FAQ: Why would I consider an incretin over a sulfonylurea, which has been known for over 50 years to promote insulin secretion by the beta cells?

Frequently asked questions for the primary care community, excerpted from a conversation between a leading primary care physician and a world-renowned beta cell researcher. (1:15)


Dr. Leahy: One of the major flaws of sulfonylureas is they act on a signaling pathway, which is an icon channel right on the beta cell membrane -- right really at the distal stages of insulin secretion and so they bypass all of the important intracellular beta cell biology which makes that cell glucose responsive.  So normally that cell is incredibly precise at regulating insulin secretion to the prevailing glucose concentration.  Good if your sugar is high, even better if your sugar is low because it turns off insulin secretion. 

The problem is that sulfonylurea kind of loses that.  And so you can give this drug and promote more insulin secretion than you would want when blood sugars are pretty normal, or frankly, low.  And so that’s been one of the downsides of those drugs for years -- a risk of hypoglycemia.  And with the incretin system the concept was well this is an important intracellular system, which is also glucose responsive and maybe these drugs will preserve glucose responsiveness and they do.  And so one of the benefits that is superior to the sulfonylureas is a considerably lower risk of hypoglycemia.  So that’s the reason I think we move in to try to use biology to create new drugs and the newest ones we have are incretins that brings some interesting benefits.