John B. Buse, MD, PhD: In 2008, when the FDA came out with their guidance on cardiovascular outcome trials being required to have a drug approved for management of type 2 diabetes, the focus was entirely on safety. And it was based on an observation that perhaps some drugs that nearly became marketed actually produced cardiovascular harms.
Since then, we have not had any of the drugs demonstrated provide cardiovascular harms, but we had the surprising occurrence of a straightforward cardiovascular benefit with relatively short exposures around 3 years in patients at very high cardiovascular risk, where you think of cardiovascular disease being very well established.
The FDA had this guidance with pharmaceutical companies. I do think we need guidance now from medical societies, and we need guidance from pharmacy benefits managers, insurers, and payers. If we now have evidence that diabetes drugs are associated with reductions in heart attack, stroke, and death, we really should be using these drugs in patients at high cardiovascular risk.
I think it’s actually a scandal that probably less than 10% of patients with a prior heart attack, stroke, bypass, or stents—people at high cardiovascular risk, who would have qualified for these studies—are treated with SGLT2 inhibitors or GLP-1 receptor agonists. And that’s just wrong. If we take the time, spend the money, and engage patients in doing these trials—and there have now been more than 100,000 patients engaged in these trials—we ought to make sure that patients reap the benefits of that research and are exposed to these drugs in the routine management of diabetes.
I think it’s absolutely essential we make sure that for every insurance plan in America, however we need to make it happen, patients at high risk for cardiovascular events—those with prior heart attacks, strokes, cardiovascular procedures, or multiple risk factors with evidence of end-organ damage—should have access to GLP-1 receptor agonists and SGLT2 inhibitors that have demonstrated proven benefit in reducing cardiovascular endpoints.
There has been a lot of talk about how the current FDA guidance on doing these cardiovascular outcome trials has really reduced the enthusiasm of the pharmaceutical industry to develop diabetes drugs, because of the high cost of doing these trials. I hope that the marketplace rewards these companies by shifting therapy towards these agents and that more companies develop additional diabetes drugs targeting mechanisms that have the promise to potentially reduce cardiovascular risk factors and cardiovascular events. We’ve had an explosion in diabetes drug development since the mid-1990s. So, until 1994 in the United States, we only had 2 classes of drugs: insulin and sulfonylureas. And since then, we’ve had about another 10 classes of drugs added to our toolbox for managing diabetes.
There are some promising things on the horizon, but not as many as I’d like to see now. And in particular, some of these small companies are struggling to find major partners that are willing to invest in these new classes of medications. So, my hope is that these recent wins will pay off and, as a result, there’ll be greater investment in new drug developments in diabetes.