SARAH: So welcome back. I am joined today by our favorite Diabetologist, Dr. Amber Healy. So Dr. Healy and I have been sitting here, we've been talking about the 2025 ADA standards of care. We were chatting about older adults and one of the topics we came across that we think is an important one to address is de-intensifying therapy. So as a pharmacist and working at the free pharmacy, I have patients come in who are on multiple medications. We have probably 10% of our patients are on 10 different medications and we understand that that is multiple chronic conditions. One we would like to talk about today though specifically is diabetes. So Dr. Healy and I have been discussing some of the medications that might be good to discuss when we talk about de-intensifying therapy. So I think what I would like to talk about, which we just had a conversation of a second ago, is we'll have patients come in and they'll be on Empagliflozin and they'll be on Metformin and they'll be on um, 

AMBER: Dulaglutide. 

SARAH: Dulaglutide. I know I'm not using my brand names. No Sarah, no Dulaglutide and they're on VALAR 150 units a day. In my head I feel like we're missing something. What are your thoughts on that? 

AMBER: That is a common trap to fall into. It's, it's comfortable, uh, to only have your patient take one or two shots of long-acting insulin like the insulin glargine. And uh, keep them on their other medications. And that's okay. We can use insulin with GLP-1s. And the biguanides and the SGLT-2 inhibitors. That's okay. But at some point a lot of basal insulin or what we like to refer to as overbasalization occurs and at some point it stops actually being helpful to the patient because you're not mimicking, uh, normal physiology. So long-acting insulin, it's like what the pancreas does when it isn't affected by uh, diabetes. It's giving you that steady little amount of insulin across the day. And that is what basal insulin mimics. And so when you up the dose, you're giving more of that, but you're not really touching what happens at mealtime. 'cause the other part of our physiology when it comes to pancreatic function is there's a sensing of, there's a hunger sensation. Your insulin level starts to go up. You eat, but your glucose level goes up and your insulin goes up to match it so you don't peak. And we lose, we don't have that in when in the diabetes, uh, you know, pathology. So you need to start giving a short acting insulin to help combat the mealtime glucose because you're missing the opportunities to decrease the glucose excursions by not ever giving the mealtime insulin. And I realize mealtime insulin is scary. 

SARAH: Yeah, I think that's the issue. 

AMBER: 'cause it's more likely to cause hypoglycemia in a short period of time. It's overwhelming. It's more injections. But at some point, even though some of these GLP-1s are fantastic and they can be given along with a long-acting insulin and you can keep these other meds on, at some point you have to recognize that you should not be just upping basal insulin if it's not working. Uh, you know, if you get to like 50 units of long-acting insulin and you're still not really getting there in combo with these other medications, it might be a good idea to start mealtime insulin. And sometimes I'll do it a little bit earlier because you need that match to look more like what your pancreas would do.

SARAH: I Love that. So that's great. That was a great discussion on over basil and maybe thinking of that 50 unit top level potentially as a number to maybe start visiting mealtime so you can mimic what's happening in your system. 

AMBER: And that's not a hard and fast rule. I mean you have to look at the person in front of you. I mean like, and if you wanna do it weight based, you know it, you might decide that 60, you know, works and then like I need mealtime insulin. But at some point you need mealtime insulin to get that other part of the insulin secretion that is not, uh, physiologic. You know, that, that we see with diabetes.

SARAH: Let's continue to talk about that, that that physiologic function of diabetes and secretagogue. So our class of secretagogues that we talk about, one of the classes is sulfonyluras is one we see commonly. Because they're inexpensive. Um, what are your thoughts on that? Continuing on that if someone's on insulin or if they're on other medications for type two diabetes? 

AMBER: Well, we have to be careful 'cause they're more likely to precipitate hypoglycemia. But the other thing that we need to keep, especially in combination with insulin. But the other thing that we need to think about is the progression of type two diabetes. It's a chronic progressive condition. Over time beta cells get tired. Beta cells don't secrete the way they did earlier on, even in type two diabetes. And when that happens, if you're giving a medication like a secretagogue where their main function is to promote insulin secretion from those beta cells, 
that drug may not be effective anymore. So sometimes like if somebody's looking to decrease their pill burden, that's the first thing I'll get rid of. I mean, If they're already on insulin, because I don't know what good it's doing them. And if someone's skeptical about getting rid of that, sometimes I'll check a c-peptide level. To you know, to demonstrate to them how much endogenous insulin their body is still producing. And you wanna actually have them hold that secretagogue before they go because you don't want to get a false result. 

SARAH: That's awesome. That's beautiful. Alright. I think the last thing that maybe we'll just discuss really quick, especially in thinking about our older adults or thinking out about patients who have had diabetes for an extended period of time, maybe especially in our type two population about renal function. And I think about some of the medications that are, that need to be monitored for renal function and whether or not those are still appropriate or if they are still working. So in my head I'm thinking of metformin or um, some of the SGLT-2 and maybe even insulin. So what are your thoughts on that? 

AMBER: Well, with metformin, it's, it's well known that when the GFR drops below 30, it's probably not a good idea to continue it 'cause you're, and you're increasing the chances of that patient having lactic acidosis. Uh, another med to think about would be even the uh, DPP-4. Like you mean Uh, you know, sitagliptin for example, like if someone has completely normal renal function A hundred milligrams is perfectly appropriate. But once that GFR drops below 50, you need to consider 50.  And below 25 you, I'm sorry, not below 25. Below 30. You'd, you might wanna be at 25, but if you go on dialysis you probably should just stop it. Uh, but then, but then you can also consider, you know, if you've got linagliptin. That is only cleared through the liver instead of the kidneys, you could alternatively keep them on that and not worry about the renal function, the renal function. If that class of medications working well for that patient. 

SARAH: Okay. That's great. 

AMBER: Uh, and then with insulin, we talked about insulin earlier. And renal function. So insulin is primarily cleared through the kidneys. So if you have a patient that's starting to have a lot of low blood sugar, a lot of hypoglycemic events and it doesn't make sense, checking the renal function and adjusting that insulin is completely appropriate because that it's hanging around longer. Uh, in the system when the kidney function starts to decline and when it's around longer, it's more likely to precipitate low blood sugar. 

SARAH: That's Awesome. And let's revisit also the SGLT-2 really quickly. Just because I know that since they're a new class, but they're seen everywhere they can be given for diabetes and heart failure. They're pretty popular right now and despite the cost, there's still a really good medication. So what are renal function limits for the SGLT-2? 

AMBER: With..it, they've been lowered over time. 

SARAH:  I know, that's what I remember, yeah they started out... 

AMBER: Because when they were introduced canagliflozin could be used, um, 60 and dapagliflozin was 60. And Empagliflozin was 45.

SARAH: It's, it always started out lower... 

AMBER: Yeah. So Empagliflozin like you can use all the way down to a GFR of 20, especially in your heart failure patients. Um, I believe the other two it's 30. So it's still pretty low. So that's a lot lower than we were at because they've been shown to slow the progression of diabetes associated kidney disease and they have their cardiac benefits. And glucose benefits. But um, it's good to be mindful of where that's a benefit to keep that medication.

SARAH: Exactly. Exactly. I really appreciate this discussion today and maybe, um, we could even talk a little more sometime about some other medications. Um, is there anything else though that you think is important to talk about when we're talking about deprescribing that you can think of right now? 

AMBER: Well, the other, I wanna call out another med just because I know that it's on the unified formulary. Okay. Um, and it's being used more now is exenatide. And because exenatide, you have to be mindful of kidney function with it as well. So the kidney function is around 30 or less. You probably shouldn't choose that GLP-1. Otherwise, we do know, I mean, most recently the FDA did just approve semaglutide for diabetes associated kidney disease after the flow trial that we talked about back in June. Uh, so that, that, that's new this week. So, you know, the GLP-1s also have their, their place in either being beneficial or something to be mindful of depending on which one you pick. 

SARAH: I love that in someone who has a renal condition. That's fantastic. Alright. We appreciate, I appreciate this discussion today. I hope everyone else does too. So this was a discussion on de-intensifying therapy and using our 2025 ADA guidelines as a basis for that. So I appreciate the discussion today. If anyone wants to check out more information, chapter 13 of the ADA a guidelines may be helpful. And so today we talked about, um, overbasalization. We talked a little bit about secretagogues and when or when those, when or when those might not be appropriate. And also about some renal function with some of our medications and hoping to maybe taking some of those medications off when they're no longer appropriate. So thank you for your time today and I'm sure that we will be back. So have a great rest of your day.