Got questions about navigating life with diabetes? Ask D’Mine! Our weekly advice column, that is, hosted by veteran type 1 and diabetes author Wil Dubois. This week, Wil is talking prediabetes and that touchy topic of “preventing” type 2 diabetes from settling in for the long haul.

{Got your own questions? Email us at AskDMine@diabetesmine.com}

 

Peter, prediabetic from Maine, writes: I have an interest in the use of Actos and saxagliptan for treating prediabetes. Can you help? I have read your article where you say that off label use of Actos for treating prediabetes is common. Can you quantify this? Do you have the same information on saxagliptan? Also, is this a doctor-driven phenomenon, or driven by Takeda and AstraZeneca, the drugs’ makers? 

Wil@Ask D’Mine answers: Wow. Nothing on the Internet ever dies, does it? There’s no date stamp on the article you referred to, and it’s been many, many years since I’ve written for those folks — although I do see that I apparently answered a question on their website a mere seven days ago. Either I’m answering diabetes questions in my sleep (always a possibility) or they’re recycling old material and making it look new. Well, it’s theirs to recycle, but I find that a hair on the sleazy side.

That said, I re-read the short piece that you’re asking about, and it’s not gravely out of date, even though I do feel it should be in its grave by now.

Off Label Use

But on to your questions: First to off label use. Here’s the deal: Most drugs can actually do more than one thing, but it takes frreakin’ forever to get a drug approved for a single use, much less for a portfolio of uses. Meanwhile, as far as profitability goes, drugs have a short shelf life before the patent protection goes away and the Colonel’s secret recipe ends up on the Internet. All of this means there’s little motivation for the makers of drugs to pursue extra indications from the FDA, even if the makers have good reason to suspect a given med could be used for other health conditions to good effect.

Enter the doctors. They know this, too. So many docs keep a close eye on clinical research in their given fields, and if they read about a med being used to good effect for something it’s not approved for, they can choose to prescribe it off label. Off label simply means the drug is being given for a condition not listed in its approval—its “labeling.” To be clear, docs can prescribe whatever they want. Well… they used to be able to.

Enter the health insurance companies. Always looking for ways to deny coverage of things, and thus preserve their profits to the maximum degree possible, the latest trick of the insurance companies is to deny coverage for off label drugs, often under the guise of patient safety, saying something like, we care too much about you to let that nasty ol’ doctor prescribe a med for a use that the FDA hasn’t approved… Yeah. Right. Oh, as a side note, it used to be that any doc could successfully get an off-label Rx covered, then a few years ago, only specialists had any luck, and now even narrowly focused professionals are having a hard time.

All of this said, how common was off label use, back when it was easily done? Research from 2006 showed that fully 21% of all prescriptions written were off label. But as to your request that I quantify how common prescribing Actos for prediabetes was, sorry, I can’t find any data specifically on that, or even on how many diabetes meds as a class were Rx’d off label. Back when I wrote that original piece I saw it happen fairly commonly, but as noted above, the world has changed a lot since then. In fact, I’m confident that while the percentage of all off label prescribing is dramatically lower now due to lack of coverage—bearing in mind that most drugs are priced so high that if your insurance isn’t helping out, it’s doubtful you can afford to pay out of pocket for an off label treatment. I suspect that off label Actos prescribing is even more reduced. Why is that?

Well, Actos has been on a wild ride since I last wrote about it.

Which Medications Work for Prediabetes? 

After a short stint as some of the best-selling drugs in the world, the class of drugs that Actos belongs to, thiazolidinediones (TZDs), got a black eye when it came to long-term side effects, quickly tanked in popularity, and never recovered. But that aside for the moment, did they really help prediabetes? Yep. As a matter of fact there were a number of studies that showed drugs in the TZD class could delay the onset of type 2 diabetes for people who had prediabetes. Of course, most of those studies were undertaken before the fall, when TZDs were first-line drugs for diabetes. Currently, they are quasi-toxic from a liability perspective. 

Now, as to saxagliptan, that’s a whole ‘nother kettle of fish. Actos was first approved back in 1999, and saxagliptan a full decade later, when it was still owned by Bristol-Myers Squibb. The med doesn’t seem to have been studied as widely as TZDs were for prediabetes. I found evidence of two clinical trials that were recruiting in the past, but couldn’t find any results. Maybe they’re still in the works. Maybe I just missed them. Or maybe they were buried. At any rate, there doesn’t seem to be as much evidence for saxagliptan being effective against prediabetes as there was for the TZDs. And like TZDs, saxagliptan isn’t without its side effect risks, the FDA recently adding a warning to its label about heart failure risk.

The Risk-Benefit Equation

Diabetes will mess you up. Well, it has the potential to anyway, so if diabetes can be delayed—or avoided altogether—I think we can all agree that this would be a good thing. Unless the med you take to delay or avoid diabetes messes you up even worse. In which case, what have you gained? 

And that’s the crux of the problem with taking powerful meds for a developing condition that itself is merely a kitten—granted, one that will grow up someday to be a tiger. But caution is indicated here. These drugs have the potential for serious side effects. Still, that said, given the body of evidence, I think you might be able to make a case for taking Actos, so long as you don’t yet have any other cardiovascular risk factors (including a strong family history). And if your doc found some data on saxagliptan that I missed, the same holds true. But taking two meds with dark clouds in their silver linings? 

No. That I can’t see. To me, that places waaaaaaaay to much risk on the risk side of the risk-benefit teeter-totter.

And there’s one other thing to think about here. Type 2 diabetes, like diamonds, is forever. If and once you have it, it doesn’t go away. It’s also progressive, which means that even in the face of best efforts, it gets worse. Sorry, I know I’m depressing you, but there’s a reason. We know that diabetes meds generally become less effective over time. Some people believe that this is simply due to the rising strength of the diabetes over time. Others, including me, believe that the body adapts to most medicines over time, making them less and less effective. This is called medication tolerance. If I blow my shot with two diabetes meds in the first inning of the game, what will I have left in the fourth inning? In the ninth? 

Less Risky Alternatives 

Now, for what it’s worth, there’s another well-documented way to delay type 2 diabetes. It’s not risky at all, but for many people it seems to be a hard pill to swallow. Loose some weight. Want to cut your diabetes risk in half? Loose between five and ten percent of your body weight. It’s that simple (even though getting there can be challenging). 

Off Label Drivers 

And finally, to your question of who drove the dying off label craze: The docs or the drug companies? Well, first off, let’s be clear that it’s illegal for pharma companies to market their products for off label use. Unfortunately their sales teams are allowed to provide copies of medical journal articles or studies of off label use of their products. Isn’t that marketing? Apparently not, but the ice sure is thin.

And there’s no doubt that many pharma companies have abused the privilege in the past to drive sales, and some apparently still continue to do so. But let’s be clear: The drug company doesn’t write the script. The buck stops with your doctor. If your docs writes prescriptions because the pretty blonde pharma rep gave him a copy of a journal article, instead of carefully studying the science independently, then my prescription for you is to get a new doc.

 

This is not a medical advice column. We are PWDs freely and openly sharing the wisdom of our collected experiences — our been-there-done-that knowledge from the trenches. Bottom Line: You still need the guidance and care of a licensed medical professional.