For U.S. Healthcare Professionals Only


The Glycemic Explorer Challenge – Test Your Knowledge

How does each therapeutic class affect various organ systems?

Test your knowledge on the various type 2 diabetes treatment classes as they light up before your eyes in this dynamic, fast-paced video.

Title: Physiologic Abnormalities in T2DM

Welcome to the Glycemic Explorer Challenge series! I’m Dr. Helen Baron your host—and a clinical and academic endocrinologist. I’ll be challenging you on your knowledge of the complexities in type 2 diabetes and using a virtual tool to see how different therapeutic classes target the various organ systems affected by the disease.

We all know that in type 2 diabetes, there is insulin resistance and insulin deficiency.

But we’ve also come to know that type 2 diabetes is a complex disease that involves multiple physiologic abnormalities and that addressing hyperglycemia may involve an approach that targets different pathways. So let’s take a minute to explore how the different therapeutic classes affect the different organ systems.

Here on the left, we have various organs and tissues involved in hyperglycemia.

On the right, we have several classes of antihyperglycemic medications.

I’m now going to test your knowledge of which organ systems are affected by which medication.

Let’s start with DPP-4 inhibitors. Which organ systems do you think these affect?

The pancreatic β-cells, α-cells, and liver.

How about GLP-1 RAs?

The pancreatic β-cells, α-cells, GI tract, brain, and liver.

And which organ systems does insulin affect?

α-cells, liver, muscle, and adipose cell.

And metformin?

The liver.

Next we have SGLT-2 inhibitors, and these have an effect on….
…the kidney.

Sulfonylureas have an effect on which organ system?

The pancreatic β-cells.

And finally, which organ systems do you think TZDs affect?

The liver, muscle, and adipose cell.

Now let’s consider how using some of these treatment classes in combination may address the various pathophysiologic abnormalities of type 2 diabetes. Remember, ADA and AACE guidelines recommend combinations of oral therapies and combinations of injectable therapies that address different pathways in patients not achieving their HbA1C targets. Options for therapies in combination often involve metformin plus one or more additional classes of medication.

So let’s take a look at some therapies that are typically used together and how they affect these organs and tissues.

As we saw previously, metformin impacts the liver. By adding insulin, you can see that the α-cells, adipose cells, and muscle are also affected.

Once again, metformin on its own affects the liver.

And by adding a GLP-1 RA, we also affect the GI tract, brain, pancreatic β -cells, and α-cells.

Now let’s take a look at metformin...combined with a DPP-4 inhibitor.

Now take a look at metformin...... combined with a GLP-1 RA.... and sulfonylurea.

And here we see metformin…....with insulin……. as well as sulfonylurea.

You’ll notice that combining multiple therapeutic classes allows you to target multiple organ systems. So, in conclusion, in appropriate patients, an approach that addresses multiple physiologic abnormalities of type 2 diabetes may include combining therapies that target different pathways.

So for your patients not achieving their A1C targets, ask yourself, will your next move do enough?

Thanks for joining us. Look for more chances to challenge yourself with the other videos in this series.

Discover more here at