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In part 3 of this Exclusive Interview, John Buse talks with Diabetes in Control Publisher Steve Freed about the heart complication and amputation risks on the greater population.
John Buse, PhD, MD, is professor, chief of the Division of Endocrinology, and director of the Diabetes Center at the University of North Carolina at Chapel Hill School of Medicine.
Transcript of this video segment:
Freed: Amputation, is it a major concern? What were the findings for below-knee, lower extremity amputations and the overall study population?
Buse: So, in the overall study population there was no statistically significant difference with regards to the risk of amputations. The so-called point estimate of the hazard ratio was less than one, so the most precise estimate is that there is zero increase risk of amputations. The confidence intervals are wider, so we can’t rule out a small increase or a small decrease in the risk of amputations. And the thing that I like best about this study is it has this embedded control. So, hospitalizations for heart failure in the clinical trials, they’re reduced 40%-50%. Here in this data set, reduced about — the point estimate is reduced about 60%. So, the database works well for detecting an outcome associated with these drugs. And despite that, we weren’t able to demonstrate an issue with amputation.
Freed: And what did the subgroup analysis in patients with established cardiovascular disease show?
Buse: That’s a really important question. So, the CANVAS trial where the risk of amputation was first identified, that trial involved patients with prior cardiovascular disease. And so, we wanted to look specifically in the general US population reflected in these databases at the subset of patients who had clinical cardiovascular disease. And there was again no signal for a problem with amputations, and again evidence of a reduction in hospitalizations for heart failure.
Freed: Getting back to the amputation question, when the word came out that a particular drug in this class caused amputation, we automatically, at least the medical community assumes it’s for all the drugs in that particular classification. And the results are either a lot of physicians just hearing the word will not treat a patient with that particular drug. How do we overcome that misinformation that really affects the health of people with diabetes, and a lot of these prescriptions — just like Avandia, information came out, basically we stopped using it and now we find out that the information was wrong.
Buse: Yeah. And I wouldn’t say that the information is wrong. It just needs to be put into context. I think studies like this one where you look at millions of patients who were being treated as they are treated in the United States can provide some reassurance. And this isn’t perfect data, even though there’s large numbers of patient who are exposed to the drug. In the United States on average patients are only exposed for about six months, so many patients discontinue their drug because the insurance coverage switches or whatever. So, we don’t have a lot of patients, the data set had been exposed for two, three, four years like they were in the clinical trial. But I think physicians and patients can be reassured that at least in a real world setting there doesn’t seem to be a signal for amputations and there does seem to be a signal for those improved cardiovascular outcomes. Now, that said, I think if I had a patient who had had a prior amputation who’s at very high risk for having another one, let’s say they had lost a toe, they’re at very high risk for losing a foot or a leg, that patient would not be top of my list to use an SGLT-2 Inhibitor. And now, if they had heart failure, or something where we know the benefits are really high I might even steer them if we were going to use an SGLT-2 Inhibitor if they found this amputation question not so offputting, I might stir them to one of the agents that have not had clinical trial evidence for amputation like Empagliflozin or Dapagliflozin.
Freed: So, that brings up a good question. As a family practitioner where 90% of the type 2s go to, where should the physician go? Where do you go to get accurate information that you feel comfortable enough to take that information and put it into practice. If you put the word diabetes into Google, you get 32 million hits in about 1/10th of a second, so there’s just so much information out there right now and a lot of misinformation out there. Where should a physician go or where do you go to get accurate information?
Buse: Well, I go to the medical literature but I’m a diabetes specialist, I pretty much don’t read anything about anything unless it’s about diabetes, so I devote my life to it. It’s really complicated. And I go to my colleagues that are involved in these studies for help as well. It’s actually a great question of where the primary care provider should go to get that kind of accurate information and feel comfortable with it. The American Diabetes Association is a great resource, but their website, it’s not like they have a thing, “What would I do for a patient with neuropathy who’s had a prior amputation but has heart failure? And I think an SGLT-2 Inhibitor would be a really great drug.” There is no such resource. And frankly the best I could do or another diabetes expert could do would give you an opinion. Now, the problem is that we don’t have a lot of data with those kinds of details in them but this real world evidence over time will provide such data.
Freed: So, what were the results for hospitalization for heart failure in the overall study population?
Buse: Yeah. So, the heart failure hospitalizations with SGLT-2 Inhibitors have been well demonstrated and randomized, double-blind, placebo controlled clinical trials, so we know these drugs were for heart failure. In this study, in the database, the use of an SGLT-2 Inhibitor, Canagliflozin was the most commonly used one in the database, likewise was associated with about a, 60% is the best estimate, reduction heart failure. But basically the reason why we did it is just to see whether the database was adequate to find a signal for a benefit or a harm of the drug where we kind of knew already that there was this benefit.