GLP-1 Agonists: Clinical Conundrums

Listen in as our expert panel tackles real-world questions about GLP-1 agonists, from starting them and setting expectations with patients to strategies for switching agents. You’ll also hear them review key considerations to limit muscle loss with GLP-1 agonist use and discuss why some patients hit a plateau or don’t respond to GLP-1 agonists.

Special guests:

• Jennifer N. Clements, PharmD, FCCP, FADCES, BCPS, BCACP, CDCES, BC-ADM
  • Clinical Professor and Director of Pharmacy Education
  • University of South Carolina College of Pharmacy
• Jennifer M. Trujillo, PharmD, BCPS, FCCP, CDCES, BC-ADM
  • Professor and the Associate Dean for Education
  • University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences

Panelists on TRC’s Editorial Advisory Board:

• Stephen Carek, MD, CAQSM, DipABLM
  • Clinical Associate Professor of Family Medicine
  • Prisma Health/USC-SOMG Family Medicine Residency Program
  • USC School of Medicine Greenville
• Craig D. Williams, PharmD, FNLA, BCPS
  • Clinical Professor of Pharmacy Practice
  • Oregon Health and Science University

For the purposes of disclosure Dr. Jennifer Clements reports relevant financial relationships with Novo Nordisk (Ozempic, Rybelsus), Eli Lilly (Zepbound, tirzepatide) [speakers bureau].

The other speakers have nothing to disclose.  All relevant financial relationships have been mitigated.

This podcast is an excerpt from one of TRC’s monthly live CE webinars, the full webinar originally aired in February 2026.

 🏷️ Use code mt1026 at checkout for 10% off. 

TRC Healthcare offers CE credit for this podcast. Log in to your Pharmacist’s Letter, Pharmacy Technician’s Letter,or Prescriber Insights account and look for the title of this podcast in the list of available CE courses.

Claim Credit

Clinical Resources:

• Comparison of GLP-1 and GIP/GLP-1 Receptor Agonists
• GLP-1 and GIP/GLP-1 Receptor Agonist Interactive Comparison Chart
• Comparison of Weight Loss Products
• Improving Diabetes Outcomes
• Diabetes Medications: Cardiovascular and Kidney Impact

Email us: ContactUs@trchealthcare.com.

The content of this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment.

Find the show on YouTube by searching for ‘TRC Healthcare’ or clicking here.

Learn more about our product offerings at trchealthcare.com.

Transcript

This transcript is automatically generated. 

00:00:07 Stephen Carek

I had a patient that came in with a bottle that said GLP-1 on it in big letters.

00:00:13 Stephen Carek

What it was some sort of supplement that they had just slapped a GLP-1.

00:00:16 Stephen Carek

It was really like magnesium, some B vitamins, but the patient thought that this was some sort of GLP medication that they were receiving was helping with their diabetes.

00:00:25 Jennifer Trujillo

I think one of the jokes that I have with a lot of the people that I see in my clinic is that isn't it so great then that we get to see each other every three to six months.

00:00:36 Jennifer Trujillo

We don't have to make a decision that lasts the rest of your life today.

00:00:42 Jennifer Trujillo

You know, I'm going to see you again in three to six months and we can always reassess.

00:00:47 Jennifer Trujillo

We're not making any lifelong decisions at this moment.

00:00:55 Narrator

Welcome to Medication Talk, an official podcast of TRC Healthcare, home of Pharmacist's Letter, Prescriber Insights, and the most trusted clinical resources.

00:01:04 Narrator

On this episode, listen in as our expert panel tackles real-world questions about GLP-1 agonists, from starting them and setting expectations with patients to strategies for switching agents.

00:01:17 Narrator

You'll also hear them review key considerations to limit muscle loss with GLP-1 agonist use and discuss why some patients hit a plateau or don't respond to GLP-1 agonists.

00:01:28 Narrator

Our guests today are Dr. Jennifer Clements, a clinical professor and director of pharmacy education at the University of South Carolina College of Pharmacy, School of Medicine, Greenville.

00:01:39 Narrator

She specializes in ambulatory care, diabetes management, obesity, and endocrinology.

00:01:46 Narrator

and Dr. Jen Trujillo, a professor and the Associate Dean for Education at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences.

00:01:57 Narrator

She practices as a clinical pharmacist and certified diabetes care and education specialist at the University of Colorado Health Diabetes and Endocrinology Clinic, where she specializes in diabetes pharmacotherapy and advanced diabetes management.

00:02:13 Narrator

You'll also hear practical advice from panelists on TRC's editorial advisory board, Dr. Stephen Carek from the USC School of Medicine, Greenville, and Dr. Craig Williams from the Oregon Health and Science University.

00:02:26 Narrator

This podcast is an excerpt from one of TRC's monthly live CE webinars.

00:02:30 Narrator

Each month, experts and frontline providers discuss and debate challenges in practice, evidence-based practice recommendations, and other topics relevant to our subscribers.

00:02:41 CE Narrator

And now, the CE information.

00:02:45 Narrator

This podcast offers continuing education credit for pharmacists, pharmacy technicians, physicians, and nurses.

00:02:52 Narrator

Please log in to your pharmacist letter, pharmacy technician's letter, or Prescriber Insights account, and look for the title of this podcast in the list of available CE courses.

00:03:02 Narrator

For the purposes of disclosure, Dr. Clements reports a relevant financial relationship by serving on Speaker's Bureau for Novo Nordisk and Eli Lilly.

00:03:11 Narrator

The other speakers you'll hear have nothing to disclose.

00:03:14 Narrator

All relevant financial relationships have been mitigated.

00:03:19 Narrator

Now, let's join TRC editor and clinical pharmacist, Dr. Sara Klockars, and start our discussion.

00:03:27 Sara Klockars

So to start us off, Jen, can you give us a brief overview of how you help patients address some of these challenges when starting a GLP-1 receptor agonist?

00:03:39 Jennifer Trujillo

Well, I think for me, I try to think about 3 big ticket items when I'm starting someone off.

00:03:46 Jennifer Trujillo

The first is setting clear expectations.

00:03:51 Jennifer Trujillo

The second is starting low and going slow.

00:03:54 Jennifer Trujillo

And the third is really normalizing the experience.

00:03:59 Jennifer Trujillo

So when I'm thinking about setting expectations, I want to be clear with them about what I expect they will see in terms of benefits and side effects.

00:04:09 Jennifer Trujillo

I try to explain why we titrate the dose over time.

00:04:13 Jennifer Trujillo

And I try to talk through kind of what's normal to expect versus what's not normal.

00:04:18 Jennifer Trujillo

So, you know, if you feel a little full or mildly nauseated, that's really telling you that the medication's working.

00:04:24 Jennifer Trujillo

But if you're vomiting repeatedly and can't keep fluids down, that's not okay.

00:04:29 Jennifer Trujillo

And I need to know about that.

00:04:31 Jennifer Trujillo

And then in terms of starting low and going slow, just really explaining the why behind that, emphasizing the basics of administration.

00:04:40 Jennifer Trujillo

So eating smaller meals, eating more slowly, stopping eating when you feel full, making sure you're staying well hydrated.

00:04:49 Jennifer Trujillo

And telling patients, you likely won't eat the same way when you're on a GLP-1 as you did before.

00:04:56 Jennifer Trujillo

And then I think having a touchpoint one to two weeks after they start is just a good way to make sure that they are off and running.

00:05:05 Jennifer Trujillo

And then that last point about normalizing the experience, I try to normalize that titration phase, like, week one or two, that's really just an adjustment.

00:05:16 Jennifer Trujillo

And you're probably going to see things like appetite changes before you actually see the weight changes.

00:05:23 Jennifer Trujillo

And everyone needs a different dose.

00:05:25 Jennifer Trujillo

So your neighbor might be on one dose and you might be on a different dose.

00:05:29 Jennifer Trujillo

And we just want to find out what's going to work best for you.

00:05:35 Sara Klockars

And I think another barrier that folks run into is how do we get these covered.

00:05:40 Sara Klockars

But Stephen, I was hoping you could chime in on any tips you have for helping your patients with the cost and coverage of these medications.

00:05:53 Stephen Carek

Oh gosh, I wish there was a simple answer.

00:05:55 Stephen Carek

I always lean on my outpatient pharmacist embedded at our clinic to help with that.

00:05:59 Stephen Carek

There's some tools that are in place.

00:06:00 Stephen Carek

I think one is sometimes trying to connect patients with manufacturer cost and whatever programs may be available, but I know that for some there may be certain income barriers or paperwork that may limit that.

00:06:12 Stephen Carek

Second is we were fortunate that we have a pharmacy adjacent to our clinic that's able to offer some of these medications that through 340B pricing, so some reduced costs.

00:06:23 Stephen Carek

And then I think thirdly too, within our EMR, as long as the patient's insurance is up to date, that will occasionally be able to provide some information on insurance coverage.

00:06:33 Stephen Carek

I mean to say all that too, in the sense of a lot of these medications for the sense of bariatric purposes, I think that's providing the most barriers.

00:06:40 Stephen Carek

to getting these medicines affordable for patients.

00:06:42 Stephen Carek

But because of the expanding indications, not just diabetes, but for patients with high cardiovascular disease risk, for maybe they have hepatic steatosis, maybe they have sleep apnea, the number of diagnoses that we can now attach with a prescription for a GLP-1 is expanding.

00:06:57 Stephen Carek

And I think that is probably the biggest thing that's led to ease of affordability because now we're seeing more insurances covering these medications for reasons outside of just bariatric purposes and diabetes.

00:07:09 Craig Williams

Also, a brief is there that, as far as cost and coverage, we are reminding our medical residents on the hospital side and the clinic side to make sure you ask patients about if they're getting them somewhere else.

00:07:19 Craig Williams

We occasionally have patients who are getting them outside of the traditional health care system and acquiring them on their own.

00:07:25 Craig Williams

Ask about them along with other over-the-counter things and things that may not be in our system.

00:07:31 Stephen Carek

Yeah, that's a really good point, Craig.

00:07:32 Stephen Carek

I forgot to bring that up in the sense of just all these other third parties that are distributing these.

00:07:35 Stephen Carek

And even I had a patient that came in with a bottle that said GLP-1 on it in big letters.

00:07:42 Stephen Carek

What it was some sort of supplement that they had just slapped a GLP-1.

00:07:45 Stephen Carek

It was really like magnesium, some B vitamins.

00:07:48 Stephen Carek

But the patient thought that this was some sort of GLP medication they were receiving was helping with their diabetes.

00:07:53 Stephen Carek

So definitely it's a lot of things being out there that are just have a GLP-1 label on it that are definitely not the medication, but may influencing some decisions made since we're making in terms of supplements and just other things that they're trying to take.

00:08:06 Sara Klockars

Great points. Thank you. And I think the boxed warning around thyroid cancer has scared some folks.

00:08:13 Sara Klockars

And so, Jen, I was hoping you could comment on the risk of thyroid cancer and how you talk to your patients about it.

00:08:21 Jennifer Trujillo

The boxed warning for the GLP-1 RAs comes from rodent studies, really where dose-dependent C-cell tumors were observed.

00:08:30 Jennifer Trujillo

I think that context is really important here because rodent thyroid C-cells are different than human C-cells, and humans, we just haven't seen that clear causal signal for medullary thyroid carcinoma.

00:08:46 Jennifer Trujillo

So I think that the black box warning is really out of an abundance of caution.

00:08:52 Jennifer Trujillo

So you've got contraindication with a personal or family history of medullary thyroid carcinoma or patients that have multiple endocrine neoplasia type 2.

00:09:04 Jennifer Trujillo

Medullary thyroid carcinoma is the most rare form of thyroid cancer.

00:09:09 Jennifer Trujillo

And again, this hasn't been seen in humans. It was only seen in rodents. So I just try to put that into context for folks.

00:09:18 Jennifer Trujillo

People get worried when they have hypothyroidism and they're taking levothyroxine.

00:09:23 Jennifer Trujillo

That makes them worry, can I still take a GLP-1 RA?

00:09:26 Jennifer Trujillo

Yes, absolutely.

00:09:27 Jennifer Trujillo

So really, I think putting it into context is what I try to do.

00:09:32 Sara Klockars

Excellent. We've had some reports of patients presenting to the ED with extreme anxiety or mood changes after starting a GLP-1.

00:09:44 Sara Klockars

Jennifer, have you seen this in your practice or do you have any comments on that?

00:09:51 Jennifer Clements

I haven't seen anybody go to the ER maybe with a possible panic attack and be associated with their GLP-1 therapy.

00:10:00 Jennifer Clements

I will say that, of course, this is a warning, a precaution about changes in their mood, the risk of maybe suicidal ideation or behavior.

00:10:12 Jennifer Clements

The evidence is mixed, but it's evolving.

00:10:15 Jennifer Clements

There's even been recent news reports that perhaps the FDA will remove this from the package insert and the labels for the medications.

00:10:25 Jennifer Clements

I think regardless of the population we're talking about, right, if we are treating diabetes, there's diabetes distress.

00:10:34 Jennifer Clements

If we're treating obesity, we know that we have to address stigma and bias.

00:10:42 Jennifer Clements

They may be internalizing emotions and feelings as well.

00:10:46 Jennifer Clements

So it's, I think, still important to do baseline screening.

00:10:50 Jennifer Clements

That's very important and it's key in clinical practice.

00:10:54 Jennifer Clements

But when someone comes back for their appointments and they have a history of depression, you can, you know, still follow up with questionnaires and ask about their mood, see if there's any changes.

00:11:07 Jennifer Clements

But I've actually seen probably an opposite effect that when people do lose weight, they become more active.

00:11:15 Jennifer Clements

They feel as though they can do more.

00:11:17 Jennifer Clements

And in fact, their mood improves and they start to gain those long-term benefits with the medication.

00:11:22 Jennifer Clements

And that actually enhances their quality of life and improves their mental health.

00:11:29 Jennifer Trujillo

I think my experience has been very similar to Jennifer's in what I heard from the patients that I have in my own clinical practice, I haven't seen any extreme anxiety or significant mood changes, except in the positive direction.

00:11:45 Jennifer Trujillo

I do think it's interesting, though, you know, hearing some things on the national news or in reports of subsequent consequences of significant weight loss, you know, things that you used to do with your partner going down to your neighbors and having a few beers and some pizza doesn't become as enjoyable for you as it used to be with your partner.

00:12:07 Jennifer Trujillo

So I think it might create some new challenges that may come to the service as a kind of side product of losing weight, changing your lifestyle.

00:12:18 Jennifer Trujillo

But I haven't seen any direct reports of these medications causing extreme anxiety or mood changes.

00:12:26 Craig Williams

Yeah, I'll add, Sara, that as far as being concerned that the drug itself has like neurologic causes or toxicities, I also have not appreciated that.

00:12:34 Craig Williams

But I think Jen's maybe hitting on something that definitely has made the lay press.

00:12:38 Craig Williams

And we have had a couple bedside conversations with patients along those lines of just, you know, your body, for a lot of these patients, they've been overweight and obese their entire lives.

00:12:48 Craig Williams

And it's a pretty big deal to lose 80 or 100 pounds and it may have impacts on your social life outside of that.

00:12:56 Craig Williams

So I think mostly positive for the patient, but

00:12:59 Craig Williams

does affect relationships with, friends and spouse and children.

00:13:02 Craig Williams

And because I think for some of them, this is kind of part of their identity, kind of what they've weighed and for what they've weighed for much of their life.

00:13:09 Craig Williams

So while they appreciate the health benefits, I think we are seeing some of the social implications or complications of, you know, kind of not being that person they were for most of their life.

00:13:22 Sara Klockars

One question that we get very frequently is how long can patients use GLP-1 agonists?

00:13:28 Sara Klockars

Jen, would you want to comment on that, on the data we have?

00:13:33 Jennifer Trujillo

I think the GLP-1 RAs can be used chronically.

00:13:37 Jennifer Trujillo

They have been available for 20 years now.

00:13:40 Jennifer Trujillo

They are considered chronic therapy for type 2 diabetes.

00:13:44 Jennifer Trujillo

And like other cardiometabolic conditions or medications, they are intended for long-term use as long as they're effective and well tolerated.

00:13:54 Jennifer Trujillo

I think their utilization for weight loss is much newer.

00:13:57 Jennifer Trujillo

We don't have all the answers about the most optimal duration of therapy.

00:14:01 Jennifer Trujillo

I think many consider them the same way as chronic therapy for a chronic disease.

00:14:06 Jennifer Trujillo

And if the medication is stopped, we know that weight regain is common.

00:14:12 Jennifer Trujillo

So for many patients, this is not a short-term intervention.

00:14:15 Jennifer Trujillo

With that said, many studies really indicate that about 50% of people stop taking a GLP-1 RA.

00:14:23 Jennifer Trujillo

within the first year of treatment.

00:14:25 Jennifer Trujillo

So while I consider them to be chronic medications, we're not seeing that pan out in real life.

00:14:32 Jennifer Trujillo

We're seeing people not want to stick with them for the long haul.

00:14:36 Jennifer Trujillo

So I think it's a really important question, but I think from what we know, we can use them long-term, specifically, definitely for type 2 diabetes, and I think we can for obesity and overweight as well.

00:14:50 Craig Williams

To Jen's point, so it depends on what you're on it for.

00:14:53 Craig Williams

And for some of the non-diabetes indications, it needs to be long-term if you want to get the benefits.

00:14:59 Craig Williams

But for weight loss, where we're seeing a lot of people use it, then yeah, if we can get to a certain weight goal, let's try at least a lower dose or try coming off it.

00:15:07 Craig Williams

So we've probably all had some experience with patients who can successfully come off of them and at least not regain all the weight, maybe maintain at some level they want to.

00:15:18 Jennifer Trujillo

I'll just add to that.

00:15:20 Jennifer Trujillo

I think one of the jokes that I have with a lot of the people that I see in my clinic is that, isn't it so great then that we get to see each other every three to six months?

00:15:30 Jennifer Trujillo

We don't have to make a decision that lasts the rest of your life today.

00:15:36 Jennifer Trujillo

You know, I'm going to see you again in three to six months and we can always reassess.

00:15:41 Jennifer Trujillo

We're not making any lifelong decisions at this moment.

00:15:46 Jennifer Trujillo

And I just think that shared decision-making and that collaboration

00:15:50 Jennifer Trujillo

over time really makes a big difference.

00:15:54 Craig Williams

Yeah, and I was going to add briefly that when patients do lose a lot of weight, they feel so much better that we have had a couple patients who are the motivation kind of changes to keep the weight off when they get it off, maybe as opposed to trying to lose it kind of in the 1st place.

00:16:10 Craig Williams

So we have had some patients be able to come off it and maintain pretty close to the weight they want because they're just feel so much better at that weight.

00:16:19 Sara Klockars

One question that's come up regarding side effects and also efficacy is, are there times where you ever adjust the dose or the interval between the doses to help with that, even though they're not studied like that?

00:16:32 Jennifer Trujillo

I don't proactively suggest extending the interval, but I do definitely support and collaborate with my patients that take that approach themselves.

00:16:44 Jennifer Trujillo

So I just want to be part of the decision-making process and I want them to feel like they can collaborate with me and be honest with me.

00:16:52 Jennifer Trujillo

So I have a few patients on tirzepatide that have extended the interval and have found kind of a sweet spot for them, something that works for them.

00:17:03 Jennifer Trujillo

And they'll tell me like, you know, 10 days is the right spot for me where I still see that my glucose is well controlled, but

00:17:10 Jennifer Trujillo

I get some side effects more intensely the first day or two after I take it, and that 10-day mark just seems to be a very reasonable middle ground that works for me.

00:17:21 Jennifer Trujillo

I have a couple of patients who, for semaglutide, they do kind of half a dose twice a week instead of the full dose once a week.

00:17:29 Jennifer Trujillo

And again, I don't ever proactively suggest that, but I try to work with my patients that have found strategies that work for them.

00:17:39 Craig Williams

I would only add to that, Sarah, that I mean, if the indication is diabetes control or weight loss, yeah, they're, I mean, maybe a bit more open to if patients say this works for me at this dose and I feel better and either they're maintaining glycemic control or they have the weight loss they want, you know, I've done enough digging through FDA approvals and reviews to know that, you know, the doses and durations that companies release drugs at doesn't mean that's the only dose that works for everybody.

00:18:06 Craig Williams

We definitely stick on label when prescribing, but if the patient finds something that works for them and it's meeting the goals of their disease, I think that's a perfectly reasonable approach to take with that patient.

00:18:18 Sara Klockars

Excellent.

00:18:19 Sara Klockars

That's a great segue to digging into some GLP agonist questions for patients with type 2 diabetes specifically.

00:18:28 Sara Klockars

We're seeing them more often as we continue to individualize initial med choices, you know, considering those relevant comorbidities.

00:18:36 Sara Klockars

And so, Jennifer, can a patient on insulin also use a GLP-1 agonist?

00:18:43 Jennifer Clements

I can make this very simple and yes, they can.

00:18:48 Jennifer Clements

that is supported by the guidelines.

00:18:50 Jennifer Clements

You can look at the most recent 2026 American Diabetes Association standards of care.

00:18:57 Jennifer Clements

They have a nice algorithm in section 9 where they talk about all the medications for type 1 and type 2, but this particular algorithm towards the back of that section really reference how to use them for type 2 diabetes.

00:19:12 Jennifer Clements

And so GLP-1s are preferred injectable.

00:19:17 Jennifer Clements

There are times where insulin is initiated based on their A1Cs, being symptomatic, unexplained weight loss.

00:19:26 Jennifer Clements

But yes, they can be used together.

00:19:29 Jennifer Clements

We know

00:19:30 Jennifer Clements

that once the GLP-1 is added or the insulin is added, which way the combination is kind of starting and going, the risk of hypoglycemia goes up.

00:19:40 Jennifer Clements

But by adding the GLP-1 RA on top of that, you're able to lower the dose of the insulin.

00:19:49 Jennifer Clements

And often, you know, that's about a 20% decrease.

00:19:53 Jennifer Clements

That's what I've done.

00:19:54 Jennifer Clements

decrease initially to prevent hypoglycemia.

00:19:58 Jennifer Clements

It's a time to review prevention and treatment of hypoglycemia, to educate on monitoring, perhaps give them a CGM if they already don't have one.

00:20:08 Jennifer Clements

But there is evidence that yes, we use them together.

00:20:11 Jennifer Clements

I will say though,

00:20:13 Jennifer Clements

We're using them because we know the benefits with GLP-1 receptor agonists.

00:20:18 Jennifer Clements

In addition to weight loss, in addition to A1C, but there's still other benefits we're wanting the individual to gain, such as the cardiorenal benefits.

00:20:30 Sara Klockars

Excellent.

00:20:31 Sara Klockars

So we know patients are often on multiple diabetes meds to get their goal A1C, and we've already talked about, you know, using a GLP-1 agonist with insulin.

00:20:41 Sara Klockars

So Jen,

00:20:42 Sara Klockars

What factors guide your decision to either maintain, reduce, or stop a certain drug once a patient reaches their A1C goal?

00:20:51 Jennifer Trujillo

I feel like I go back to what I teach my students, which is who are evaluating 4 things, efficacy, tolerability, ease of use, slash treatment burden, and cost.

00:21:03 Jennifer Trujillo

And I think about how the better control you have early on in the disease of diabetes, the longer you're able to maintain.

00:21:11 Jennifer Trujillo

that great glucose control.

00:21:13 Jennifer Trujillo

So for medications that have a low risk of hypoglycemia and are reasonably well tolerated, I'm going to celebrate that great control and not want to discontinue it.

00:21:24 Jennifer Trujillo

If I'm using medications that have a higher treatment burden, heavier cost, or have side effects that I'm really trying to avoid, like weight gain or hypoglycemia, those are really going to be the first ones to go.

00:21:37 Jennifer Trujillo

And a lot of times, I think these days, we're trying to make

00:21:41 Jennifer Trujillo

room for the agents that also have added benefits beyond glucose control.

00:21:46 Jennifer Trujillo

So the GLP-1 RAs, the SGLT2 inhibitors, sometimes we're making room for those.

00:21:52 Jennifer Trujillo

And what a beautiful thing, a potential excuse to get somebody off of a sulfonylurea, which causes hypoglycemia and weight gain and just isn't all that effective and puts a lot of burden on the pancreas to make insulin.

00:22:08 Jennifer Trujillo

Sulfonylureas are going to be the first ones that I want to try to discontinue, followed by rapid-acting insulin if they happen to be on that.

00:22:18 Jennifer Trujillo

And then, you know, trying to reduce the basal insulin over time and hopefully being able to get somebody off of insulin is a real win for me.

00:22:26 Jennifer Trujillo

And then keeping patients on the medications that have benefit beyond glucose control.

00:22:34 Jennifer Trujillo

Those are really the approaches that I'm trying to take when I'm adjusting those diabetes meds.

00:22:41 Craig Williams

One thing I'll add is I wonder if you're, you know, unlike using, you know, ACEs and ARBs for hypertension or the other diabetes medicines for the most part that preceded this, most of those medications, you're on them chronically to manage your chronic disease.

00:22:55 Craig Williams

They don't, they don't fix.

00:22:57 Craig Williams

I mean, metformin doesn't, you know, fix the diabetes.

00:23:00 Craig Williams

The interesting thing here, since obesity and the

00:23:03 Craig Williams

lack of activity that often comes with that is the cause of diabetes.

00:23:07 Craig Williams

We are dealing more with what happens when a patient loses 80 or 100 pounds and their A1C is truly normalized and they're still on these medications that don't cause hypoglycemia.

00:23:16 Craig Williams

So maybe you don't have to stop them to avoid adverse effects, but do you really still need these medications when you've lost that weight and your A1C is, you know, 6 or 5.8?

00:23:27 Craig Williams

And we have had some of those conversations.

00:23:29 Craig Williams

And then

00:23:30 Craig Williams

what becomes appropriate in that setting.

00:23:32 Craig Williams

As I say, I'm always someone who loves when a prescriber or a patient says I'm on more medications than I want to be on, what can I come off of?

00:23:38 Jennifer Trujillo

It's an interesting debate between the definition of disease remission versus the definition of disease controlled.

00:23:50 Jennifer Trujillo

If somebody's on 3 meds and has a great A1C, that doesn't mean that they

00:23:54 Jennifer Trujillo

don't need those meds anymore.

00:23:56 Jennifer Trujillo

Certainly a trial of less meds, you know, is appropriate in some cases.

00:24:02 Jennifer Trujillo

What I see though, that I worry about in clinical practice is some folks that are seeing a person get to an A1C of 6.9 and wanting to stop metformin.

00:24:13 Jennifer Trujillo

And you know, there is still evidence that a lower A1C still has an impact on microvascular complications.

00:24:20 Jennifer Trujillo

So an A1C of 6.9 doesn't tell me or doesn't signal to me that I should stop the medication that is helping or is contributing to that A1C.

00:24:30 Jennifer Trujillo

But to Craig's point, when you get down in the fives, it's of course going to be a topic of conversation.

00:24:38 Sara Klockars

Thank you.

00:24:39 Sara Klockars

Jen, have you seen tolerance or a plateau effect to a GLP-1 agonist after a few years of use?

00:24:46 Sara Klockars

And if so, how should we manage this?

00:24:49 Sara Klockars

What do you do in your practice?

00:24:54 Jennifer Trujillo

I mean, in clinical practice, yes, I feel like we talk about plateau effects.

00:25:00 Jennifer Trujillo

I think people, some of my patients will say, you know, my ex-GLP-1 agonist was working great for a while, and now I feel like it's not working anymore.

00:25:11 Jennifer Trujillo

I don't really think it's a true pharmacologic tolerance, but maybe perhaps it's

00:25:18 Jennifer Trujillo

more of a physiologic adaptation.

00:25:21 Jennifer Trujillo

I don't know, like you see, I mean, we do know for weight loss, most weight loss with these men's occurs in the first 12 or 18 months.

00:25:30 Jennifer Trujillo

And then the body maybe reaches a new metabolic, you know, steady state and that's expected.

00:25:36 Jennifer Trujillo

I guess I wouldn't call that a true tolerance.

00:25:40 Jennifer Trujillo

But maybe there's just some plateaus because energy expenditure adapts or maybe appetite signaling recalibrates.

00:25:50 Jennifer Trujillo

Maybe there are more missed doses.

00:25:52 Jennifer Trujillo

Maybe caloric intake has crept up.

00:25:56 Jennifer Trujillo

Maybe they're not on the most appropriate maxed out dose that they should be on.

00:26:04 Jennifer Trujillo

I don't feel like I have a great answer because I do feel like we talk about it in clinical practice, but I'm not completely convinced that it's due to something like GLP-1 receptor downregulation or something like that.

00:26:18 Sara Klockars

So after addressing all of those, you know, different situations, addressing diet, addressing maximum doses, do you switch folks to a different GLP-1 agonist to see if they get any further benefit?

00:26:32 Jennifer Trujillo

I sure have.

00:26:33 Jennifer Trujillo

I mean, I think that there are some differences just in efficacy and tolerability between the products as well.

00:26:39 Jennifer Trujillo

So, if we're able to use a different GLP-1 that can still get covered and still get prior authorization, yeah, absolutely.

00:26:49 Jennifer Trujillo

I'll switch.

00:26:51 Sara Klockars

Thank you.

00:26:52 Sara Klockars

And why do some patients not lose weight with GLP-1 agonists?

00:26:59 Jennifer Clements

Yeah, that's a great question.

00:27:00 Jennifer Clements

And I know for those individuals, it's probably frustrating because they may have friends that have taken these medications.

00:27:08 Jennifer Clements

They've seen advertisements.

00:27:10 Jennifer Clements

They hear about them, obviously, and they take them and they don't have a response.

00:27:15 Jennifer Clements

I think it varies.

00:27:18 Jennifer Clements

What I've seen is non-responders could be anywhere from 10 to 30%, but there's probably a lot of different reasons that go into that genetic variability.

00:27:28 Jennifer Clements

Maybe there's suboptimal adherence or even titration as we previously talked about.

00:27:35 Jennifer Clements

Maybe they're on other meds that haven't been evaluated that's counteracting their progress with their weight and maybe some comorbid conditions that have been undiagnosed.

00:27:46 Jennifer Clements

Again, I think there's many different factors that go into it.

00:27:51 Jennifer Clements

Perhaps the best way to optimize support and give them guidance is

00:27:57 Jennifer Clements

maybe a referral to a dietitian, work on behavioral therapy, reassess the dose as we previously discussed.

00:28:04 Jennifer Clements

And again, with that last question, switching, maybe it's time to consider a switch.

00:28:10 Jennifer Clements

I think bottom line, there's many factors into why they may not lose weight.

00:28:16 Sara Klockars

Thank you.

00:28:17 Sara Klockars

And along those lines, what's the evidence on, you know, muscle loss for patients using a GLP-1RA and strategies to limit that loss?

00:28:29 Jennifer Trujillo

I think this question is a little more complicated than it seems.

00:28:32 Jennifer Trujillo

So first, I think when we say, sarcopenia, that's a loss of muscle mass, but also a loss of muscle strength and function.

00:28:43 Jennifer Trujillo

And, you know, I'm not an expert in this, but the study

00:28:48 Jennifer Trujillo

that look at this measure lean mass, which includes not only muscle, but bones and organs and water.

00:28:54 Jennifer Trujillo

And so that doesn't capture sarcopenia in its entirety because it's not able to really look at strength and function.

00:29:02 Jennifer Trujillo

And then I think on top of that, we see a lot of heterogeneity in the reported reductions in lean body mass from GLP-1 RAs in clinical trials.

00:29:16 Jennifer Trujillo

Systematic reviews of GLP-1REs in humans show that lean mass contributes to maybe 20 to 50% of total weight loss.

00:29:26 Jennifer Trujillo

And when you think about losing weight solely just through calorie deficit without exercise,

00:29:33 Jennifer Trujillo

they quote about 20 to 30% of total weight lost is through lean body mass.

00:29:39 Jennifer Trujillo

So 20 to 50% with GLP-1 RAs, 20 to 30% if you're talking about calorie deficit diet without exercise.

00:29:50 Jennifer Trujillo

So to me, that seems like fairly similar.

00:29:53 Jennifer Trujillo

So if you are going to lose weight at all in any way, some of that's going to be muscle.

00:30:01 Jennifer Trujillo

I don't think that the, all of the evidence is out yet.

00:30:05 Jennifer Trujillo

So more to come on that.

00:30:06 Jennifer Trujillo

I think people are looking at this pretty closely.

00:30:09 Jennifer Trujillo

But with what we know right now, what I talk to my patients about is just that it becomes incredibly important to exercise and do some strength-based exercising.

00:30:22 Jennifer Trujillo

that it's really important to eat nutrient-dense foods.

00:30:26 Jennifer Trujillo

So if your calorie intake is going to go down, you got to make sure that the calories that you're taking in are really nutritious and that you're getting enough protein in your diet.

00:30:36 Jennifer Trujillo

Those are the two things that I try to focus on and just trying to kind of bring home that message to patients that any type of weight loss, you're losing all the parts, muscle and fat.

00:30:49 Sara Klockars

Stephen, do you have anything else to add?

00:30:53 Stephen Carek

No, I sort of counsel the patients in a similar fashion.

00:30:56 Stephen Carek

I used to tell patients these medications, you're going to lose weight anywhere and everywhere that you can.

00:31:14 Stephen Carek

But oftentimes we forget to emphasize the strength training and resistance training component of this.

00:31:19 Stephen Carek

and try to make sure people are getting two days a week of resistance activities, whether it's body weight resistance band up to weightlifting.

00:32:38 Sara Klockars

Thank you, Stephen.

00:32:39 Sara Klockars

So I do want to just quickly address switching because we've had a lot of questions about that.

00:32:46 Sara Klockars

How do you switch?

00:32:48 Sara Klockars

Do you need to start the new one at the starting dose?

00:32:50 Sara Klockars

Can you convert?

00:32:52 Sara Klockars

Craig, Jennifer, have you run into this and can you kind of guide us through the process?

00:32:59 Craig Williams

Our general approach is you can, you know, make a table of kind of typical dosing and kind of compare, but I don't have a good, like,

00:33:07 Craig Williams

one-to-one milligram per milligram conversion between them, so they don't have like an opioid conversion table equivalent for GLP-1s.

00:33:15 Craig Williams

I will say, though, if someone's been doing well on what is kind of a medium or high dose of injectable GLP-1 and they need to switch for insurance reasons, we do not go back and start

00:33:25 Craig Williams

at the beginning and re-titrate up.

00:33:27 Craig Williams

We'd become pretty comfortable starting at what seems like kind of a comparable dose for that agent, and that generally seems to have gone pretty well.

00:33:35 Craig Williams

But I've had not much experience moving back and forth between the orals and the injectables, but that's been our approach for different injectables.

00:33:43 Jennifer Clements

I haven't switched from orals to injectables.

00:33:47 Jennifer Clements

It's always been more of a conversation of how comfortable we feel with injectable to injectable.

00:33:55 Jennifer Clements

where are they currently with the dose on their injectable now versus where do we feel comfortable going on a new agent?

00:34:04 Jennifer Clements

But I do think it's a good conversation because pretty soon we're probably going to have another oral product on the market based on what I know about it.

00:34:16 Jennifer Clements

And so some of its evidence has been looked at following

00:34:23 Jennifer Clements

a course of injectable therapy so that it can help maintain weight loss, knowing that maybe some people don't want to inject long-term and that switching them then to an oral agent would be the best option.

00:34:39 Jennifer Clements

I do think that is coming, but always the conversation has been more of switching injectables to another one.

00:34:48 Jennifer Clements

Do we have to go back to the beginning or do we feel comfortable

00:34:52 Jennifer Clements

if they're on semaglutide 2.4 milligrams, then I can start tirzepatide 5 and skip the starter dose.

00:35:00 Sara Klockars

And then if you have a patient off of a GLP-1 for quite some time, do you always restart them?

00:35:10 Sara Klockars

Or if they were tolerating, say, a higher dose and then they missed it for a couple of months, would you just jump back into that higher dose?

00:35:17 Sara Klockars

What have you done in practice, Jennifer?

00:35:21 Jennifer Clements

Yeah, I mean, there's times I'm not going to lie that we start right back from the beginning because perhaps they were an individual that tended to have a little bit more nausea, vomiting for every time the dose was previously escalated.

00:35:34 Jennifer Clements

However, I always say how long have they been off of it?

00:35:37 Jennifer Clements

I think that comes up when people have planned procedures.

00:35:41 Jennifer Clements

Sometimes they get told that they have to go back to the beginning because they held it for a week or, you know, in case that got extended a little bit, you know, into week two or something.

00:35:51 Jennifer Clements

But if they were fine before, you could, in my opinion, restart.

00:35:56 Jennifer Clements

They were on a really high dose and have been off of it.

00:36:00 Jennifer Clements

I think that's obviously a conversation with the patient.

00:36:04 Jennifer Clements

Do they feel comfortable?

00:36:05 Jennifer Clements

Do they understand what may happen?

00:36:08 Jennifer Clements

I wouldn't recommend starting, you know, tirzepatide 15.

00:36:12 Jennifer Clements

If that's where they left off six months ago, maybe I would feel comfortable with five.

00:36:18 Jennifer Clements

If they are like, just start me at the beginning, that's great.

00:36:21 Jennifer Clements

But I do know that sometimes insurance companies may limit you, particularly when we're looking at obesity with some of those doses that you're using to get to the next maintenance dose.

00:36:36 Jennifer Clements

And so what I mean is that insurances may limit you to just one month.

00:36:40 Jennifer Clements

So that's a conversation

00:36:42 Jennifer Clements

that you also need to have with the patient and check to see if there are going to be those limitations tied to it.

00:36:50 Craig Williams

Yes, that's a good point.

00:36:51 Craig Williams

It may not be our choice in terms of whoever's paying for it definitely might have some say in that.

00:36:55 Craig Williams

I think context matters.

00:36:56 Craig Williams

If the question is, you know, if you're switching between agents because insurance changed or something got dropped, then yeah, we're comfortable kind of going to what seems like a comparable dose.

00:37:05 Craig Williams

But to our earlier discussion, if you're changing because someone wasn't tolerating the one you're using, then we will generally start at the

00:37:11 Craig Williams

lower dose because higher doses definitely have more adverse effects for most patients.

00:37:15 Craig Williams

And so we want to set that patient up to succeed if we're changing because they were intolerant of it and we'll always start at the beginning.

00:37:22 Craig Williams

And I think if they've been off it for a long time, I mean, generally lower doses are better tolerated.

00:37:27 Craig Williams

So we are generally starting at the starting dose if they've been off it for a long time and we're reinitiating in that patient no matter what their experience was with it previously.

00:37:39 Narrator

We hope you enjoyed and gained practical insights from listening to this discussion.

00:37:43 Narrator

Now that you've listened, pharmacists, pharmacy technicians, physicians, and nurses can receive CE credit.

00:37:49 Narrator

Just log into your pharmacist letter, pharmacy technician's letter, or Prescriber Insights account, and look for the title of this podcast in the list of available CE courses.

00:37:59 Narrator

On those websites, you'll also be able to access and print out additional materials on this topic, like charts and other quick reference tools.

00:38:06 Narrator

If you're not yet a pharmacist letter, pharmacy technician's letter, or prescriber insight subscriber, now's the time.

00:38:13 Narrator

Sign up today to stay ahead with trusted, unbiased insights and continuing education.

00:38:18 Narrator

And as a listener, you can save 10% on a new or upgraded subscription with code MT1026 at checkout.

00:38:28 Narrator

Be sure to follow or subscribe, rate, and review this show in your favorite podcast app.

00:38:33 Narrator

or find the show on YouTube by searching for TRC Healthcare or clicking the link in the show notes.

00:38:39 Narrator

You can also reach out to provide feedback or make suggestions by emailing us at contactus at trchealthcare.com.

00:38:49 Narrator

Thanks for listening to Medication Talk.