How are these medications helping my diabetes?


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The following transcript has been edited for length and clarity.

Ginger Vieira: Welcome to Collab Conversations with the American Diabetes Association and Beyond Type 1. My name is Ginger Vieira and today we are talking to Dr. Ruth Weinstock, president of medicine and science at the American Diabetes Association.

Dr. Weinstock, thank you for joining us.

Dr. Ruth Weinstock: Thank you for having me.

Today we are going to pick our brain about the many diabetes medications that are on the market today and how they work, how they help you lower your blood sugar levels. There are so many, Dr. Weinstock, where do we start? What’s the first one most people are introduced to when they’re diagnosed with type 2.

We usually start with the tried and true metformin, which is generic, inexpensive, has been around for decades and we know it’s safe and effective. So that is usually the first one that we try. But depending upon the level of blood glucose, as well as whether individuals have certain other conditions such as heart failure or kidney problems, we might start two medications at the time of diagnosis. It depends.

Also, if the individual is very symptomatic from high blood sugars, losing weight unintentionally, urinating a lot, being very thirsty with very high blood sugar levels, then we might start with insulin initially. With type 2 diabetes, that doesn’t mean that the individual will always need insulin, unlike type 1. But if the blood sugars are that high and the individual is very symptomatic, then insulin treatment would be used to help normalize and then try to transition to non-insulin therapy if possible.

To get things down quickly, because they’re at a high enough level that it’s more dangerous to gradually come down.

We used to have, many many years ago, one basic algorithm, you start with this drug, then you go to that drug. We don’t do that anymore. We now personalize therapy. We individualize therapy depending upon the age, the range of blood glucose readings, blood sugar readings, the presence of other conditions.

There are certain diabetes medications that can also help if you have kidney disease, or help with weight-loss and so on. Some are in pill-form, some are daily injections, or once-a-week injections.

So again, depending on the situation, I think we try to personalize it and find the best possible medication for that individual because insulin, for example, people tend to gain weight. So if we can control the diabetes and get the levels where we want with the once-a-week injectable and metformin, let’s say, that does not cause weight-gain but actually helps them lose weight and we can control the diabetes. Then that’s great.

The cost of a medication is also a factor…

Yes, the other consideration is the cost. So these SGLT2 inhibitors and these GLP1 receptor agonists that I mentioned are expensive. They’re new. They work very well, but some people can’t afford them, which is sad. One of the things we’re trying to do with the American Diabetes Association (ADA) is working to ensure that everybody who needs certain medications, that they’re affordable and accessible to them so that they can stay healthy. But unfortunately right now that’s not the case for many people, they’re in high deductible plans or have high copays or they don’t have insurance for a variety of reasons.

So in those cases we don’t want to prescribe something that they can’t afford and then they don’t take it or they ration it and so it doesn’t work well. So that’s defeating the purpose. If a patient truly can’t afford other options, there’s an older drug—sulfonylureas—that are also extremely inexpensive, just as metformin is extremely inexpensive. It works very well at lowering blood glucose levels. And so that may be something that would be used in somebody who’s having trouble affording their medications.

So, going back to metformin, could you tell me the gist of how it helps lower blood sugars?

So metformin works in several ways, but the main way is on the liver. So in type 2 diabetes, for many individuals, the liver, when you’re sleeping, particularly overnight, makes too much sugar. It actually manufactures glucose and metformin helps suppress that so you don’t wake up with high blood sugars. That’s one of the main ways that it works.

Okay. And then SGLT2 inhibitors. How do those help lower blood sugar levels? 

So normally the kidney, when your blood sugar is high, it filters glucose and then reabsorbs, it brings it back into the body and this, these drugs block that reabsorption. So you basically eliminate some of that sugar through your urine. So as you urinate, there’s more sugar in it and you get rid of it through that mechanism. That’s the main way that they work.

Okay. And then we have the GLP-1 agonists.

The GLP-1 receptor agonist, that’s a very interesting class of drugs. So it turns out that when you eat, when your GI tract and your intestines see the nutrients from the food, it signals the pancreas to secrete extra insulin. So if I gave you glucose directly into your blood versus eating it, pancreas would squirt out extra insulin when that food went through your intestines. Normally, there is a rise in this hormone called GLP-1 that’s stimulated when you eat.

So there are certain cells in your intestines that secrete a very short lived hormone called GLP-1 that causes the pancreas to squirt out extra insulin in response to eating. It also suppresses a hormone called glucagon that works the opposite of insulin. Glucagon raises blood sugar and can make you feel a little fuller by slowing your digestion a bit, which also helps with weight loss.

So in people with type 2 diabetes, many of them are deficient in this hormone. And so this injectable GLP-1 receptor agonist, actually is also now available in a pill form, that basically is replacing the GLP-1 that you’re deficient in.

Okay. So those are the first three categories.

And then the sulfonylurea drugs, which have been around a very long time, they’re available in generic options, and they directly stimulate the pancreas to squirt out extras.

But unlike the GLP-1s, it’s a more constant increase in insulin production.

They are a longer acting, and so sulfonylurea drugs, if you take too much of them—particularly elderly people are more prone to this—your blood sugar can go too low, which is what we call hypoglycemia. Whereas that is not common with the GLP-1 receptor agonist. Also, sulfonylureas are weight neutral or cause a little bit of weight gain, whereas the GLP-1 receptor agonist, because of those other effects on feeling full and on the stomach and on glucagon actually usually causes weight loss.

And would DPP4 inhibitors be the next of the top five?

The DPP4 inhibitors. So I mentioned the GLP-1. That’s the hormone that when you eat food, the nutrients in your digestive system, in your intestines, cause those cells in your intestines to squirt out GLP-1, that hormone, which is short-lived and causes the pancreas to secrete some extra insulin. It turns out that your native GLP-1, the GLP-1 that your body normally makes has a very very short half life that after just a very very short period of time, a few minutes, it is metabolized. It’s degraded by an enzyme called DPP4.

So what this pill does, the DPP4 inhibitors, is it partially prevents your native, the the GLP-1 that you make yourself from breaking down that fast. So they can raise those levels. You don’t get as high levels as with the injectable GLP-1 receptor agonist, but they’re safe. They’re not associated with hypoglycemia, low blood sugars, usually. And they’re usually pretty well tolerated. They don’t lower the A1C as much and they don’t cause weight loss, but they also don’t cause weight gain.

Okay. And it’s important for someone to know that if one type of diabetes medication in a certain drug class isn’t working for them for whatever reason, side-effects or it’s just not helping their blood sugars come into range, they should talk to their doctor about trying something else.

Absolutely. So as we learn more about diabetes and more and more research is done, what we now call type 2 diabetes is going to end up being multiple types of diabetes. Because again, we know it’s very heterogeneous, and I predict in the future, there’ll be a blood test that’ll say, you need a GLP-1. And you won’t need that, in fact that won’t even work on you, you should use metformin. And for someone else, metformin won’t work, so you should use this. So I think we’ll be able to personalize it based on what the genetics and the actual type of diabetes that that individual has. But right now we don’t have that knowledge and we don’t have those tests. So the best we can do right now is start with what makes the most sense.

But if your blood sugar levels are not at goal, you should add something else. If the drug you’re on didn’t make a difference, your blood sugars didn’t change when you started that drug and now you’re on it and you’re taking it, then stop that drug and try a different one. If it did help, then maybe you need another drug on top of it. So different people are going to respond in different ways. And all of that needs to be discussed with the healthcare provider.

It gets very complex because there are so many wonderful choices we have now with more and more coming up in the future, including more and more insulins. So if you have tried all the non-insulin therapies and you’re still not at goal, you might require insulin therapy.

Okay. That’s really valuable to know that they all work so differently. So if one is not working, it’s not that all these meds are useless, it’s that you haven’t found the right one that’s really addressing the right issue, that could help you.

Right. And checking your blood sugar often with a blood glucose meter or a continuous glucose monitor is really important. We can’t know if your medications are working well if we don’t know what your blood sugar is.

Thank you so much for that very high level, but simplified explanation of all of the options on the market today.

My pleasure.

WRITTEN BY Ginger Vieira, POSTED 12/09/21, UPDATED 10/11/22

Ginger Vieira is an author and writer living with type 1 diabetes, celiac disease, fibromyalgia and hypothyroidism. She’s authored a variety of books, including “When I Go Low” (for kids), “Pregnancy with Type 1 Diabetes,” and “Dealing with Diabetes Burnout.” Before joining Beyond Type 1 as digital content manager, Ginger wrote for Diabetes Mine, Healthline, T1D Exchange, Diabetes Strong and more! In her free time, she is jumping rope, scootering with her daughters, or walking with her handsome fella and their dog.