Speaker 1 00:05 Lange, welcome to HelixTalk, a podcast presented by the Rosalind Franklin University College of Pharmacy. Narrator - Dr. Abel 00:11 This podcast is produced by pharmacy faculty to supplement study material and provide relevant drug and professional topics. Speaker 1 00:19 We're hoping that our real life clinical pearls and discussions will help you stay up to date and improve your pharmacy knowledge. Narrator - Dr. Abel 00:27 This is an educational production copyright Rosalind Franklin University of Medicine and Science. Speaker 1 00:32 This podcast contains general information for educational purposes only. This is not professional advice and should not be used in lieu of obtaining advice from a qualified health care provider. Narrator - Dr. Abel 00:47 And now on to the show. Dr. Sean Kane 00:51 Welcome to HelixTalk episode 13. I'm your co host, Dr. Kane. Speaker 2 00:55 I'm Dr. Schuman, I'm Dr. Hartranft, and I'm Dr. Patel, Dr. Sean Kane 00:58 and we're very excited to have Dr. Hartranft with us today, and we'll be talking about the American Heart Association and American College of Cardiology 2013 obesity guidelines, but focusing a lot on three FDA approved medications for obesity management. Speaker 2 01:13 So these guidelines were published along with the dyslipidemia management guidelines back in December last year, and getting started, just a brief overview the screening recommendation, obviously, are making sure we are checking patients height and weight and calculating BMI at least annual visits, and also doing the same with the waist circumference, unless they are on medication, such as atypical antipsychotics, for which we have to do additional monitoring. Dr. Sean Kane 01:39 One thing I liked about the guidelines. There are a few things I didn't like, but one of the things I liked was that they really coalesced all the data with regards to the importance of weight management and what impact that has clinically on a variety of different endpoints. And I think that having that in one document kind of almost as a review of why it's important to lose weight is one thing that they did really well. Speaker 2 02:00 And to get started with that, what you were just saying Dr. Kane is the guideline says, if the patient maintains a sustained weight loss of about three to 5% we can see the clinical results, meaningful results, and while looking at reductions in triglycerides, blood glucose, hemoglobin, even see which are also or patients who are at pre diabetes or at risk of developing diabetes. Dr. Sean Kane 02:22 What we found in the guidelines is they provide a reasonable recommendation for what is a reasonable goal for a patient's weight loss, and they say 10% of body weight over a six month time period. So if you're 200 pounds, that means a reasonable goal over a six month period is 20 pounds, which think having some reasonable goal is going to be much more effective than telling a patient that they need to get close to their ideal body weight, for example, which is probably an unreasonable goal for an overweight patient. Speaker 2 02:48 And you know, like you said, it's standard over six months of time, and not all the patients would stick to this resolution or goal for six months of time. So what those guidelines are also recommending is counseling, which includes lifestyle interventions, behavior modifications with the counselor for patients who are going to be on such therapies, or weight loss planning for more than six months. Dr. Sean Kane 03:11 So Dr. Hartranft, were there any dietary recommendations in the guidelines that struck you as more pertinent from a patient counseling standpoint, or something that you'd heard about that you thought was interesting. Speaker 3 03:22 Absolutely, you know, reading through the guidelines, I was impressed as you were, I think that the guidelines were pretty specific, that they gave us good, solid recommendations in terms of calorie restriction. When we talk to patients about cutting back, it's important we counsel them on cutting back appropriately, not going on a very low calorie diet, but rather for men, targeting somewhere around 1500 to 1800 calories per day, and for women, a little bit less, maybe 1200 to 1500 or, you know, alternatively, having them look at their diet for about a week or so, see where they're at, and then cut anywhere from 500 to 1000 calories from their daily total. So I thought that was very helpful. It's interesting to note that when you read through the literature, there's not really one particular diet or strategy that comes across as the absolute best. Dr. Sean Kane 04:09 I'm pretty sure the Atkins diet is the best, but continue. Speaker 3 04:13 You know, everybody's got their favorites, and I think as pharmacists, being so out there in front of patients, we're constantly being asked these questions about, what can I or can't I eat? What diet is the absolute best? And I tell everybody, the absolute best diet is the one that you can stick with, and that works for you and you can maintain because the Atkins diet might work for you know, your average caveman who really loves his meat, but some people will miss their carbohydrates, and so we need to talk to them about other diet strategies and consuming a variety of healthy foods that are high in fiber, high in nutrition, and just eating a balanced diet. Speaker 2 04:48 So obviously, we're going to talk about the medication in just a little bit. But you know, if the patients don't do well on the medications, or they fail the medications, or if their BMI is exceeding the use of the. Limit of, you know, medication use, then they progress to having bariatric surgery. So the guidelines recommend that if the patient's BMI is greater than equal to 40 or even, patient's BMI greater than equal to 35 plus have one of the obesity related comorbid conditions who are motivated to lose weight, and, you know, have not responded with the lifestyle intervention, behavioral modification, therapy, with or without, the pharmacotherapy, we can go ahead and consider the bariatric surgery. Dr. Sean Kane 05:27 So I think that's important to think about all of the different criteria that the guidelines laid out of who is an appropriate candidate for bariatric surgery. It's a motivated patient who meets certain BMI guidelines with or without some of the obesity related comorbidities, who has failed normal therapy. So this is not the first or second line therapy. This is someone who's actively been trying to lose weight, is very motivated to lose weight, as opposed to the quick one off wall is this, do the lap band procedure and we're done right, correct? Speaker 2 05:58 And a lot of this time, patients do come and ask me what, you know, diabetes patients that say, can I just go with the surgery and, you know, be off of the medications and lose all the weight? And like, they think that it's going to happen in two weeks, and it's not realistic. So I had to sit down with them and say, you know, no, you have to consider all the other aspects before you can be progressed to an option of bariatric surgery. Speaker 4 06:20 I think part of that is because with the nature of the surgery itself, there's a fair amount of compliance that is intensive in it in terms of modifying, you know, diet that's going to naturally occur due to the consequences of having maybe a reduced stomach volume, for example, and as well, some adjustments of even medications. And further, you may see changes in your existing regimen. So if somebody thinks that that's just going to be one and done type of approach taken. Dr. Sean Kane 06:44 So Dr. Hartranft, I know that when these guidelines were published, they may have been overshadowed a little bit by the lipid guidelines were published concurrently. So many of our listeners probably haven't heard of these new guidelines, but you know, I bet that they're very excited to hear about all of the pharmacotherapy guidelines and recommendations that were built into these guidelines, right, right? Speaker 3 07:03 Doctor Kane, you make a great point. It was kind of interesting the way these guidelines got overshadowed. But I will say obesity and obesity medications have really been in the news a lot over the last couple of years. In 2012 we had not one, but two obesity related medications approved by the FDA, and they were the first medications in 13 years that we had approved for this indication, so it was pretty big news. The drugs we have on the market right now. There's three of them that are indicated for long term weight loss, and that's orlistat, which is been on the market for a little while under the brand names Alli and Xenical. The new ones are lorcaserin (Belviq) and phentermine/topiramate (Qsymia), Speaker 2 07:44 and so much talking about the excitement of this new guidelines, we were hoping that the guidelines would review these medications and include recommendations as part of their pharmacotherapy intervention recommendation. But unfortunately, that didn't happen. So what they did is they stuck to expert opinion, and those are really general recommendation to consider pharmacotherapy in patients who have BMI of greater than 30 or BMI of greater than equal to 27 with at least one obesity related comorbid condition. And we've been saying whole lot obesity related comorbid condition, what we're talking about is hyperlipidemia, metabolic syndrome or diabetes itself. You also have to make sure that patients are again motivated to lose weight, not just, you know, relying on the pill to lose weight. Also have to make sure that they are seeing one of those behavior interventionist to continue their lifestyle modifications throughout the therapy. And also have to make sure those medications are FDA approved. So that kind of rules out all the over the counter advertisement and commercials that people have seen on TV. So off the bat, you want to make sure that you debunk that meat, that myth that they're not going to be able to use those agents because they're not FDA approved. And last but that's not the least, that recommendation is that the provider who initiate the treatment is well versed in the therapy and that they understand the potential risk versus benefit and then choose the patients accordingly. Dr. Sean Kane 09:09 So in thinking about the pharmacotherapy generally, in my opinion, the guidelines were a bit silent in terms of preferring one therapy over the other, or even providing a risk benefit analysis of one medication over the other and truly their recommendation is what is on the FDA labeling for the indication, which is BMI greater than 30 or BMI greater than 27 with obesity related comorbidity. So they're really just recommending that you evaluate the appropriate use in those patient populations for pharmacotherapy. So kind of moving on to the pharmacotherapy, I think there's a few common themes that are present with all three of the medications. Probably the easiest, most obvious one should be pregnancy category x, so Pregnant women should not be taking pharmacotherapy to induce weight loss. Some of our medications do have fetal harm, but the idea of causing weight loss during pregnancy is probably a bad idea in the first place. And then the other common theme is the indication. So all of these medications are FDA approved in the same patient group, which is the BMI greater than 30 or greater than 27 with a comorbidity like diabetes, hyperlipidemia or hypertension. Speaker 4 10:14 And I think within the class was when I look at these medications, they seem to fall within one of three classes. And with with any kind of weight loss, even over the counter ones. You have those medications that decrease the appetite, those that decrease fat absorption, as well as those that increase thermogenesis. So I believe the first one on our list is going to be lorcaserin (Belviq), and this is one of these that falls in the category of adjusting your appetite. So this medication is a Schedule IV medication, and that's going to be something we'll touch on in terms of potential side effects, but again, that's also going to limit its access. And the mechanism being as it works on serotonin receptors, it ends up being something that I perk up at being a psychiatric pharmacist. So this medication, though, unlike most of the ones that I work with, this one actually activates serotonin at its five HT to C receptors. The end result of this is that it results in satiety and decreases the overall food intake. So short, short story of it makes you feel more full. So this medication is approved, again, as Dr. Kane mentioned, we have very set criteria of approval, and they're all going to have the same wording of as an adjunct to reduce calorie diet and physical activity. No one of these medications is going to exist in a vacuum where you're sitting back and eating whatever you want and not exercising. Dr. Sean Kane 11:24 So we are going to discuss some of the efficacy of these agents. And I want to caution the listener that these aren't comparable data. So trial a with bell week should not be compared in terms of total amount of weight loss to another agent, because the patient populations could be very different. So it's an apples and oranges thing, Speaker 2 11:42 and with the different mechanism of action, as we would see as we progress through the podcast, is that maybe then, in that case, if patient fails one of the medication, you know, you can definitely go ahead and try the different medication too. However, they should not be failing on their efforts for diet and exercise modification. Dr. Sean Kane 11:59 So Dr. Patel, can you give me an idea of the clinical efficacy of lorcaserin (Belviq) that we saw in some of its clinical trials? Sure. Speaker 2 12:07 So this medication was approved based on three different trials. We have the BLOOM and BLOSSOM trials, which were done in a general patient population against placebo. And then we have the BLOOM-DM trial, which was done in patients who had baseline A1C of about 7 to 10% who were on metformin and sulfonylurea. In the BLOOM-DM trial again, there was lorcaserin against placebo. Similar endpoints were used looking at total weight loss, mean weight loss, 5% and 10% weight loss. And what we found is that patients in the lorcaserin group were more likely to achieve that 5% weight loss and greater than 5% weight loss, and they also achieved lower A1C, so the goal is less than seven. More patients in the lorcaserin group were able to achieve that. However, we noticed more hypoglycemia associated in the lorcaserin group, and that's because patients are continually losing weight, so hypoglycemia resulted from that. But the good thing about this trial was that the hypoglycemia was not severe or using coma, requiring hospitalization, or anything like that. Dr. Sean Kane 13:18 And that makes sense, right? So your insulin resistance is going to diminish as your body weight decreases. And the FDA noticed this, and it's, I think, a good thing that they ran a trial only for diabetics, and they created a warning in the packaging that says, hey, if you're a diabetic, watch your sugar. You probably will eventually need lower doses if you are successful in your Speaker 2 13:38 weight loss, absolutely. And it's a good thing, because we can back up on the anti diabetic medication, exactly completing the evidence from blue and blossom child again, there was again, lococerone against the placebo. We were looking at one year weight loss, you know, and then we're also looking at patients who were most likely to lose 5% or 10% weight loss versus the placebo. So what the child found out, patients in Doctor Seren group lost an average 5.8 kilogram of weight versus patients in placebo group lost about 2.5 kilogram of weight, so there was still little bit of placebo effect. Again, because these patients were very in a controlled environment, monitored for lifestyle interventions and etc, and that kind of leads to a question of external validity, how applicable the results are of this trials and to your actual patient population, right? Dr. Sean Kane 14:29 So in the trial, because placebo lost weight, in thinking about what was the actual effect of the drug, it was 3.3 kilograms, or about seven pounds, and again, thinking about that external validity, so in the trial, it's going to be very regimented, in the sense of, you have to do this exercise, or we recommend that you do this exercise. We're going to have someone counsel you on your diet, things like that. Whereas in real world, it's probably more likely going to be, Oh, you want to lose weight. Here's a prescription. Good luck to you. And I think that that's an issue that the guidelines address, saying, you know. Having the counseling is important, but if you can't achieve that amount of counseling, you probably aren't going to see the same benefit as what you saw in Speaker 3 15:06 these trials. Great. And I think that links into some of the monitoring that we see built into the patient labeling on this drug, and that is for patients who reached 12 weeks on this drug and haven't yet lost 5% of their baseline weight, it's recommended that they discontinue the medication, because they're probably not going to see benefit, and that may be partly because of the lack of patient compliance with the other aspects of this weight loss regimen, and it may just be that those patients aren't going to see benefit from the drug, but I think it's one of those things that you're right. Patients kind of look at these medications as a silver bullet, and they just take the pill and life is going to get better and the pounds are going to fall off, but that's not the case. Dr. Sean Kane 15:42 And thinking about the cost of the drug, it's more than $200 per month, so it's probably a good idea to consider discontinuation. If it's not going to be effective, has to be taken twice a day. It does have renal adjustment that in terms of dosing should be considered, and it also has some drug interactions that we should think about. So it's a 2d six inhibitor. That's a pathway that's used for things like coding, for coding activation to convert coding to morphine. It's used for beta blockers, certain beta blockers, Speaker 3 16:11 I always like to throw in the example of tamoxifen. My patients who are on Tamoxifen either for prevention of a primary breast cancer or for prevention of relapse of a breast cancer, they need there's 2d six to metabolize tamoxifen to its active metabolite, and if we're inhibiting that, my patients don't get their benefit. So I think it's important that everyone's educated about those drug interactions. And actually, Speaker 4 16:31 I'll chime in on my patient population as well. Your SSRIs, your selective serotonin reuptake inhibitors, your SNRIs adding norepinephrine, like venlafaxine, and your antipsychotics as well. Many of them are dependent upon CYP2D6 for some, at least some form of their metabolism. And so adjusting that, and again, we end up with unpredictable kinetics. Dr. Sean Kane 16:50 So then, in thinking about cost, potential drug interactions, dosing, the big reason that if it's not going to work is that you should discontinue therapy, is the adverse effect profile. So this isn't as bad, in my opinion, as some of the other agents, but it still has a pretty appreciable adverse effect profile that a patient should know about. The big ones that I think of probably the most common are going to be headache, dizziness, and then in diabetics, an issue with hypoglycemia that we talked about, especially in those who lose weight and have improved insulin resistance, Speaker 4 17:20 and I find interesting, again, very are a little less common, but some potential concerns about cognitive impairments, bradycardia and even elevated prolactin levels. And what that may involve is, again, it with the five HT receptor. I find this interesting, is that generally, so our medications that block five HT increase dopamine slightly, and so a medication like this would potentially do the opposite, and then by low if we lower dopamine, that increases prolactin. And so that would again explain why we have elevator prolactin as a concern, and it could lead to either go after rear or gynecomastia. But again, that's based upon potentially this mechanism, and then that also leads into some of the more rare but serious side effects, such as priapism, depression and serotonin syndrome, because, again, we are adjusting some of the balance of serotonin and dopamine. So we do want to be careful about other serotonergic medications that they may be on. Again, your SSRIs, your SNRIs, and then mono means TCAS, Bupropion. Dr. Sean Kane 18:14 I know we mentioned it earlier, but lorcaserin (Belviq) is a DEA Schedule IV medication. What was the reason for it deserving that labeling as a controlled substance? Speaker 4 18:25 I think, with this medication, what they noted was, in some studies, as well as some user reports, of those who had a history of abuse, patients who were taking four to six times the usual dose, had euphoria and hallucinations. And actually, some of these users had rated these hallucinations, for example, as being similar to those they experienced on, say, ketamine. Dr. Sean Kane 18:43 And I don't think it's that abnormal to think a patient might actually take four to six times the dose, given that it's a weight loss medication, if someone's especially if they're being successful with the medication, I don't think it's unreasonable for a patient to say, well, if I can lose a pound a week with one tablet twice a day, maybe I can lose even more with four tablets twice a day. So it's not out of the realm of possibility that a patient might abuse it unintentionally, with good intentions, but discover this euphoric effect that they could get out of the medication. Speaker 4 19:12 And I think Furthermore, there's, you know, additional concern about given the past history of medications in this class, about wanting to be extra careful about getting into approval and how it's scheduled, and I know that with Fen fan being an example, without this combination of fenfora mean, fentre mean that cause this valvullopathy as well as a pulmonary hypertension now that medication worked on serotonin 2b receptors and not the 2c receptors, but that being said, they still wanted to be very careful and more deliberate in getting This one to market and making sure it's well regulated. And due to that, there was a delayed, delayed approval pending an extensive safety evaluation. So the original studies didn't show a large increase, really, they didn't show any increase in valvuopathy. However, the original studies were not necessarily powered to be able to say so with a lot of confidence, and so there was again. Little bit of making this a slow process to make sure that this time when the medication hits the market, it's all right. And there are other ones that have been approved in Europe. They didn't make the United States. They wanted to see that if one gets approved, that we do Dr. Sean Kane 20:10 it the right way. So the second medication that was recently approved is phentermine/topiramate, which is a combination product and the brand name is Qsymia. And again, topiramate is an antiseizure or antiepileptic medication. The brand name is Topamax and phentermine brand name is Adipex; this medication class was approved decades ago for weight loss indication. Speaker 3 20:31 and it's still approved today, but it's indicated solely or as monotherapy. It's indicated only for short term treatment of obesity. This combination pellet should be noted, is approved for long term treatment of obesity. Dr. Sean Kane 20:44 So Dr. Sherman, how do these medications work? The combination product? Well, that's Speaker 4 20:48 what's interesting is, once again, we have a couple different mechanisms. This one falls into the third class. So we again mentioned the appetite suppressants, the change in absorption. In this case, we have the thermogenic potential. So phentermine acts as a stimulant, like in its increasing release of catecholamines, particularly norepinephrine. So what you end up seeing is essentially putting the way I describe when I'm counseling patients or talking to students, it is putting some sort of a stressor on the body that is allowing it for an increase in output. And then as well, is these. By working on some of these catecholamines, you can also see a decrease in appetite as well by stimulating the body in this way, there's less of a need to seek out these behaviors in reinforced atmospheres, such as through heavy eating. Speaker 2 21:30 So the addition of to pyramid actually is very interesting, because when the pyramid came out in the market, one of the huge side effects that they found out was anorexia, and so they don't know the mechanism behind how to pyramid exactly causes anorexia, but it again, it leads to that pathway of appetite suppressant, somehow, suppression, somehow. And so they threw in that, along with the Phantom in, we got two different mechanisms going over here, giving us maybe, hopefully, a little bit better weight loss benefit. Dr. Sean Kane 21:58 Seems like the next logical step would be to start using, let's say, chemotherapy, with its anorexic effects, as a weight loss drug, right? Speaker 3 22:05 Definitely, I think that a lot of patients could benefit from that careful monitoring required. Dr. Sean Kane 22:10 However, humorous to me that we are utilizing this adverse effect of an anti epileptic, which, as we'll discuss, has a lot of adverse effects that are pertinent, and we're just combining it with a stimulant and coming up with a new medication, I think that it's a slippery slope. Speaker 3 22:24 Well, of course, you point that out, Dr. Kane, and it's noted in the product labeling, this risk of seizures. And you'll see when we I'll talk about the dosing a little bit, but it's very important to note that the dosing on this medication is quite strictly laid out, and it has to be tapered both up and tapered down when a patient comes off of the drug, and it's because of this anticonvulsant property, and even patients who don't have a baseline seizure disorder are going to have their seizure threshold lowered when they abruptly stop this medication. And so we see that it's dosed once a day in the morning, and for the first two weeks, the patient should be on the lowest dose. After that first two weeks, we increase to the medium dose, and they remain on that for 12 more weeks. At that point, if the patient's had at least 3% weight loss from their baseline weight they can remain on that same dose for a long time. If they have not achieved at least 3% baseline weight loss, the dose should be increased, and there's another step up for two weeks, and then after that two weeks, they can go to the highest dose. As I said, when they come off of the medication, it needs to be tapered down in much the same way. So there's no guidelines in the product labeling. But of course, I would recommend maybe that same two week step down to each dosing. Dr. Sean Kane 23:40 So I think that's interesting, that this is only one of the three that we're going to talk about today that has a tapered schedule, where you kind of taper to weight loss goal, almost, whereas the other two medications that we'll discuss is kind of a fixed you get it or you don't get it, and that's kind of all, all there is. So I'm thinking about the efficacy of this. And again, we're not comparing apples and oranges, because the trials are different patient populations, but in obese patients versus placebo, over a year, patients on the lower dose lost about an additional 3.5 kilograms or eight pounds. In the higher dose, they lost 9.4 kilograms, or about 20 pounds with the higher dose medication. In a separate study of obese patients who also had an obesity related comorbidity, they lost an additional 6.6 and 8.6 kilograms with moderate and high dosing. So you can see that there's a dose dependent effect. You can see that you do get what I would consider a pretty good weight loss comparative to what you know, diet and exercise and things like that can achieve on its own. So it's not that these medications don't work or anything to that effect, but I think the tolerability of these medications is something that we probably need to think about. They do have adverse effects that patients need to know about. And in the packaging, you'll see that they do have a pretty high discontinuation rate, either because of lack of efficacy or because of the adverse effects Speaker 4 24:53 that we see. And Dr. Kane just to touch on something you stated before about the external validity of these trials, once again, in both of these studies. Use the placebo arm here, did lose weight compared to 1.6 kilogram weight loss in the original study, and then the follow up study 1.2 kilograms. So once again, the setting in which these patients are at is there's gonna be a little bit of a tendency towards weight loss that may not be necessarily replicated in the average population that may be receiving this medication. Dr. Sean Kane 25:17 So Dr. Patel, are there any adverse effects that really stick out to you in terms of what we see with phentermine/topiramate (Qsymia)? Speaker 2 25:24 So I cannot wait to talk about all the possible laundry list of side effect that's coming off with this medication, and hopefully this should deter a lot of physicians from using it and just go the natural route of doing exercise and diet. But to start out, with Topiramate, you know that medication impacts the central nervous system. So you're going to deal with patients with mood and sleep disorders. And I'm sure Dr. Schuman probably has seen this, where patients can complain of insomnia, beginning or initiation of depression, or even worsening of depression if they already had it, anxiety, irritability. There's some impact on cognition as well. And again, this is all two pyramids doing and going along with phantom means, you know, amphetamine like stimulant effect. What it would do with all those release of catecholamines in the body, it's going to cause increase in heart rate. So there has been incidents of tachycardia to 11.9 to about 19.6% of the time. And so you have to be using caution in patients who have underlying cardiovascular condition. So let's Dr. Sean Kane 26:25 just think about that. One in five patients, their heart rate, basal heart rate, is going to go up 20 beats per minute or more. That's a pretty significant increase, going from a due to 100 or probably less likely 100 to 120 that greater than 20 increase. That's a lot. That's a pretty big response to the stimulant effect of the phentermine, absolutely. Speaker 2 26:44 And with this increased heart rate and all the release of catecholamines, there is a risk of increase in blood pressure as well. And we're talking about this medications approved in patients who have obesity plus one of the conditions like hyper pressure, diabetes. So we have to be careful in who we pick and to use this medication for. Dr. Sean Kane 27:02 I think this is a pretty crazy adverse effect, so paresthesia, so tingling of the face, the hands or the feet and the placebo arm. It was about 2% in the treatment arm, almost 20% so think about that again. One in five patients who take the medication will have tingling on some part of their body that they wouldn't have had had they just done run of the mill, diet and exercise with no additional medication. And then a fairly rare Speaker 4 27:24 An ADR that can come up is due to the mechanism of topiramate as a carbonic anhydrase inhibitor. What you can actually see is a little bit of a loss of bicarbonate. And then that can be manifested as a type of hyperchloremic acidosis that you can occasionally see. So every once in a while, if you're monitoring this, you may see an increase in their chloride if you're doing a chem7 or basic metabolic panel; those kinds of things you may just want to monitor for and be aware of. It may not need intervention, but again, just keep an eye on it. Speaker 2 27:51 causes a lot of Gi side effects. To be talking about constipation, dry mouth, metallic taste, though other taste sensation as well as nausea and other GI discomfort too. And Dr Speaker 3 28:05 Schuman going on with what you said about the metabolic disorders, there is a lot of monitoring that's built into the labeling for this medication. So not only the electrolytes, bicarbonate, chloride, potassium, other electrolytes, we also should be monitoring glucose. We should be monitoring patients cardiovascular we talked about the increased heart rate blood pressure, and of course, I don't think we've said it out loud, but it should be assumed that with all of these weight loss medications, we need to regularly be monitoring patients weight in a physician office, and also they should be monitoring it at home. But I think that's one thing that stands out to me about the formulation of phentermine and Topiramate is that there is such a significant burden for monitoring compared to some of the other medications that we've looked at, and patients need to be aware that if they're going to be on this drug, that they'll be having to go into their physician pretty regularly for this type of monitoring. Speaker 4 28:55 And then one other quick monitoring, or pearl on this medication, is if you do have a history of glaucoma. Any of these sympathomimetic types of medications can cause a worsening of glaucoma or provoke it. So you just if you have glaucoma and it's being treated, just want to be aware of that for further monitoring. It may worsen some of your symptoms. Dr. Sean Kane 29:13 Finally, just some housekeeping issues. This is DEA schedule four because of the phentermine component. And then, in terms of cost, it depends on the dose that you're at. Again, it's that sliding scale dose, and it's anywhere from $180 to $240 per month. And again, it's at once daily medication that you'll be taking. So given that adverse effect profile, I'm sure there can't possibly be another medication on the market that could have worse adverse effects than what we just went through with that laundry list. Unknown Speaker 29:40 Are we talking about or list that we may be Dr. Sean Kane 29:43 Oh, no. So what is orlistat? Speaker 3 29:45 Well, orlistat, the drug that's been on the market for the longest out of this group that we've been discussing. It's been on the market as the prescription drug Xenical for over a decade now, and just a couple years ago, the over-the-counter version Alli was approved. The difference is dosing. Xenical is 120 milligrams three times a day, and Alli is half that dose, 60 milligrams three times a day. And of course, this is the one that's famous, because patients should be advised not to wear white pants while they're on this medication. Dr. Sean Kane 30:15 Well, if it's after Labor Day, I think we understand why. But aside from that, that Speaker 3 30:20 has to do with the mechanism of action. Orlistat works by inhibiting both gastric and pancreatic lipase enzymes in the GI tract. Normally, lipase takes our triglycerides that we eat and consume in our diet and breaks them down into free fatty acids, which then cross the intestinal lumen. Orlistat works by inhibiting the breakdown of those triglycerides, and instead of being absorbed into our body, they pass out through our stool, and in high amounts, that triglyceride content can cause some problems such as oily stool, increased defecation side effects are listed as oily Flatus. It's really just problematic from a GI standpoint for our patients, and I worry sometimes that, especially with the over the counter version, patients may pick it up without fully comprehending what they've gotten themselves into. Dr. Sean Kane 31:11 So just to briefly touch on a few of those adverse effects. Again, one in five or 20% of patients that take this medication will have oily spotting, fecal urgency, oily stool, oily evacuation, some kind of pretty severe form of Gi intolerance of the medication. Speaker 2 31:28 So yes, there are all the bad side effects, but then what's the good side of it? What's the amount of weight loss that patient achieved with this medication? Speaker 4 31:37 And I think that's kind of interesting, that this medication, it may seem well, what you do is, one of the things that's counseled this medication is that you want to go ahead and adjust the amount of fatty acids you consume in your diet, and so you need to make those adjustments to avoid and mitigate the risk of the side effects. So what then it seems, or somebody may think, well, if I'm decree, if I'm being forced to decrease the amount of fat I'm getting, is this, is that all this medication is doing is providing an incentive to not eat fats. And actually the medication works beyond that, there's Yes, it does cause you to you do want to cut down on the fats, but it actually causes a weight loss that's more than what would be seen from that decrease in calories. So it's an additive effect, more than just the sum of what you're losing. Dr. Sean Kane 32:15 But let's be honest, in addition to this additive effect, there is a strong psychologic component of not eating fat with it as well, which certainly helps with the weight loss. So it's hand in hand, Speaker 2 32:26 because people want to lose weight, but at the same time they don't want to lose weight the entire time sitting in their Dr. Sean Kane 32:30 bathroom, right? I mean, I'm pretty sure I would not go to McDonald's if I had just taken this medication. So I think that that thought alone, especially if you experience the 20% of patient population where they have the adverse effect, it's likely that they're going to think twice about a high fat meal or an inappropriate meal for what their diet plan is, given that they've experienced or know of the adverse effects that are likely with the medication. Speaker 4 32:53 Since we are talking about some of the concerns about fat absorption, there is an injuries and counseling with this medication is that you also when you are taking it, and it's dosed three times a day, 60 milligrams, if it's over the counter, or 120 milligrams prescription. But you want to go ahead and take it with a multi a daily multi vitamin, due to the fact that you may be have difficulty absorbing some of those fat soluble vitamins, so that A, D, E and K, you have to be careful of the amounts that you absorb. And particularly, you would you know, if you're somebody that's on a blood thinner such as Coumadin or warfarin, you may just have to be aware of the fact that that medication you know may change your absorption of vitamin K with could then adjust your sensitivity to your Warfarin dose. Speaker 2 33:34 One other thing that I want to mention about Xenical is that the cost, and because we compared other medications it is a little bit more costly. So if you're going the route of the prescription product, which is 120 milligrams, the cost is anywhere about $500 a month. And if you're going with the generic over the counter product, like a 60 milligram tablet, you can complete your one month therapy in about 50 to $60 we talked about all the possible risk that comes along with this medication. If I were to allude to the fact that benefits in clinical trials and patients who have used this medication for over one year, we have seen weight loss about six kilogram which equates to 13.4 pounds, versus patients who are under placebo group still lost 2.6 kilograms, about 5.8 pounds. So the net benefit was about 3.4 kilograms with or less that versus placebo. Dr. Sean Kane 34:28 And then again, thinking about some of the drug interactions, in addition to the impairment of fat soluble vitamin absorption, the packaging does was specifically cyclosporine, which is an immunosuppressant, Synthroid or levothyroxine, and a few other anti epileptics and other medications that either because of the fat breakdown inhibition or because of direct inhibition of the drug itself, you get basically less drug that gets absorbed into the body. So I'm kind of reviewing all three of the pharmacologic options that we have for weight loss. I think it's a. Important to counsel patients on the anticipated amount of weight loss based on the clinical trials, which, in my opinion, is kind of the best possible circumstances. Where you're in a controlled environment, you have highly motivated people to get you to lose weight, to make their drug look better. And in these very controlled, probably externally invalid studies, the typical weight loss on top of what you'd get from placebo, which was diet and exercise alone, was anywhere from about seven maybe up to 20 pounds. But I think that 20 pounds is a pretty big outlier. So something about 10 pounds, I think, is a reasonable counseling point to tell a patient you're probably going to lose between five and 10 pounds on this medication, assuming that you do diet and exercise, based on the clinical trials that we have. Speaker 4 35:42 And the first medication we talked about is laurica sarin Bell v is going to be the brand name of that product. And the good thing about it is it can work to lower weight by decreasing your appetite. The bad of it, though, is this medication can have some drug interactions by inhibiting your cytochrome 2d, six liver enzyme system, so thus it could change a metabolism a few of your other medications. Speaker 3 36:02 The second medication we talked about is Qsymia (phentermine/topiramate). And the good thing about it is it's a combination medication, so you're getting two different mechanisms to help you lose weight. But the problem, and the big take-home message that I would like to emphasize is the issue of tapering: it has to be both tapered up and tapered down. Patients cannot simply abruptly stop this medication, or they're going to be at risk for a seizure. Speaker 2 36:25 And the last medication we discussed is generic name or less that it's available in two different forms, behind the counter at zenekal and over the counter as ally. And the biggest thing I would like to emphasize with this medication is the potential higher risk compared to the benefit that comes along with that, a few of them being, you know, increased oily evacuation and defecation. So I would say prescription of adult diapers should also go along with the prescribing of as I call or ally Dr. Sean Kane 36:55 with that, I sign off. I'm Dr. King, Unknown Speaker 36:57 I'm Dr. Schumann, I'm Speaker 2 36:58 Dr. Hart raft, and I'm Dr. Patel. And as always, study hard. Narrator - Dr. Abel 37:04 Thank you for listening to this episode of HelixTalk. For more information about the show, please visit us at HelixTalk.com you.