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Richard Pratley Part 3, SGLT2 and TZD for Treating Diabetes

In part 3 of this Exclusive Interview, Richard Pratley talks with Diabetes in Control Publisher Steve Freed during the AACE meeting in Austin, Texas about SGLT2 and TZD for treating diabetes, and potentially more aggressive treatment of prediabetes.

Richard E. Pratley, MD serves as the Medical Director of the Florida Hospital Diabetes Institute. He is also a senior scientist at the Florida Hospital /Sanford-Burnham Translational Research Institute for Metabolism and Diabetes.

Transcript of this video segment:


Steve Freed: I have an off-label question for you. We can delete this from the video if you would like. All new drugs now have to go through cardiovascular testing because of Dr. Nissen and what happened with Avandia, even though we found out that it was incorrect. Because of him, we have a drug called SGLT-2 that’s a general category. We discovered that it can reduce your risk for death, heart attacks and strokes by more than 30%. Now we’re looking at other drugs that can do the same thing. A person with prediabetes, most of the time will progress over time to diabetes if they gain weight and become less physically active. We have drugs now that can actually provide a better quality of life for them and yet we’re very slow to recommend putting someone on SGLT-2s, even metformin, if they’re diagnosed like you said with an A1c of 6. But we’re learning that even an A1C of 5.5 can cause harm. What are your thoughts on being more aggressive?

Richard Pratley: I do agree that we should be more aggressive, but there are a number of limitations. One limitation is that we simply don’t have the evidence in the prediabetes state with a newer drugs like SGLT-2 Inhibitors and the DPP-4 inhibitors. First of all, we need to generate good clinical trial evidence. It makes sense that these drugs would work, but we need further evidence to make sure that is in fact the case. The data about the reduction in cardiovascular disease with SGLT-2 inhibitors is very important, I think, for patients with diabetes. It is important to realize that it is only benefit in patients who have pre-existing cardiovascular disease. That has been true across the different trials for CVD reduction. The people that benefit the most are the people that have the more severe disease. In part, that’s a function of the trial. We need shorter trials to be able to demonstrate that kind of benefit so we recruit higher-risk patients, but we still don’t have evidence that primary prevention with these drugs is as effective, so I think in the near future I’d like to see new trials designed which address primary prevention. That prevention could start all the way at the very earliest stage, including prediabetes. Many years ago, I ran a trial that focused on prediabetes, looking at two drugs for the treatment of prediabetes and cardiovascular disease. And while we found out that one of the drugs, Valsartan, decreased incidence diabetes a small amount, neither of the drugs was associated with the cardiovascular benefits even though the trial was well powered. So, I think we have to base our treatment decisions on evidence before we start prescribing drugs that are in many case very expensive for the large number of patients that have prediabetes.

Steve Freed: You mentioned earlier about TZDs that were one of the earlier medications, the newer medications that came out, and we saw some issues about heart attacks that was brought to our attention but a lot of information was faulty, but we don’t really hear about using a TZD even from the studies that we’ve shown that reduces the risk for getting diabetes. Why do you think that is?

Richard Pratley: I think that’s very true and I think largely that’s because these drugs have been supplanted by some of the newer agents even though they’re still very effective drugs and do have benefits as you mentioned. There is good evidence that pioglitazone can reduce risk for cardiovascular events. I participated in the trial called IRIS, which showed it was effective in reducing cardiovascular events in patients who had a stroke or TIA. It also decreased incident diabetes by 40% in that case; however, these drugs are not without their side effects. The important side effects with TZDs include weight gain, increase risk for heart failure and bone fractures. So, we have to be very careful that we’re balancing the primary prevention or even secondary prevention with the right amount of risk-taking and I think that’s one of the reasons that the TZDs have fallen out of favor is that they have profiled known side effects. Whereas some of the other drugs have a potentially more beneficial risk-benefit ratio.

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