, up until EMPA-REG outcomes and LEADER.

EMPA-REG outcomes — clearly using an SGLT-2 receptor inhibitor. Remarkable, the magnitude of reduction in mortality — the primary composite endpoint being reduction in heart failure — what's going on there? Well, hypotheses abound, and we're going to have to sort out how exactly it is that liraglutide and empagliflozin can provide such remarkable risk reduction so quickly when other agents have failed quite miserably.

But it's a very exciting time to be treating diabetes because it's allowed us to enter a whole new area of therapy that's efficacious, that's safe, and not only is it controlling the diabetes, but it's also reducing risk for heart cardiovascular events.

We'll see what else pops up in the years ahead. hopefully we will also see some impact on micro-angiopathy, but we'll have to see.

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