Metformin has been the foundational therapy for patients with diabetes, particularly those with established cardiovascular disease. Yet while no large randomized trials have directly compared this long-established therapy against SGLT2 inhibitors and GLP-1 receptor agonists in first-line use, evidence exists to suggest improved cardiovascular benefit with these newer classes of drugs. In this video, James Januzzi, MD, of Massachusetts General Hospital in Boston, discusses the rationale and evidence for making such a move and touches on the cost-benefit considerations.
The following is a transcript of his remarks:
This is a question that's coming up again and again now. The reason is that given the fact that we see reductions in cardiovascular events in patients treated with SGLT2 inhibitors and GLP-1 receptor agonists, patients may actually have only enough glucose lowering needed for one drug. However, traditionally, we do start with metformin. We have no head-to-head comparisons in large-scale, randomized trials to suggest that an SGLT2 or GLP-1 should be the first-line drug, but we do have some interesting data from previously completed studies where the investigators looked at the background therapies of patients randomized to SGLT2 inhibitors. What they found was that if a patient was or was not on metformin, they still saw a reduction in cardiovascular events, particularly heart failure from SGLT2 inhibitors. What this really says is that it is a very plausible idea to start an SGLT2 inhibitor as the first-line therapy.
Now it's important to say that the American Diabetes Association does not have that in their current statement of medical care. But I can clearly envision that this might be a strategy that we'll use in the future. Of course, cost is always a consideration in our patients with cardiovascular disease. On the other hand, one might say that despite the fact that metformin is inexpensive and may itself reduce cardiovascular events, the really impressive cardiovascular risk reduction we see with the newer SGLT2 inhibitors or GLP-1 receptor agonists really tilts actually in favor of the newer drugs regardless of their higher costs.
The decision-making about how to add these new drugs, when to add them, what type of patient they should be added in, is currently being articulated in a document by the American College of Cardiology that should be published in late 2018. That hopefully should provide some guidance for clinicians, especially cardiovascular specialists, about the placement of these agents in the care of patients with cardiovascular disease.