John B. Buse, MD, PhD: In type 2 diabetes, the most common cause of death is cardiovascular death. The link is not only related to hyperglycemia, but also to underlying cardiovascular risk factors. So, type 2 diabetes is associated with insulin resistance, which is associated with hypertension, particular dyslipidemia, high triglycerides, low HDL, and small LDL particles. This phenotype is associated with increased cardiovascular risk—about 2-fold the rate of the general population.
As important as—or arguably more important than—managing glucose in patients with type 2 diabetes is managing cardiovascular risk factors. So, treatment with antihypertensive agents; treatment with lipid lowering agents, specifically statins; treatment with aspirin in the highest risk patients; and smoking cessation, etc. Cardiovascular risk reduction is arguably the most important part of diabetes management.
Two of the most important complications of diabetes medications, historically, have been hypoglycemia and weight gain. So, until the last 15 years, the medications that were available—sulfonylureas and insulin—were uniformly associated with hypoglycemia and weight gain. Most of the new drug development over the last decade has really focused on drugs that cause neither hypoglycemia nor weight gain. We have good data that hypoglycemia is a barrier, not only to physicians prescribing medications and increasing doses, but also to patients taking their medications. And weight gain is an area of tremendous focus for patients with type 2 diabetes, who are almost always overweight, and have struggled with their weight for most of their lives.
The approach that I use in working with patients to decide on the next medication to take is one of shared decision-making, where I review with patients the available options. Each has their advantages and disadvantages, and it’s remarkable how some patients have a strong feeling about one drug being better or worse for them than another. So, my approach is to generally go with the flow in that regard, obviously putting my spin on what I think are the most important issues.
With regards to deciding about a particular drug in a patient with type 2 diabetes, one of the most important new factors that we’re considering is actually cardiovascular risk. And that’s based on the recent clinical trials that have demonstrated cardiovascular benefits, using reductions in heart attack, stroke, and cardiovascular death as primary endpoints, and some drugs are even showing a benefit in death in patients with prior cardiovascular disease. So, that’s a new and important approach.