I come to you with an update on The World Championship Series for SGLT inhibitor use in T1D which just ended with empagliflozin recently being denied by the FDA advisory panel (14 no votes. 2 yes votes). This rejection follows two more losses regarding sotagliflozin and dapagliflozin – both sponsors received complete response letters (the FDA told them to go away and do all this stuff and then come back and maybe things will be different, but maybe not). Basically, a total shut out in the American League.
What’s Happening in Europe & Japan
Now in the Europe and Japanese leagues, the story is very different. The score there is 3 for 3 in the positive direction! Both sotagliflozin and dapagliflozin have been approved for type 1s with a BMI greater than 27 in Europe. (For more info on BMI/body mass index, click here). In addition, a third SGLT inhibitor has been approved in Japan with no BMI criteria. The BMI thing is a little weird and doesn’t really have a strong justification.
The FDA’s Issues
The slightly higher incidence of DKA is the only (but significant) stumbling block. This is what the FDA is hung up about, and this is why the drugs keep getting denied. We presume that the FDA is being risk averse as they want a proven risk mitigation plan such as a formal clinical trial. The FDA also does not acknowledge time in range (TIR) as a clinical endpoint when evaluating drugs for approval, which is definitely a major reason why so many type 1s love being on this medication “off label”. Only folks with type 2 are officially approved to take them.
Benefits for People with Type 1
When you look at the benefits, it is a total grand slam (to continue with our off-season baseball metaphor). Reduced A1c, improved time in range, weight loss, reduced blood pressure, and either no increase or actually a decrease in hypoglycemia. That’s not even counting all the cardiovascular and kidney benefits seen in patients with type 2 diabetes which we honestly believe have a good chance of pertaining to type 1s as well.
Finding a Happy Medium
We do still have mixed feelings about the situation. Of course we are concerned about the DKA risk, but we know these meds really help people with T1D get better control with less work. The magic combo. We honestly have many patients with type 1 diabetes who feel the beneficial effects in the first few days after starting and truly love being on them. Only a small minority of us type 1s worldwide achieve “Goal” A1c levels, so we could use some freaking help!
But there is kind of a silver lining to this recent denial by the FDA. Empagliflozin was trying to get approval for a very low dose of the medication (2.5mg) that did not have an increased risk of DKA in the clinical trials, but also did not really do enough for the FDA to approve it. A1c didn’t really change, there was only a small increase in time in range, etc- at least not anywhere near to where it changed with the higher doses. So, we can maybe take some solace in the fact that this wasn’t really the “right” way to go with these drugs. It’s not about finding a dose that’s so safe that it doesn’t freaking do anything, it’s about getting people the clinical benefits they are looking for, while figuring out how to mitigate the risk of DKA.
So what now?
Well neither of these drugs are on the shelf in Europe yet as the companies gear up to market them etc, but getting the drugs out in the “real world” will definitely help to continue to make the case here in the U.S. So the door isn’t shut for us in the states. We believe these drugs will ultimately be approved here, but the timeline is less clear. Now, you may be asking yourself, “Why do they keep talking about these drugs?” It’s a fair question. This “movement” is extremely important for us folks with type 1 diabetes. Yes, these drugs are not perfect, but they provide proof that medications other than insulin can make a real impact for individuals with T1D. If this door closes on this class of medications with clear benefits, it could really make efforts from companies, researchers, etc. shy away from this approach. Basically, we need a win and a once a day pill that can really help people is the right place to start.
So we wish you all a very happy holiday season. Enjoy your time together and eat what the hell you want but cover yourself with insulin and exercise. And if you are in Europe, please send all your SGLTi medications to:
1234 Fake Street
San Diego, CA 90210