Zachary T. Bloomgarden, MD, MACE: We have a number of drugs that treat multiple conditions, usually as an off-target manifestation of the action of an agent. For example, I mentioned that the SGLT2 (sodium-glucose cotransporter-2) inhibitors appear to be particularly beneficial in reducing heart failure. Why might this be the case? Well, individuals with diabetes overexpress the glucose transporter, SGLT2, in the renal tubules. This leads to increased resorption of sodium and to decreased delivery of sodium to or past the loop of Henle to the macula densa. In a certain sense, the renin-angiotensin-aldosterone system of people with diabetes perceives a volume-contracted state and then causes a hyperreninemic elevated aldosterone condition which may potentiate the development of heart failure.
With this perspective, we could say that the SGLT2 inhibitors may have dual benefit, both in terms of reducing blood pressure and as diuretics, or as ACE (angiotensin converting enzyme) or ARB (angiotensin II receptor blocker) potentiators in directly benefitting cardiovascular function. So, there’s been a huge amount of interest following the EMPA-REG trial in trying to understand this and then ask, “Okay, should we use these drugs preferentially in individuals with heart failure?”
As I mentioned, [should] the bile acid sequestrants [be used]? These drugs (bile acid sequestrants) were developed as LDL (low-density lipoprotein) [cholesterol]-lowering agents. They’re modestly effective, but they also lower blood sugar and reduce A1C (glycated hemoglobin) by about 0.5%. Individuals with diabetes clearly are benefitted by both having an agent that lowers LDL cholesterol and an agent that lowers hemoglobin A1C—another area where a single drug works in multiple fashions, and there are a number of other examples.
In general, this is a delightful add-on that one thinks of as an extra benefit, but we should bear in mind that we have a primary reason for using a given drug. Empagliflozin should primarily be given as a diabetes drug, for example. Secondarily, we will be very happy if we accrue additional benefits for a given individual.