Meds for Obesity and Weight Loss

Special guest Jennifer N. Clements, PharmD, FCCP, FADCES, BCPS, CDCES, BCACP, BC-ADM,  Clinical Professor and Director of Pharmacy Education from the University of South Carolina College of Pharmacy joins us to talk about meds for obesity and weight loss.

Listen in as they discuss management of overweight and obesity, including the role of newer injectable medications, oral options, and lifestyle changes.

You’ll also hear practical advice from panelists on TRC’s Editorial Advisory Board:

• Stephen Carek, MD, CAQSM, DipABLM, Clinical Assistant Professor of Family Medicine, Prisma Health/USC-SOMG Family Medicine Residency Program at the USC School of Medicine Greenville
• Andrea Darby Stewart, MD, Associate Director, Honor Health Family Medicine Residency Program and Clinical Professor of Family, Community & Occupational Medicine at the University of Arizona College of Medicine - Phoenix
• Craig D. Williams, PharmD, FNLA, BCPS, Clinical Professor of Pharmacy Practice at the Oregon Health and Science University

For the purposes of disclosure, Dr. Clements reports relevant financial relationships [GLP-1 agonists] with Eli Lilly, Novo Nordisk (speakers bureau).

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

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The clinical resources mentioned during the podcast are part of a subscription to Pharmacist’s Letter and Prescriber Insights: 

• Chart: Weight Loss Products
• Toolbox: Weight Loss: Helping Your Overweight and Obese Patients

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Transcript

This transcript was automatically generated.

[Intro Music]

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

On today’s episode, we’ll listen in as our expert panel discusses management of overweight and obesity, including the role of newer injectable medications, oral options, and lifestyle changes. 

Our guest today is Dr. Jennifer Clements from the University of South Carolina College of Pharmacy. 

You’ll also hear practical advice from panelists on TRC’s Editorial Advisory Board

Dr. Stephen Carek from the USC School of Medicine Greenville

Dr. Andrea Darby Stewart from The University of Arizona College of Medicine - Phoenix

and Dr. Craig Williams from the Oregon Health and Science University.

This podcast is an extract from one of TRC’s monthly live CE webinars    . Each month, experts and frontline providers discuss and debate evidence-based practice recommendations.

The full webinar originally aired on January 23rd, 2024.

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And now, the CE Information.

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This podcast offers Continuing Education credit for pharmacists, physicians, and nurses. Please log in to your Pharmacist’s Letter or Prescriber Insights account and look for the title of this podcast in the list of available CE courses.

For the purposes of disclosure… 

Dr. Clements reports relevant financial relationships as a speakers bureau participant with Eli Lilly and Novo Nordisk.     

The other speakers you’ll hear have nothing to disclose. All relevant financial relationships have been mitigated.

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Now, let’s join TRC Editor, Dr. Jeff Langford, and start our discussion!

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JEFF LANGFORD:

And this topic I think most of us are aware that it's really taken center stage in the last several months to a year for multiple reasons. We've seen the rate of obesity climb dramatically in the US over the past few decades often leading to this being labeled a public health crisis and dubbed an obesity epidemic. But within that context we now have these newer meds for weight loss that are highly effective compared to options that we previously had. And we also have data showing that one of these meds, somaglutide, reduces cardiovascular risk in patients with obesity. And that's a bit of a contrast to some of the cardiovascular concerns that we had with agents in the past. So all of those factors kinda taken together contribute to this really being top of mind for us as clinicians and being squarely in the spotlight of lay press coverage for our patients as well. So Jennifer I want to, with all of that in mind, I want to ask you if you can just kind of help us get started by reviewing the prevalence of obesity in the US, and we'll talk a bit about how that's classified to better understand it as well. 

JENNIFER CLEMENTS:

Sure. Overall in the United states the prevalence of obesity is around forty two percent, and that is defined as a BMI or body mass index equal to and above thirty. I think what is important to note is while we know the current prevalence, it is predicted that the prevalence of obesity will go up to fifty percent by the year 2030. So I think that that, again is a little bit more of a statistic that we should keep in mind as we move forward and really apply that to clinical practice and have the conversation about weight loss and weight management with individuals in practice

JEFF LANGFORD:

You did mention that BMI greater than thirty was classified as obesity And I wonder if we can talk a little bit more about that.

JENNIFER CLEMENTS:

Once the BMI is equal to or above thirty that could be further classified. In a different way as class one, two or three. So class three would really be that severe obesity that you see at the bottom of a BMI equal to and above forty kilograms per metered square. So again this is a measurement of, you know weight over height, and so it's often used in clinical practice because it's fairly easy to do when a person is being triaged, into… in clinical practice basically, so our EMRs or electronic health records can easily calculate that and plug it in and even bold it in some people's charts. So, again it's often used in clinical practice, but I think now there's been discussion about is it the best way to measure obesity or weight?

JEFF LANGFORD:

What are some of the limitations of that and what additional measures would you really consider…practical to use in your clinic or site?

JENNIFER CLEMENTS:

Yeah so there's been a couple of things that I've used in clinical practice. I've done waist circumference before, in using that consistently among certain individuals. I've also used different devices in practice to measure maybe body fat percent…I think that's a great device as long as you use it consistently…because it could vary. Depending on again what type of device that you're using. Some people like to do the waist to hip ratio because that could also correlate…with maybe a higher risk of certain complications…and give you some more information.

JEFF LANGFORD:

Okay. Well Stephen I'd like to pull you into this and talk a little bit with the background that we've had about prevalence of obesity and kind of how to identify and classify that. Is you're engaging with patients and talking about obesity? What are some of the health risks or health concerns that you may introduce into that conversation or what help risks are top of mind for you as you're evaluating those patients?

STEPHEN CAREK:

Yeah and you mentioned early sort of uh obesity is very much sort of an epidemic or injury night right now. And why is that? It's because that it, it can potentially lead to so many conditions of early mobility and mortality that afflict our nation, and these range for things like heart disease early cardiovascular disease heart failure, stroke, diabetes, certain cancers and like breast cancer colorectal cancers, and liver disease, liver cancer, arthritis I mean it really it comes to so many potential disease states that touch on so many processes in the body that just the amount of conditions and as I salute to or getting mortality can lead to is is tremendous and it really represents sort of how this can affect the body in so many different ways across so many different organ systems.

CRAIG WILLIAMS:

I just add to that really briefly Jeff that...

JEFF LANGFORD:

Yes please.

CRAIG WILLIAMS:

Those are great comments and yeah it really is kind of an overall quality of life factor. For so many people but the the things here the one that often still catches people by surprise is a cancer…link. And I think almost we become so good at treating heart disease that maybe does scare people as much as it did before statins and blood pressure control and ten and twenty years ago but the cancer link is real. And a lot of patients aren't aware of that and that still gets people's attention and can be a definitely an extra motivator…

JEFF LANGFORD:

So Jennifer with these health concerns in our mind let's let's kinda flip that coin and talk about what are the health benefits of weight loss and how do you frame those benefits for patients in your discussions…

JENNIFER CLEMENTS:

Yeah Once I you know ask for permission to really discuss any sort of weight issue I I want the individual to feel comfortable and know that they're not going to be judged for whatever they share with me. But I do think it's very important to engage them in that conversation…so that they can share their thoughts about what they think the benefits are as well as what they see their goal being, because there are individuals that don't have realistic goals and so we need to set them up for success, and that's where we often try to promote at least a minimum of a five percent weight loss. So that we can improve those cardiometabolic…parameters…like blood pressure cholesterol and glucose…But really we know too that when they lose weight they're going to feel better, they will get around better have improvement in their quality of life. And that could even lower their risk of other complications down the road. We're seeing though that the larger and sustained weight loss is really in important. And I'm sure we'll talk about that here in a little bit particularly when we get to certain medications, but You know five percent is the minimum. You can get more so the greater the weight loss the greater the benefit in terms of what they will gain from losing weight…

JEFF LANGFORD:

And as we think about how to do that, Andrea I'd like to answer a question I think that is really top of mind especially as we consider lots of drug therapy options and and that is really is lifestyle change… foundational and and what's your perspective on that Andrea?

ANDREA DARBY-STEWART:

I almost feel like this is a little bit of a trick question. So for me the lifestyle changes that we want to ask our patients…who have obesity…are the same lifestyle…changes that I would like to see in all of my patients who don't have obesity, but may just be trying to kind of achieve their best wellness so we know that increasing even a modest amount of exercise or movement is good for almost everybody I can't, there are very few people I would say that that's not a good choice for. We know that trying to limit those highly concentrated over processed foods and focusing on things that are perhaps have more nutrition available to them are going to be more healthy for everyone And so I try and emphasize to people that what we really wanna do is not make a dramatic change. That is special and unique to them but really something that we try and optimize for all of our patients. So exercise or movement of any type that feels comfortable…managing nutrition, managing sleep, managing your emotional health and wellness are all steps that all of our patients can take on that journey toward weight loss and are in general things that I hope that we're promoting for all of our patients.

CRAIG WILLIAMS:

I think that's right Andrea, yes. But sometimes our patient's goal is to stop gaining weight You know every six months you see them and they weigh ten fifteen pounds more So my initial goal could be not gaining weight in the next year as opposed to how much you're gonna lose And so yeah starting small is really important. 

STEPHEN CAREK:

Yeah I agree with a lot of those those comments And when I counsel patients on Lifestyle specifically I think it's always decision between diet and exercise of which one and where do we start and I can't speak to the power I I the the power of weight loss is really through that calorie deficit I think and through those nutritional choices as alluded to picking foods avoiding the processed food avoiding those foods that are really calorie dense You're thinking candy bars small volume high calories. Physical activity is fantastic I think should be including a lot of these counseling interventions we have with patients. It's excellent for cardiovascular health reducing blood pressure. Weight loss it's okay I mean we have to really get into that three hundred minutes a week to really start seeing noticeable weight loss with physical activity alone, but you put physical activity and weight loss together It really is sort of the wonder drug I think Outside of these medicines we're gonna talk about later in helping patients uh achieve weight loss goals…

JEFF LANGFORD:

Well Jennifer let's turn to the next question and kind of pulling in the discussion about these medications…for management of obesity And I'd like to kind of on what is the role of these medications and and when should we consider, at least have them on the table as a consideration for management of overweight or obesity? 

JENNIFER CLEMENTS:

The first thing to keep in mind is that this is not to replace lifestyle modifications. This is in addition to lifestyle modifications and that specifically is a reduction in caloric intake as well as increased physical activity. Where it falls is you know or where people could be candidates for these particular weight loss medications is when their BMI is again, in that category of obesity so equal to above thirty or they're overweight, and so that's the BMI equal to an above twenty seven with the presence of a weight related comorbid condition so dyslipidemia, hypertension, diabetes, sleep apnea. Most often these medications have been studied in those with hypertension, dyslipidemia, as well as type two diabetes. But this is really how all of them are indicated. So in terms of their labeling and that's because that's how they were studied, in the clinical trials, and there was an old document back in 2008 that the FDA had come out and really supported the inclusion criteria for these particular medications which really drove a lot of that, but that's what they have in common across the board when we're looking at when to use them in practice…

JEFF LANGFORD:

Okay. And we do have a list here of medications select to agents that are approved for obesity and familiar choices starting with phentermine and then phentermine in combination with topiramate…or list at naltrexone and bupropion in combination…And then several injectable agents including loraglutide semaglutide and tirzepatide. But what we've seen in in recent months is the spotlight really on semaglutide and tirzepatide and and Jennifer, tell us a little bit about why that is Why why have these drugs really uh garnered so much attention…in recent months. 

JENNIFER CLEMENTS:

What's really great about the evidence behind them is you're seeing…drugs get closer and closer…to the results that are seen with bariatric surgery so It's where we're talking about those larger and sustained…weight loss goals because the studies are reporting not just the five percent…But what is the percent or proportion of people losing ten percent or more? Fifteen percent or more And even In some cases twenty percent or more of their weight from baseline…with those, you know new medications like trizepatide for instance. So they're really kind of pushing the needle closer than what we've seen before with older medications or what we could say are established medications for weight management so they're getting closer, and they're showing really good evidence. And I think that We're gonna see you know more come out because even with semaglutide as you mentioned in the beginning you know the buzz too is that we have cardiovascular evidence and that could lead to discussions with…payers picking up finally these medications…

JEFF LANGFORD:

Okay, that's a really nice summary and I like the emphasis that as you said they're kind of pushing the needle closer to that bariatric surgery…realm And I do wanna just go back briefly and touch on the numbers in our in our articles that we published on this. We included…the absolute weight loss. And what we included in our article was that using tirzepatide fifteen milligrams per week led to an average weight loss of about forty one pounds And that was compared to lifestyle change alone…a one year treatment uh comparison period. And some agletide the absolute weight loss seen in a similarly designed study was about twenty seven pounds more than lifestyle change alone over about a year So Craig I wonder with that context if you can help us kind of unpack what we've seen around CV outcome studies with semaglutide specifically in this patient population and what kind of data we might be looking…toward uh hearing about tirzepatide perhaps in the future. 

CRAIG WILLIAMS:

Yeah I mean I think a lot of us would be surprised if there was not benefit from tirzepatide but you have nicely quoted in the article The And really the landmark trial that put CV events kind of on everyone's…schedule was just published last December and Yeah This is the right quote of the endpoint and that's over about three years of the trial So to some people that I don't know what that sounds like a lot or a little but to have one primary CV event for you know less than the street of a hundred. In about three years that's pretty good And so, uh yeah as we've been saying that we're getting into some real cardiovascular benefits. I think there's questions around in a lot of our minds but my pharmacologist hat on…how much is that is tied to weight loss and how much might be other effects So there's a lot of things about these drugs There's still a bit of a black box that we're having trouble kind of unpacking exactly…what these benefits are from There's no doubt weight loss contributes for the anti inflammatory effects and other aspects we don't understand but it it looks like it's not entirely…just that So you don't necessarily have to have the weight loss to have some CV benefit There's a lot more sub analysis of the big trial to come but yeah it's a broad effect across endpoints at a rate that you might expect to see you know for statins or drugs if you used historically to lower CV end points So and then but this really is kinda fairly recent that it's kind of on our radar to this magnitude. 

JEFF LANGFORD:

Well as we think about these medications and…weight loss medications in general, what is a practical approach to choosing one of these medications…for management of obesity? 

JENNIFER CLEMENTS:

I think there's probably various ways that we all look at it and yet some similarities i mean of course we can say we're gonna look at the person in front of us and there are you know specific factors that they have like their medical history, other drugs etcetera. And we're gonna consider…each option based on how it works. The contraindications adverse events. I I tend to always think about safety first, you know, because…That's a concern because if they have adverse events you wonder will they discontinue it? Will that cause us not to titrate the doses As we should maybe get to a point for more weight loss because often it could be a dose dependent manner where you get additional weight loss. But, obviously I think too you've got to engage the individual in the conversation and talk about the cost of these medications because…that's obviously one of the barriers in practice is that we just don't have that great coverage or there's gonna be a high co pay And even as you try to use certain copay cards and get the price reduced that still could seem like a large amount of money for that individual where to someone else that may not seem that way. But I do think you should look at it as far as safety, tolerability the simplicity each of these drugs It's different in how they're dosed and their titration some are complicated…and some are a little bit easier and I think that's important to consider when you look at a drug and consider it for the person. 

JEFF LANGFORD:

Okay Well in our article uh after kind of offering guidance around tailoring the selection of all those goals and comorbidities some of the points that we just discussed. We kind of came to a bottom line recommendation a considering tirzepatide if it was practical for patients perhaps with severe obesity since it may lead to more weight loss or considering semaglutide for patients with cardiovascular disease based on CV benefit. Well let's move to kind of the next area of consideration and our article we note that despite a lot of these positive points that we've discussed it's not all smooth sailing with these medications and there are important considerations…both in terms of safety as well as routine adverse effects perhaps and and access as well And I'd like to unpack that a little bit and Stephen I'm gonna start with you to just kind of ask what are some of the adverse effects that you consider…common with these newer injectable agents and how do you approach those conversations with your patients? 

STEPHEN CAREK:

Yeah And Most common is gonna be those GI side effects that are related to these medicines namely the nausea, um that experience with initiation and dose titrations and the way I usually manage those with patients is one we start low, we start low and slow Start the lowest dose. Typically for these I usually say in try it for four weeks before we consider a dose titration And the thing with that is just to help them experience manage and and overcome some of these side effects And even counseling them too that maybe it's not just related to some of that delayed gastric emptying and early satiety that try eating smaller meals maybe more frequent meals that may help reduce some of those symptoms too. The the bigger uh long term side effects that we worry about you know there's some data merging about more biliary tree issues namely things like colysisitis biliary colic potentially even gallbladder cancers that's seen in sort of long term stuff I you know kinda rare but still something I bring patients attention to especially those patients that sort of meet those age demographics We think sort of our middle age women maybe having a higher risk for failure disease, pancreatitis being one always counseling patients on the intractable nausea bombing pain Although a very rare side effect I've seen maybe once or twice maybe a patient that may have had anchoritis triggered by a GLP one agonist.

JEFF LANGFORD:

Okay I'd like to ask Jennifer to interject here if I could around managing those GI effects were seeing an audience question come in that I imagine is pretty common in practice and that's if it's appropriate to use medications to relieve nausea and wondering what you think about that Jennifer and if you ever give symptomatic meds for on a kind of PRN basis to help mitigate some of these effects. 

JENNIFER CLEMENTS:

My approach is really we gotta do some quick education first so there's gonna be education when you start the medication to make them aware and the reason why you're starting low and you titrate we can't just bump you up to the highest dose. Because then you won't take it and…we gotta provide that education on what to expect when they get the first prescription and then definitely at the titration but I do think you can start without having to pile on other meds or think about something empirically…Just do something very quick Ask them about their portion sizes, you know and this is probably after they've been on it for a month or longer. What are your portion sizes So start there then ask what types of foods are you eating, meaning…Are you eating a lot of fatty foods greasy foods spicy foods Cause that could contribute to nausea, then ask them what they drink And encourage them to try to drink plain water, etcetera. And so I think trying that first really focusing on a quick education you could create even a quick handout to give to them as a reminder when they leave the clinic. And that way, you allow them to try that before then adding on something that may be PRN…to help alleviate those adverse events especially based on how frequently they may be occurring. But I'd…really would encourage that approach rather than just adding on more medication…just because then I feel like we get into maybe a spiral or some poly pharmacy there because we know this could happen and we know when it could happen with the titration of the drug. So it's very important to maybe try that lifestyle first. 

JEFF LANGFORD:

Okay I like that and I appreciate that we heard a nice perspective…of different different but complimentary ideas on how we can educate our patients about incorporating the appropriate lifestyle measures to start with So I think that's very helpful. 

CRAIG WILLIAMS:

There's a lot of great comments, Jeff the I mean portion controls, something you should discuss there going up front So let's just make sure patients know what might be coming And then yeah lowest slowest dose and portion control And and yeah we that gets a lot of patients through the first few weeks successfully. 

JEFF LANGFORD:

Okay Thank you Craig And while I have you on talking about some of these different considerations I do wanna touch a bit on drug interactions Another question that that we've been asked is specifically this potential interaction between tirzepatide and oral contraceptives, and I'd be interested in your thoughts on how you manage this interaction and what you might recommend…on this point. 

CRAIG WILLIAMS:

Yeah You have to be aware of it and that's we just go with the labeling so because These drugs affect gastric clearance The recommendation is if you're using oral…contraceptive, uh add a barrier method for force four weeks after starting and after a dose titration. Doesn't affect other methods obviously So if anyone's using uh you know norplant ejection type or IOD so alternative…options to be considered But yeah with the four weeks of uh alternative contraception around initiation and dose titration is a good idea and is what's in the package insert. 

JEFF LANGFORD:

I think this is a good point Andrea to turn back to an a very important underlying point And we we've alluded to it so far but I do wanna talk a little bit about cost and access of these medications and average cost for these agents without payer coverage is around twelve hundred dollars per month And I'm wondering Andrea how you navigate that in practice How does that impact access and and how do you work through that? 

ANDREA DARBY-STEWART:

Yeah You know honestly it's been quite a challenge and I've noticed a large difference at the beginning of the year Many of our payers have specifically noted that they are not going to be covering the cost of these medications as weight loss medications. So if you happen to have diabetes, you can be treated with these medications and have the benefit of weight loss. But if you don't many of my patients have found themselves…basically unable to fill the medication. And you know no matter how many coupons you get and what the lower cost is that lower cost may be too much before many of our patients because of their strain financial circumstances. I happen to have a work with a lovely ambulatory clinical pharmacist and she does her best to try and help my patients out with these medications. But it's been a little disheartening for some of my patients to have to stop the in this calendar year You know I think the other thing to talk with patients about as we initiate these is the the conversation about this being a long term medication. And the fact that for as long as they're capable and willing to this is a financial commitment…to that ongoing wellness and weight loss journey And I think sometimes that's hard for people because we have a culture that is so very much about yoyo dieting and take this quick fix and that's how many of our other weight loss management options have been for them. And so really thinking about what this means long term for them and their and their their health about their financial health as well as their overall physical and mental wellness. 

JEFF LANGFORD:

Okay. And Jennifer I want to Andrea gave us a really nice introduction to the idea that these meds to be considered for long term use And I wonder if you can unpack just briefly some of the data that we have about what happens when we stop these medications in terms of the impact on efficacy…

JENNIFER CLEMENTS:

Sure This is a common question that comes up particularly…as what was mentioned about using it long term. So really if you looked at any of the drugs that we showed earlier that are indicated for weight loss when you…stop the medication, The individual will gain weight back and they may go back to where they were at baseline or slightly below that We know that there are some individuals in practice that tend to gain weight above where they were before they started the medication so again each individual is different. But the trend is if you stop it they will gain weight back And so those studies have showed that you know once they continue on maybe from the first year with the drug they then re randomize them And so Whether they got semaglutide again for additional time or placebo…switching them and not giving them drug just leads to weight gain. 

JEFF LANGFORD:

Thank you for that Jennifer. In our article I want to touch just very quickly on this We did say that while these newer agents are in the spotlight that…often oral medications may… And I want to just quickly look at some specific examples of efficacy with those oral agents. So if we kind of rank them from top down we could see that phentermine to pyramid compared to placebo average weight loss With that combination product was around nineteen pounds. But with naltrexone bupropion fintramine or orlistat we drop below the ten pound average weight loss versus placebo. And those studies often running for about a year. So efficacy does decrease but we may need to consider them in some cases…And I wonder Jennifer if if you might be able to just talk about specific indications when we might consider one of these oral agents preferentially…if there are any kind of disease states or patient considerations where we might look to one of these perhaps as a second choice if one of these newer injectables is not an option…

JENNIFER CLEMENTS:

Sure I'll just probably hit on maybe one thing per drug because I could go on about each one but…Yeah for instance, as mentioned on here you know, if you wanna use fentering plus topiramate, you know maybe they do have a history of migraines but also both of those medications…come as generic by themselves so we know that that could lower the cost rather than using the brand name product. Again because they're both generic and that could lower the cost but there's definitely some other considerations. If someone has depression, maybe you use the bupropion plus but you do need to watch out for the contraindications…because it is a long list with that particular medication. With some of the other ones you know while you asked about oral products you know often fitterming by itself is only short term so maybe that's a way to just kind of kick start someone's weight loss journey, and then they can further work on lifestyle modifications…or go to another drug but it's only for twelve weeks. But again you have to look at cardiovascular what's their blood pressure What's their heart rate? Or list that It's So many times a day it's often very hard And with its adverse event or safety profile people often discontinue it. 

JEFF LANGFORD:

That's really a a great summary. And as we move toward the to closing things out Jennifer any any tip that you really focus on sharing with learners and trainees I know that's part of of your role as well…

JENNIFER CLEMENTS:

Yeah. I would say that my clinical pearl would be empower, educate and advocate so we wanna empower those living with a higher body weight to take, you know the appropriate steps, even if they're small steps that they can be success for long term I think educating them…about obesity, the complications…the options that are available etcetera, but then advocating for change because…as we discussed there's new evidence coming out. That I hope in…two years at least we do see the change and we're able to get these options a little bit easier…for the individuals that really can benefit because we've seen some limitations or barriers in clinical practice.

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

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