John Anderson, MD: There are a lot of factors to consider when you’re looking at trying to choose the right medication for a patient. We always go back to diet and exercise. It’s still the number 1 recommended treatment for type 2 diabetes. And then, of course, metformin is still the number 1 recommendation both from the American Diabetes Association as well as the American Association of Clinical Endocrinologists. About 15% to 20% of our patient population in the United States can’t tolerate metformin no matter what you do, so there are patients who you’re going to have to use something else for as first-line therapy if they can’t tolerate it.
And then, you have a range of options from oral agents to injectables to even the use of insulin after metformin. So, how do you make that decision? It largely depends upon the patient sitting in front of you. How old is this patient? Do I need to worry more about safety in an elderly, frail patient who has had cardiovascular disease? Or is this a young man who’s going to have diabetes for the next 40 years and I want to use an aggressive approach? How far from baseline are they? Is this someone with a very high baseline A1C? Is this someone with a low A1C? How much efficacy is there? How much A1C lowering do I need from that medication?
The other thing is, is this a person, like many of our patients with type 2 diabetes, who struggles with weight? There are medications. There are both injectables and oral agents that will actually help with weight reduction. Some of these same agents will actually help with lowering blood pressure. And we go back to safety. Is this an agent, like insulin, or a secretagogue, like a sulfonylurea, that can cause hypoglycemia? In some patients, that’s an acceptable side effect because they can tolerate it. In other patients—the more fragile patients, those with cardiovascular disease—that might be something you want to avoid.
What are the other comorbidities? Because we now have agents that have shown not just glycemic lowering, and not just weight reduction, and not just systolic blood pressure reduction. We now have agents in 2 different classes that have also shown actual cardiovascular outcomes benefits. So, in patients with cardiovascular disease and diabetes, there’s a whole new way of thinking about how you select that next medication.
Another thing that might play into the role of what medication you’re going to choose has to do with hypoglycemia. Some patients are at significant risk for hypoglycemia, and there has been some evidence that hypoglycemic patients with cardiovascular disease can lead to worsening outcomes. The other thing is that some of these agents can also cause weight gain. Our TZDs [thiazolidinediones], our sulfonylureas, have the potential for weight gain, sometimes a little bit or sometimes a little more. With some patients, you really want to avoid that. And so, again, that goes into how you think about these medications.
For a long time, we thought about dysglycemia as the Holy Grail in treating patients with type 2 diabetes. And we had that thought because of type 1 diabetes in the DCCT trial and the UKPDS trial for patients with type 2. But most patients with type 2 diabetes die of cardiovascular disease, overwhelmingly. Patients with diabetes are at a 2- to 4-fold increased risk of cardiovascular disease: That is, heart attack, stroke, and cardiovascular death. In addition, we’re learning more that type 2 diabetes is a huge risk factor for congestive heart failure. So, when we treat patients with diabetes now, we think about dysglycemia: That is lowering their risk for microvascular disease, retinopathy, neuropathy, and nephropathy. But we also think about lowering risk for cardiovascular disease. That’s why it’s compelling with new cardiovascular outcomes trials that perhaps there are agents that are more beneficial than others in terms of lowering that risk.