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Rick, type 1 from Massachusetts, writes: Wil, a lot of attention recently has been devoted to the Pros and Cons of type 2 GLP-1 and SGLT-2 medications being added “off label” as an adjunct therapy for persons with type 1 diabetes. What I haven’t read is whether it’s believed the cardio-protective effects seen with T2s on these meds might also help type 1 tickers. What do we know (or speculate) so far?

Wil@Ask D’Mine answers: We know a fair bit, actually, although as you’ll soon see, it may not be much help to us. But before we get into that, it’s worth relating the story of the discovery of the cardio-protective effects of these two classes of meds.

Following the unexpected discovery during the landmark ACCORD trial that the TZD class of drugs might actually increase increase the risk of heart attacks, in 2008 the FDA mandated cardiovascular outcomes trials to be included in the approval process for all new diabetes medications. This newly required deep-dive into cardiovascular outcomes struck gold for some pharma companies when it unexpectedly turned out that two new classes of blood sugar meds not only did no harm to the heart, but might actually help the heart! These were GLP-1s and SGLT-2s, and the discovery eventually led to new care guidelines, moving these agents to a position near the top of the treatment pyramid for T2s.

Now, I should point out that these drugs are not created equal in this regard. When it comes to the GLPs, studies show mixed results, with some studies showing the GLP-1s help the heart, while other studies suggest this drug has a neutral effect. Meanwhile, the data on SGLT-2s is pretty much a slam dunk that they are good for the heart.

Fascinatingly, in both cases, even though we can see the positive effect, no one is quite sure how the meds help the heart—although some new research suggests they reduce aortic plaque, independent of cholesterol levels or body weight, and also reduce inflammation.

So, all of that said, what do we know specifically about T1 tickers and this pair of T2 meds?

What few studies there are on the use of GLP-1s in T1s have produced conflicting results. While they sure work for lowering blood sugar, the evidence for helping out with the heart is less clear. It is worth mentioning that some research shows this drug class extends a cardio-protective effect to both T2s and non-diabetic patients, so it seems safe to assume it could benefit our hearts, too.

Still, there’s not much to go on. Actually, Novo Nordisk—makers of Victoza, one of the leading GLP-1 drugs—decided a few years ago not to seek approval for that drug for type 1s, citing weak evidence for its overall effectiveness in our kind.

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For people with type 1 diabetes who already have heart conditions, SGLT-2 drugs seem to help prevent heart attacks.

By comparison, more is known about SGLT-2 use in T1s, and the drugs seem to carry the same benefit for our hearts as they do for the hearts of others—but at much greater risk in another area. More on that in a minute. But first, just how good are SGLT-2 meds for the ticker?

The latest data suggests that taking an SGLT-2 med can reduce the risk of a “major cardiac event” by a whopping 11%. Various studies, however, show that this benefit is largely seen in people who already have cardiovascular disease (CVD). For folks who don’t yet have heart conditions, it seems to make no real difference in risk.

So perhaps these meds are more cardio-curing than “cardio-protective.”

Of course, virtually all the studies to date are in people with T2, which makes sense as the SGLT-2 meds are approved for treating T2. That said, what little research there has been so far in T1 diabetes seems to support the idea that SGLT-2s do help T1 hearts just as much as they do T2 hearts — which is to say the most help comes in those who need it most: people with diabetes who already have CVD.

But the lack of T1 data is sure to change quickly, as one SGLT-2 has already been approved for use in T1s in Japan, and two others have been approved for T1s in Europe.

Now, about that additional risk I mentioned: While the SGLT-2s help with blood sugar in T1s, and can help with ailing hearts, they also have an unusual and dangerous side effect for T1s—they lower the blood glucose threshold for diabetic keto acidosis (DKA). That means DKA can set in at lower BG levels, and strike faster, without some of the usual warning signs we expect — sometimes even at only mildly elevated glucose levels.

The FDA has even issued a “black box” warning about the unusual properties of DKA with this class of medication. And in a recent article in the journal Diabetes Care, Drs. Joseph Wolfsdorf and Robert Ratner urge physicians to use “extreme caution” when considering SGLT-2s for the treatment of type 1 diabetes. The authors further suggest that regular monitoring of blood ketones, rather than blood glucose, is needed for T1s using SGLT-2s.

That said, a debate session at this year’s American Diabetes Association annual Scientific Sessions, showed that the vast majority of doctors support using SGLT-2s off-label for T1s, despite the risks.

Certainly, if you have CVD, and can afford blood ketone testing (the strips aren’t generally covered by insurance and are roughly twice the cost of glucose test strips at almost two bucks a strip), an SGLT-2 med could be a game-changer.

But if your ticker is ticking just fine for now, and with no evidence (yet) that SGLT-2 meds provide help to a healthy heart, the risk doesn’t seem worth the benefit, IMHO.


Wil Dubois lives with type 1 diabetes and is the author of five books on the illness, including “Taming The Tiger” and “Beyond Fingersticks.” He spent many years helping treat patients at a rural medical center in New Mexico. An aviation enthusiast, Wil lives in Las Vegas, NM, with his wife and son, and one too many cats.