This transcript is automatically generated.
00:00:04 Narrator:
Welcome to Rumor vs Truth, your trusted source for facts, where we dissect the evidence behind risky rumors and reveal clinical truths. Today, we'll weigh the facts behind side effects claims for GLP-1 agonists.
00:00:21 Steve Small:
Well, hey, Don, your, uh, your background's looking pretty festive there.
00:00:25 Don Weinberger:
I know getting into the holiday spirit. And I guess with that, the holiday pounds. What about you, Steve?
00:00:31 Steve Small:
Yeah, I gotta, I gotta be careful with all those. All those holiday cookies. Uh, and, you know, it makes me think of New Year's resolutions as well. And before we even get into that, I'm Steve, the pharmacist.
00:00:41 Don Weinberger:
And I'm Don, the pharmacist.
00:00:43 Steve Small:
And we could talk all day about our favorite holiday foods. But in this episode, we're actually going to look at what seems to be a favorite topic in pharmacy right now GLP-1 agonists that we use for diabetes and weight loss.
00:00:55 Don Weinberger:
And we haven't lost our appetite for evidence. Specifically, we wanted to know whether newer side effect claims and headlines and in social media for GLP-1 agonists such as semaglutide or liraglutide are the real deal. I was going to pop some popcorn for this episode, Steve. Uh, maybe we were just corny enough.
00:01:15 Steve Small:
Yes, even though that would sound amazing, it does sound pretty good right now. But you know what's also good, Don? The fact that this episode now offers continuing education credit for pharmacists, pharmacy technicians, prescribers, and nurses. And plus, it's calorie free.
00:01:33 Don Weinberger:
Just log in to your pharmacist letter, pharmacy technicians letter, or Prescriber Insights account and look for the title of this podcast in the list of available CE courses.
00:01:41 Steve Small:
And for the purposes of disclosure, none of the speakers today have anything to disclose.
00:01:45 Don Weinberger:
So before we deep dive into these side effect claims, we should briefly review what these meds are and how they work.
00:01:51 Steve Small:
That's a great idea. GLP-1 stands for glucagon like peptide, a class of hormones, and there's also a related class called GIP or glucose dependent insulinotropic polypeptide. So quite the mouthful.
00:02:04 Don Weinberger:
And it rolls off the tongue, doesn't it? Whenever we use acronyms for them. But these were originally developed to treat diabetes. Since GLP-1 agonists help stimulate insulin secretion, remember we talked about lizard saliva being the source of the first marketed GLP-1 Byetta. In our retro rumor episode. So go check that out. Anyway, these GLP-1 also slow down stomach emptying which can decrease blood sugar spikes. And that's just some of their effects right there.
00:02:33 Steve Small:
Delayed stomach emptying effect can be helpful here, since it can make patients feel fuller, faster, and eat less overall. And these meds also interact with receptors in our brain involving appetite. So now you see many commercials about versions that are recently approved for weight loss, such as Wegovy for semaglutide and Zepbound for Tirzepatide.
00:02:54 Don Weinberger:
Right. And because of that, studies have found that these meds can help patients lose up to twenty percent of their weight over one year when paired with lifestyle and diet changes.
00:03:04 Steve Small:
Yeah, that's an important combo, and the use and popularity of these meds keeps booming. With more approvals in use. Naturally, we're seeing more unique side effect claims out there.
00:03:14 Don Weinberger:
Yep, you said it. And we've known for a while that these meds can cause GI side effects. Things like nausea, abdominal pain, constipation, or diarrhea.
00:03:24 Steve Small:
Yeah, those are classic. And now emerging side effect claims are adding concerns on top of this. And Don, it's already hard to keep track of all the various GLP-1 products coming out, let alone more possible side effects on top of that.
00:03:38 Don Weinberger:
Yep. So Steve, we have a handy dandy interactive GLP-1 and GIP GLP-1 receptor agonist comparison chart again rolls off the tongue to help us sort through these products. It reviews different meds in this class, along with indication, dosing and more.
00:03:54 Steve Small:
Handy indeed. And that's a really good reminder. And let's not forget another good reminder here. Be sure to stick around towards the end when we're going to answer our question about apple cider vinegar. Listener actually submitted after our last episode on natural cold and flu remedies, so check it out.
00:04:10 Steve Small:
Now, first, our first side effect claim here is on the top of many people's minds. It's that GLP-1 agonists can lead to hair loss. Now to answer this one, I enlisted the help of our fellow editor, Sarah Klockars, PharmD, BCPS, who specializes in dermatology. You might remember her from some of our past episodes. So let's hear what she had to say. Well, welcome back to the show, Sarah, and thank you for helping us out with this claim about hair loss side effects with GLP-1s. And I am curious, what is your take on this?
00:04:45 Sara Klockars:
Yeah. So there have been some reports of patients with hair loss. It's also called alopecia or hair thinning on the scalp while taking these meds. And most of these are case reports and observational studies. So they're not randomized controlled trials that deal that say GLP-1 are a cause.
00:05:05 Steve Small:
Yeah, that's a really good point there. And for our folks in the audience, we'll mention observational trials a couple times throughout this episode. Uh, these studies are where we watch group of patients and subjects and look at what they've been exposed to just in everyday life, in this case, GLP-1 agonists, and then see if they have increased risks of a certain outcome, in this case, hair loss. Now, what's tricky here is that these can only show an association they can't control for other potential causes. And there could be lots out there.
00:05:37 Sara Klockars:
Yeah. And then just to point out too, that on the other hand, randomized controlled trials have less of this issue of alopecia or hair loss. So they actively assign people to either the drug or the placebo to help control other possible causes. So in one trial with tirzepatide, About five percent of patients reported hair loss, compared to less than one percent in the placebo group. Uh, in another trial with semaglutide, about three percent of patients reported hair loss, compared to one percent in the placebo group. So just keep that in mind that these studies didn't necessarily calculate whether these adverse reactions were statistically significant. Um, but they were just a tad bit higher in that in the GLP-1 agonist groups.
00:06:29 Steve Small:
Yeah. So there is a possibility there. And with all this evidence, I believe none of these studies controlled for genetic causes, for example, of hair loss. Things that I'm thinking of like male pattern baldness.
00:06:39 Sara Klockars:
Right, right. And then we also have to just keep in mind that nutrition plays a role in hair growth. And you know, if people don't get enough nutrients then we may see hair loss. We see this with some other disease states. Um, there there's a thought that with GLP-1 use, there's this abrupt change in eating patterns. So that leads to the less nutrients for hair growth and that sudden weight loss. So this can put stress on hair follicles, which results in diffuse thinning and shedding of the hair. The formal name for this is called Telogen effluvium, which is usually reversible but may take some time for hair regrowth.
00:07:20 Steve Small:
Okay, so that's interesting. It may not be permanent. I'm sure that's kind of a a relief.
00:07:26 Sara Klockars:
Yeah. And then to make it even more complex, there are some reports where hair growth improved with GLP-1s. So there are some certain rare hair conditions. And one theory is that there's this improvement in blood circulation to the scalp. Or perhaps it's that anti-inflammatory property of GLP-1s that may benefit some of those inflammatory scalp conditions. But honestly, it's just really too soon to know.
00:07:55 Steve Small:
Yeah, well, this is feeling clear as mud, but thank you so much for sharing your knowledge there. A really good data there and I'm really interested what Don's gonna think. We'll see what happens. Thank you so much.
00:08:06 Sara Klockars:
Thanks for having me.
00:08:11 Don Weinberger:
Wow. Thanks, Sarah. Interesting stuff. I agree this one is tricky. Uh, for this verdict. Steve, are you thinking what I'm thinking?
00:08:21 Steve Small:
I think so, Don. Something we really haven't done before. So for this claim that GLP-1 agonists can lead to hair loss, the verdict is. Evidence is mixed.
00:08:34 Don Weinberger:
So you could say the data are a little hairy here, right? Uh, so hairy, in fact, that we had to introduce the new verdict. The evidence is mixed. Yeah, it's too soon to say. Hair loss is a definitive side effect, but current evidence suggests this is something to watch out for.
00:08:52 Steve Small:
Yeah, quite the head scratcher here. Don and I liked Sarah's point about nutrition with this. Even though, uh, we're trying to lose weight here, patients still need to have adequate, well-rounded nutrition, so things like hair loss and hair growth aren't affected, right.
00:09:08 Don Weinberger:
And we can help patients weigh the use of hair loss treatments, such as minoxidil and biotin as a possible option if patients are losing hair. But keep in mind we don't have direct evidence yet that these help with hair loss related GLP-1s.
00:09:24 Steve Small:
Yep, that's a really good call out here and use our Treatment and Prevention of Hair Loss chart for a list of possible options to think about. And before we get into our next claim, if this episode is helping you cut through the noise, here's something to make your professional life a little bit easier.
00:09:38 Don Weinberger:
And already subscriber? Don't forget to claim CE credit for this episode.
00:09:42 Steve Small:
And if you're not a subscriber yet, or just think about upgrading, access your trusted clinical insights and more and save ten percent with our exclusive listener promo code one zero two five at checkout.
00:09:56 Don Weinberger:
Yeah, who doesn't love to save money? Right? Steve around the holidays to boots and details and links are in the show notes, so do not miss out. And with that, ready for another claim?
00:10:07 Steve Small:
You betcha.
00:10:08 Don Weinberger:
This one? Yep. Has got people talking for a whole different reason, as men can develop erectile dysfunction or ED from GLP-1 agonists, and this is based on increased reports to FDA and other adverse effects databases that suggest increased erectile dysfunction, which even one agonists of actual studies based on these databases did suggest a risk.
00:10:31 Steve Small:
But we know that case reports aren't really strong evidence here. And observational studies, as we said earlier, struggle to control for issues that affect the outcome.
00:10:40 Don Weinberger:
Yeah, and I'm really glad you said that. You know, for example, one of the studies had an issue, semaglutide Group had a higher body mass index than the control group.
00:10:49 Steve Small:
Yeah. Could that be why they had higher rates of erectile dysfunction? Who knows based on how that was designed.
00:10:56 Don Weinberger:
Yeah, right. So in fact, the majority of evidence we have shows that GLP-1 appear to improve erectile dysfunction and sexual performance. And we're talking about several observational and randomized controlled studies here. So stronger data overall.
00:11:13 Steve Small:
Yeah. And this makes sense since we know that obesity diabetes cardiovascular disease can affect men's sexual performance. So it makes sense that addressing these factors, perhaps by using a GLP-1, can help improve a patient's sexual health. And these might also be confounding factors when I think about it, since patients with these Ed prone conditions are more likely than to use GLP-1 agonists. So something to think about.
00:11:38 Don Weinberger:
Yeah. Great points. And I even found a recent randomized controlled trial in men taking dulaglutide specifically looking at sexual performance. And it didn't find a difference, albeit the study was small, I think it was twenty four patients. Okay. But it still offers some more reassuring evidence since it's tried to control for those confounding factors. And with that, let's go ahead and circle back to our claim, which is men can develop erectile dysfunction from GLP-1 agonists. And the verdict is. Rumor with conditions.
00:12:18 Steve Small:
Yeah. This rumor might need a little bit more support before it rises to the level of truth here. But keep in mind that although GLP-1 agonists might not be the cause per se, patients may still have sexual performance issues due to their obesity, diabetes, cardiovascular disease. So it is likely some men may need Ed treatments like sildenafil to help even while taking a GLP-1.
00:12:41 Don Weinberger:
And since that related notes, there has been case reports of decreased libido in women. But we don't have clinical trials looking at this, so evidence isn't really robust.
00:12:52 Steve Small:
Yeah, we'll have to wait and see. And we have a helpful chart for men managing erectile dysfunction that reviews various causes of Ed and medication options to treat it. So take a look at the show notes or description we've linked directly to that resource in pharmacist's letter, pharmacy technicians letter, and prescriber insights, as well as our Treatment and prevention of hair loss chart. We mentioned earlier.
00:13:14 Don Weinberger:
And if you aren't a subscriber, don't miss out on these resources. Sign up today to stay ahead with trusted insights and tools right now.
00:13:22 Steve Small:
This next claim is a serious one, and before we move on, we want to let listeners know that the next segment will discuss suicide and mental health. So if this topic is sensitive for you, please take care of yourself and feel free to skip ahead. And if you or someone you know is struggling, help is available, call or text nine hundred eighty eight or check out our show notes for more resources. So this claim is GLP-1 agonists increased risk of suicidal thoughts.
00:13:50 Don Weinberger:
So I remember in early twenty twenty four, uh FDA released a safety communication saying that they received several reports of suicidal ideation or action with GLP-1 agonists, but FDA's review of available evidence could not show a causal link, especially since the number of reports were really so limited.
00:14:13 Steve Small:
Yeah, and despite this, the labeling on Wegovy and other GLP-1s approved for weight loss do mention suicidal behavior as a warning. But keep in mind when you look closely at this warning, it states, quote, suicide and ideation have been reported in clinical trials with other weight management products. So they make that clarification there, right?
00:14:34 Don Weinberger:
Right. So that's really interesting. Uh, then what is the actual evidence for this concern?
00:14:41 Steve Small:
Yeah. Looking at this, initially there was a key case control study that came out in twenty twenty four, in the journal nature that looked at depression, anxiety and suicidal behavior in patients taking GLP-1 for weight management. And it looked at one hundred and sixty thousand patients and did show a one hundred and six percent increased risk for suicidal behavior with GLP-1 use.
00:15:05 Don Weinberger:
That's definitely concerning.
00:15:07 Steve Small:
Right? However, keep in mind this study didn't account for other important factors, such as patient compliance with the regimen, other medications perhaps the patient was taking that could affect this. So a lot of gaps that this couldn't cover.
00:15:21 Don Weinberger:
Right. It's a good point. So it comes down to were they even taking that drug properly.
00:15:27 Steve Small:
Yeah. We always have to think about that with these studies. And plus since that time we have several stronger studies that suggest there isn't an increased risk with GLP-1 agonists. For example, I found several large meta analyses of studies where they grouped and assessed several prior randomized controlled trials and sort of lumped them together. And those didn't show any increased risks. So pretty robust data there. So based on that, when it comes down to this claim that GLP-1 agonists increase risk of suicidal thoughts, the verdict is. Rumor. Obviously, the labeling of these meds is still pretty cautious on this, which is understandable, but I'd argue that even with this reassuring evidence that we talked about that GLP-1 aren't associated with suicide, we should honestly warn any patient about mood changes, depression, or suicidal ideation with any drug and refer them to help ASAP, such as contacting the crisis line at nine hundred eighty eight we mentioned earlier to keep them safe and of course, stop the med if there ever concerns for any of these symptoms.
00:16:35 Don Weinberger:
Yeah, all great points, Steve. And prescribers should continue to carefully weigh the benefits and risks of using weight loss products in patients with a history of suicide attempts or act of self-harm. Until we know more.
00:16:47 Steve Small:
Yeah, that's a really good approach. Also, keep in mind that evolving evidence even suggests that GLP-1s may improve outcomes for certain psychiatric conditions, things such as substance use disorders. But we do need to know more before we apply this data to practice.
00:17:02 Don Weinberger:
Okay, great. Okay. So shifting our lens to another hot topic, uh, this next claim is all about vision. So the claim is GLP-1 agonists are associated with blindness. So a twenty twenty five study linked GLP-1 to neovascular or wet age related macular degeneration, known as a. This is where the blood vessels grow abnormally under the retina and become leaky fluid. This leads to central vision loss in one or both eyes.
00:17:34 Steve Small:
Yeah, and I recall most GLP-1 agonists labels already warn about possible diabetic retinopathy with these meds.
00:17:41 Don Weinberger:
Right? So true specifically in patients with type two diabetes. Another study suggests that semaglutide might increase the risk of. Here we go. Non-arteritic ischemic anterior optic neuropathy or naion.
00:17:56 Steve Small:
Hmm. Is that pronounced naion?
00:17:58 Don Weinberger:
Perhaps your guess is as good as mine, but I'll keep an eye on on it. Uh, this is where blood flow is impaired to the optic nerve. That helps us to see. And this can lead to sudden loss of vision. It's often painless and develops in one eye over hours or days.
00:18:15 Steve Small:
Yeah. And this is all observational data like we talked about earlier, there aren't randomized trials that can prove GLP-1's necessarily cause these and other data show conflicting results. I even found some studies showing that these meds have protective effects. So that's interesting.
00:18:32 Don Weinberger:
It is. Yeah. And something else to kind of keep in mind is what these conditions are actually rare. Uh, for example, one in about one thousand patients aged sixty six or older with diabetes who use a GLP-1 for at least six months may develop that namd over three years, uh, compared to similar patients not on any of these medications.
00:18:52 Steve Small:
So not super common. Plus, it's well known that diabetes itself is a risk factor for naion and other eye issues.
00:18:59 Don Weinberger:
Yeah, very good point. It's hard to tease out. The truth is that it's too soon to say if they're more likely with certain GLP-1 agonists. And we don't know if dose, route, or frequency actually play a role. So going back to that claim, which is GLP-1 agonists are associated with blindness. The verdict is. True. With conditions, we definitely need more research where we could say that GLP-1 caused this. The data suggests it may occur, but with how rare these issues are, I would say the benefits generally should outweigh vision risks.
00:19:35 Steve Small:
Yeah, I'd agree with that even with this association. And also keep in mind that GLP-1s may cause temporary blurry vision due to fluid shifts we see as glucose levels decrease. And that's because this causes the eye lens to sit differently in the eye changing vision focus. And regardless, patient should get a baseline comprehensive eye exam before or shortly after starting a GLP-1 and repeat that examination at least annually, because that's frankly just good diabetes care.
00:20:02 Don Weinberger:
If eye problems occur while on GLP-1, that's a good time to weigh risks and benefits and decide whether to stop that med.
00:20:09 Steve Small:
Yeah. And counsel patients to watch and report any changes in vision right away. Since sudden vision loss is a reason to seek emergency care. Very very important there. And with that, let's scrub into a claim that's got the surgical team talking. Uh, GLP-1s should be held before every surgery to prevent aspiration. I love a good hospital topic and we may need to define aspiration here for folks. Uh, aspiration essentially means choking or inhaling food. And this is a concern during surgery. General anesthesia. Uh, just the meds themselves can increase vomiting risks. And you could possibly vomit your food during the procedure. And vomit can then enter into your lungs and cause pneumonia and other complications, potentially even death.
00:20:57 Don Weinberger:
That's charming. Uh, sorry. For lunch, I will put a disclaimer in the beginning to go over some neat topics with us.
00:21:05 Steve Small:
Right. But even with that, this is an important thing to think about since we know GLP-1 are slowing down stomach emptying. So it's logical to think that there's still food in there before surgery.
00:21:16 Don Weinberger:
Yeah. That is. And we have some evidence that surgery patients on GLP-1 are more likely to have the residual stomach for procedure, even after a typical pre-op fast.
00:21:26 Steve Small:
Yeah.
00:21:26 Don Weinberger:
This is why anaesthesia guidelines in twenty twenty three initially said to generally hold those GLP-1s before surgeries. Uh, but fast forwarding a little bit, I remember they released new guidelines on this, right?
00:21:38 Steve Small:
Right, right. In twenty twenty four, these guidelines were revised saying that generally most patients can continue their GLP-1 therapy around surgery, but patients with increased risk of aspiration may warrant holding the regimen on a case by case basis.
00:21:52 Don Weinberger:
Mhm. So going over some of the disease states like Parkinson's disease right. Yeah. Current nausea and vomiting. Or if patients are still titrating up, those GLP doses could warrant.
00:22:04 Steve Small:
Yeah, those are some really good common reasons. And this recommendation change is due to a recent large observational, uh, group of studies that showed, although that residual food can occur, they didn't translate into a higher incidence of actual aspiration events or pneumonia. So the food's there, but it isn't necessarily making people aspirate. Sure. So when it comes to this claim that GLP-1 should be held before every surgery to prevent aspiration, the verdict is. Rumor with conditions. So I would say that there's been a lot of bellyaching on this, but the reality is GLP-1s don't need to be held before every surgery, right?
00:22:48 Don Weinberger:
I also think that withholding a regimen may unnecessarily take away its benefits. Holding the regimen can be complex or lead to errors. So patient centered team based approach is important in making the decision.
00:23:00 Steve Small:
Yeah. To weigh those benefits and risks for sure. And pharmacists, especially in the hospital, can advocate having a risk based approach when deciding whether to hold a GLP-1 agonist before surgery.
00:23:11 Don Weinberger:
Sure. Let's migrate on to the other side of the counter here with community side. So pharmacists can help patients interpret pre-op instructions or paperwork from the prescriber if they have them. Spacing info might be included here. And we can help demystify it.
00:23:25 Steve Small:
Yeah. And if the decision is to hold the regimen, folks can refer to recommendations in our Perioperative Management of Diabetes chart that actually talks about timelines for holding GLP-1 beforehand depending on the product. And with all that, our bottom line truth today is that evidence continues to evolve around GLP-1 side effects. And our recommendation is to look at the evidence, not the headlines, where when helping patients really understand the risks here.
00:23:51 Don Weinberger:
Right. And we saw there were cases where evidence had flip flopped based on larger and better studies that have come out. It's important to stay informed about new data, and in the meantime, it's reasonable to be cautious and encourage monitoring while we learn more.
00:24:04 Steve Small:
I like that, and we at TRC healthcare are a trusted resource to help give you timely updates as more GLP-1 data come our way.
00:24:13 Don Weinberger:
And speaking of timely, it is time to reach into our Santa bag and pull out a truth question. So we had an audience question from our last episode about natural remedies for cold and flu that came in through our send a text link in the podcast Shownotes. They asked, Will apple cider help treat cold and flu symptoms?
00:24:36 Steve Small:
Yeah, it seems like patients are using apple cider vinegar everywhere now, from salad dressings to now medical treatments. But the quick answer here is no. Looking at our Natmed database, we don't have sufficient reliable evidence that it's useful for preventing or treating cough and cold symptoms.
00:24:56 Don Weinberger:
And you know what we recommend our patients to take natural meds. In a lot of cases, it's not that patients can't try it, it's that they shouldn't expect relief, right? I feel like we have other options with more evidence, such as cough lozenges and saline nasal spray.
00:25:14 Steve Small:
Yeah, and if patients want to try it, they should try small amounts such as thirty milliliters or two tablespoons per day for only a couple of days. We shouldn't be chugging whole bottles because large amounts and prolonged use is associated with issues things like low potassium levels in the blood or osteoporosis affecting our bones. Plus, it might increase the risk of hypoglycemia or low blood sugar if combined with diabetes meds. So we do have to think about that.
00:25:41 Don Weinberger:
Right. And great point, Steve. Uh, if you have any questions about GLP-1 agonists that popped into your head after losing this episode, send them in.
00:25:50 Steve Small:
Yeah. And we also use your suggestions to plan our episodes. So email us at rumorvstruth@trchealthcare.com or send us a text right from the podcast show notes.
00:26:00 Don Weinberger:
We know you have some great ideas for us to demystify.
00:26:03 Steve Small:
Definitely. And before you go, claim credit and access evidence based resources from pharmacist's letter, pharmacy technicians letter, or prescriber insights.
00:26:12 Don Weinberger:
If you're not a subscriber yet or want to upgrade, you can save ten percent with our exclusive listener code, which is one zero two five at checkout. Easy link in the show notes.
00:26:23 Steve Small:
Yep. And already a subscriber? Tap the claim credit link in the show notes, or search for CE organizer for this episode.
00:26:31 Don Weinberger:
And join us next time when we'll talk about claims around estrogen.
00:26:35 Steve Small:
Keeping with the hormone theme, I like it. Don, I see what you're doing there. And thanks for joining us on Rumor vs Truth, your trusted source for facts, where we dissect the evidence behind risky rumors and reveal clinical truths. We'll see you next time.
