When thinking about diabetes medications, one should always consider that there are two other ways to impact blood glucose. One, and what should always be the first step in anyone's treatment regimen for type 2 diabetes, is diet and exercise. This is the easiest and arguably the cheapest way to impact one's hemoglobin A1c, which is the measure of long-term blood glucose control. and it has a few side effects and probably some really great side effects depending on your perspective. And then on the other end of the spectrum you have exogenous insulin and again this is the treatment for type 1 diabetes where you're not making insulin anymore and it also has a pretty big impact on A1C because of course it's insulin. Keep in mind that for these diabetes medications that we're going to be talking about All of them only decrease your A1C levels by about 0.5 to about 2%. And that's not a huge number. If you have someone with an A1C of about 15, and you only get them down to 13, that's not really your ultimate therapeutic goal. So you would need to get someone down either with diet and exercise, or if their pancreas has been burned out, then with some exogenous insulin with these anti-diabetes medications to help. The goal of all these medications is, of course, to lower your overall blood glucose over a long period of time. These medications differ in terms of price, in terms of side effects, in terms of mechanism of action, and it can be hard to keep them all straight, but it's nice to think of them in terms of the organs that they impact, and then how they serve to lower that blood glucose. So the oldest medication that we have is the sulfonylurea. There are first generation and second generations. An example of a first generation is chlorpropramide. An example of a second generation is glipizide or glimepiride. If this is the beta cell in your pancreas, the beta cell has these potassium channels and they're ATP dependent. What sulfonylureas do is they close these potassium channels and cause... an outflux of insulin from the beta cells. which obviously lower that blood glucose. Now these are old medications, so they're generic and very cheap. One dollar sign there. But several side effects go along with these medications. One is hypoglycemia, because you can get too much insulin in your system. One is weight gain, because you're getting glucose to actually go into your cells. and so you're gaining weight because you're getting too much glucose. And then another one is beta cell exhaustion, because you're overtaxing those beta cells by forcing insulin to pour out of them. Another medication that has a similar method of action are medications like the Meglinotide, one of the Glymides. And these are a little bit newer, so they're actually a lot more expensive, and with about the same side effect profile. Now over to the other side, looking at this, this is a liver, in case you couldn't tell. Another very popular medication right now is in the class of the big one eyes. And the mechanism of action of the big one eyes, notably metformin, is to decrease hepatic glucose production. So decreases glucose. And of course that affects your blood glucose once more. Now, these bigonides, they're also very cheap because they're generic, but it can cause diarrhea. And actually, it's contraindicated in patients with chronic kidney disease. And there is a much higher incidence of kidney disease among diabetics. So you really have to think about that when you're using metformin. There are a lot of contraindications to the medication besides this one, but that's one of the most important ones. Okay, so moving over to this muscle and this fat cell, we have the thiazolidin dions, most importantly, rosoglitazone or pioglitazone. I'm going to just mark it with a thiaz here. And these are activators of PPAR. gamma. Now what is that, you might ask? These actually increase sensitivity to insulin. And as you might recall, type 2 diabetes, one of the main problems is that your tissue cells aren't as sensitive to insulin as they used to be, and so you might have insulin available and glucose available, but the muscle cells or the fat cells just aren't very sensitive so it can't get in. But if you activate PPAR gamma, you can get insulin and therefore glucose to go into these cells and get taken up from the blood. So you get a lowering of blood glucose again. Again, one of the main side effects is weight gain. So you can think of the side effects in terms of their mechanism of action pretty easily. And these medications are also very very expensive. Over here to the gut, you have your alpha alpha. Glucosidase, glucosidase inhibitors. And the simple way to think of this is, you know, you have carbohydrates moving in to your intestines, let's say glucose. And these alpha glucosidase inhibitors block that glucose from making it out into your body. So they stay in your intestinal system rather than making it into your bloodstream and therefore, again, impacts your blood glucose. It's not hard to believe that these extra glucose can cause gas and abdominal bloating. And also some abdominal cramps and pain, kind of mildly expensive medications. But you do decrease your postprandial glucose, which is when glucose spikes tend to happen right after a meal. Now we're pretty full here, but there's one more that I want to talk about. And these are medications that impact your GLP-1, your glucagon-like peptide. So one kind of medication is GLP-1 agonist. One example is exenatide. Okay, and this acts like GLP-1, which is actually a molecule that's released after a meal. So it increases satiety, induces secretion of insulin, which again impacts your blood glucose, decreases your blood sugar by getting blood glucose into your cells again. So it has all these beneficial factors related to the release of this GLP-1 molecule. Um, One of its side effects is nausea and vomiting, and it's an inexpensive medication again. And then another one that is related to GLP-1 are your DPP-4. inhibitors. And DPP-4 is actually related to GLP-1, DPP-4, because it breaks down the GLP-1. So if you inhibit DTP-4, you have an increase in GLP-1 that has all the great factors that we just talked about. And one of the side effects of these DTP-4 inhibitors is constipation. So those are some of the important diabetes medications and I hope that helps you. Until next time!