PodcastRx Ep. 48 - Talking Tirzepatide and Weight Loss with Chris Bender, PharmD, BCACP

podcast RX podcast RX podcast RX podcast RX podcast RX welcome to podcast RX from Diamond Pharmacy a show featuring The pharmacists in Personnel behind the nation's largest Correctional Pharmacy provider while we talk primarily about clinical and Regulatory topics affecting the institutional Healthcare clients we serve we'll also occasionally get into the stories behind the people moving our company forward this isn't just a pharmacy podcast and you don't have to be a clinician or a pharmacist to enjoy [Music] it for this final episode of 2023 we welcome back regular contributor Chris Bender from the Optics clinical team

to pick up our conversation about glp1 weight loss medications with the FDA approval of Zep bound or tepati for weight loss in November the profile of these potent and high-profile medications only continues to rise we take a look at tepati how it compares to semaglutide what the clinical data shows for its potency and what promise it shows for obese and overweight patients we also discussed some exciting new weight loss medications and development and what all this new drug development and approval could mean for the future of bariatric surgery all these topics and more on podcast

RX I'm Adam [Music] Campbell hello Chris Bender it's good to have you back on podcast STX as always how are you today oh hey good morning Adam I'm doing well hopefully you are as well it's always a really nice day whenever I get to chat with you it's always good to be back on the Pod absolutely and always good to have you and you know Chris we're we were reminiscing before we started recording here that just about a year ago if you can believe it we recorded an episode devoted to glp1 agonists and weight loss

with a focus on semi glutide in particular we were looking at how glp1 Agonist like o zic and wovi were not only effective at weight loss and diabetes management but also having a bit of a cultural moment uh as social media influencers and celebrities were swearing by these drugs and helping to drive demand and shortages of those drugs even if maybe those celebrities might have been using them in an off-label fashion but that's a different conversation either way medications like OIC like wovi were essentially a phenomenon and really continue to be almost a year after

our discussion we're seeing the profile of weight loss drugs continue to grow with the FDA approval of Zep bound on November 8th Zep bound which I can't help but think is a terrific name that either conjures up visions of Airship travel or going to see Leed Zeppelin is a trade name for tepati which unlike semaglutide is a dual acting glp1 and Gip receptor Agonist more on that in a bit it is a once-weekly injection and the dosage must be increased over 4 to 20 weeks to achieve the target dosages of 5 milligram 10 milligram or

15 milligram once weekly maximum dosage of Z bound is 15 milligrams once weekly tepati was first approved by the FDA in 2022 as munaro and used to reduce blood sugar and people with type two diabetes Zep bound is the version of tepati specifically approved for weight loss in obese patients with tepati showing improved weight loss numbers over semi glutide in clinical trials it's entirely possible that tepati will be a phenomenon of its own so Chris with this recent approval of Zep bound I wanted to keep our conversation going about these weight loss agents and get

a sense for both the basics of how they work and what kind of impact they'll continue to have moving forward so to start as we often do and what I know you like to do let's build up from the basics how exactly does tpde work for weight loss in contrast with semaglutide yeah so first fantastic introduction Adam as always um so I'm excited to get into this uh this topic with you and revisit it today so tepati actually works exactly the same as semaglutide when it comes to weight loss both drugs activate the glucagon like

peptide 1 receptor or glp1 receptor for short when the gp1 receptor is activated you know the body more effectively produces insulin in response to food intake it also decreases the body's own production of glucose which eventually goes on to become blood sugar uh it slows down the GI tract so food stays in the gut for longer and it increases our feelings of satiety or in other words feeling full it's these latter two that are responsible for the weight loss effects of these medications namely they slow down the gut and they make you feel Fuller for

longer effectively decreasing uh one's overall food intake now in addition to activating the gp1 receptor tepati also activates the Gip receptor which doesn't have any additive effects from a weight perspective however it does provide additive effects with regard to insulin secretion so from a diabetes perspective this dual mechanism provides additive benefits uh when it comes to glucose control now additionally GP activation acts almost as a safety mechanism in the fact that when blood sugar goes too low GP can actually stimulate glucagon which in turn can raise blood sugar levels so the Dual mechanism of tepati

uh makes it not only more effective for blood sugar lowering but also somewhat protective from going too low which is nice who exactly is Zep bound approved for I would assume it's very much the same as wovi it is so zound zound is approved for adult patients who are either obese which FYI is a BMI of 30 or greater or overweight individuals uh which is a BMI of 27 or greater who have at least one weight related conditions so such as cardiovascular disease dyslipidemia hypertension uh obstructive sleep apnea or type two or type two diabetes

so like I said this is the same criteria that we see with existing weight loss medications and I should say uh I would just like to delineate that there's essentially two buckets of individuals who this is approv for you can either get this medication if you are obese uh flat out or if you are overweight you must have one of those uh weight related conditions so given the increasing prevalence of you know both obesity as well as those chronic conditions you know I think it's pretty reasonable to believe that zet bound among others in this

category are applicable to a pretty broad swath of the US population something that I misunderstood um when I was researching these initially I thought Zep bound and its counterpart monjaro zip bound was the higher dose version of that but that's not the case right right and that was actually interesting to me as well uh because we saw that with we saw that construct with saxenda uh which is L glutide and um uh and wovi which is semaglutide those weight loss medications were both a approved for weight loss at a higher dose than what they were

approved for for their diabetes indications um with the mangaro and zet bound um situ pairing they're actually both they're approved the mjar is approved for diabetes and zound is approved for weight loss both at the same dosing so that was a very interesting Dynamic to see in comparison is there any reason behind that in particular because the other two are clearly different higher dose versus lower dose versions um is there any other reasoning behind that honestly from my reading of it all it just basically comes down to the fact that it appears that tepati is

is somewhat more potent than semaglutide and L glutide so it simply didn't need to be given at a higher dose like the doses that they were using for diabetes were already potent enough that they didn't need to kind of dial the knob up anymore for additional weight loss effect well you mentioned potency tepati is more potent than semaglutide what is the clinical data shown in terms of this potency um weight loss efficacy everything how does this compare to what's come before right so there was actually a major clinical trial published last summer uh that showed

the robust effects of tepati when it was used for weight loss in this trial the average weight loss was 31.5 to 53.7 pounds obviously this depended on the dose of the medication with the vast majority of partic ipants losing at least 5% of their Baseline weight which is something of a gold standard marker to demonstrate um individual's response to any weight loss medication now a weight loss of 31 to 53 pounds is obviously fairly substantial this equates to a 15 to 21% reduction in the participants's Baseline body weight so we're talking about losing up to

a fifth of your body weight uh potentially when using Zep bound now the next closest comparator is obviously wovi which demonstrated an average weight loss of 22 to 27 pounds again depending on the dose that was used with the majority of participants losing at least 5% of their Baseline weight now what's important to highlight here is that the trial for Zep bound was slightly longer than typical trials for weight loss drugs so it was 72 weeks versus 52 weeks which is more of your traditional um trial duration for weight loss drug so in that sense

yes the numbers for uh the weight loss numbers for Zep bound may be somewhat inflated but I will note that when I looked at the data the majority of the weight loss was actually attained by week 52 so it does seem as though um like we said before it does seem as though Zep bound is the more potent of the two now the other gp1 Agonist as I mentioned saxenda demonstrated less weight loss so was the the lesser of the three glp products currently available it demonstrates average weight loss of 8 to 11.4 pounds over

52 weeks with only about half of participants losing at least 5% of their Baseline weight now these numbers are are somewhat more comparable to what we see with the oral treatment options um of which there are many uh but they're just as important to review because in some cases insurances may require a trial of oral therapy prior to injectable therapy uh simply because of the lower cost associated with these oral therapies so to review uh we have DL proon which sort of a cousin of the anti-depressant uh buproprion or Welbutrin uh honestly it's an older

drug and it's not super commonly used we have fenine which is somewhat commonly used uh it's been in use for over 60 years uh we do have a newer combination uh which pairs fenine with Topiramate which is a seizure medication uh sold under the brand name cmia we have a combination of nxone which of course is a drug used to treat opioid and alcohol use disorder combined with biopron again like I said is an anti-depressant sold under the brand named contrave we have orat sold under the brand named zenal which interesting about this one is

it basically it basically prevents fat absorption in the gut uh and then finally we have plenity which might be the most interesting because it's not actually a drug at all um so it simply absorbs water in the gut and it expands in the gut which ultimately creates a sense of fullness which is what we're looking for now with most of these oral medications you're looking at a weight loss of somewhere around 10 PBS over the course of the year although cmia actually demonstrated a little bit higher with a weight loss of up to 19 pounds

in its clinical trial which is a bit closer uh to that scene with wigi you know Chris despite all the impressive numbers and comparisons of Effectiveness down the line it's important to keep in mind the impact of the non-pharmacologic factors in the overall success of these medications that is they need to be combined with the healthy diet exercise and lifestyle overall yeah I don't think that can be stressed enough and just an interesting tidbit um kind of you know getting into the clinical trial weediness of it all that's why you see higher weight loss in

the weight loss trials as opposed to the diabetes trials because for example when we were looking at you know not not we as in me personally but you know when in the clinical trials that assessed M jaro for example for diabetes the weight loss was prominent obviously but it wasn't as robust as what was S as was seen in the Zep bound trials and as we said before the doses of those two products are the same so what you have to remember is in the weight loss trials those patients are being or participants are being

more closely monitored and are being encouraged to participate in lifestyle modifications so those dietary exercise programs and whatnot and just from that alone that addition alone that's why you see weight loss trials have such higher weight loss numbers than traditional diabetes trials because they're not focusing as much on the you know the lifestyle they're not as intensely monitoring the lifestyle um perspective so I think that really like goes a long way and is more of a long-winded way of saying like hey if you don't participate in the lifestyle stuff you're only gonna you're you're only

going to get as much as you put into it essentially right you get what you give yeah yeah another question I had Chris um when you're talking about the the oral uh weight loss agents you know you're seeing less less weight loss overall from those versus the injectables like like Zep bound like wovi is there um or do you think that the oral oral agents will become more powerful that it seems like that's a more palatable way of taking these rather than a once weekly injection um what do you think to the development of that

where you start to see more of those higher numbers in in an oral agent so that's that's interesting because that's obviously the the most um like you said palatable uh medication option the issue with those is that they're they're they're typically Limited in the fact that a lot of them work based on the fact that they simply have weight loss as a side effect because a lot of those medications that I listed Topiramate buproprion for example um those don't necessarily cause weight loss from a hormonal perspective and obviously when you're discussing hormonal um aspects the

hormonal aspect is obviously the stronger aspect um so I don't think that there are going to be significantly stronger oral traditional oral medications now I should hedge that by saying that there are um some oral glp1 agon in the pipeline which those May ultimately come to rival these injectable ones but again they're still working on the hormonal pathway so from a traditional oral medication standpoint I think we may have gotten we may have squeezed out all that we could have from what that you know from from that gotcha okay I would assume in terms of

any notable side effects that Zep bound would look a lot like wovi is this accurate are there any new safety concerns with Zep bound yeah yeah so that that's that's basically correct um because Zep bound works so similarly to wovi there were no new safety concerns identified um with the medic medication U generally speaking the most common adverse effects with all of the gp1 agonists and in the case of zound a dual ggp1 Agonist are are namely involving the GI tra so if you remember these medications work by slowing down the digestive system so abdominal

pain constipation decreased appetite diarrhea nausea and vomiting are all fairly common now these medic s have also been associated with rare cases of diabetic retinopathy gallbladder disease and pancreatitis and finally it's important to note that these medications should not be used in individuals with a personal or family history of certain types of tumors specifically medular thyroid carcinoma and multiple endocrine neoplasia syndrome type two but it's important to note that these are not new these were also aware in the med you know the medical community has been aware of all of these warning and precautions and

contraindications when using the diabetes forms of these medications which we've been using now for quite some time so the medical community is already quite aware of these things and shouldn't be too alarming um to hear with everything that we've mentioned about Zep bound it's its potency it's its efficacy are there any other notable areas to which it stands out from the other gp1 agonists the other weight loss agents on the market you know I just you know other than its Effectiveness in diabetes and weight loss not really I would I would say that it is

namely namely it is more potent so I guess that would just be you know where it stands out from the competition but you know from a cost perspective Zep bound May uh start to stand out given that it's actually uh it appears to be about $300 cheaper per month than either would go doie or saxenda but you know as with anything these things are always in flux and they can be subject to change based on Market pressur so can't gotta really take that with a grain of salt right and just for reference I did look

that up before uh before we talked the the cost of each the the list price zet bound is just a little over $1,000 $1,060 wovi is 1,349 and saxenda is also 1,349 so yeah that that bears out what you just said yeah yep Chris in our previous episode I asked you about the utilization of glp1 agonists in the corrections Health setting I was curious about that you said that you were seeing increasing usage and recommendation especially regarding diabetes treatment and the attendant cardiovascular benefits but as far as treatment for weight loss you said the uptake

was slow and that's to perhaps to be expected you noted you noted that cost PL a rooll as did the general tendency of weight loss drugs to be slowly integrated into the community at Large a year later have you seen any change specific to that at Weight Loss agents and of course now with a new option in the mix do you think that speeds the uptake H yeah so you know I haven't necessarily noticed a change in uptake in our main areas of focus those of course being Corrections and nursing home uh and I think

that makes sense with weight loss uh not often being the top priority in either of these patient populations plus with as you had mentioned cost uh being a huge concern um I think where the main increase will be seen you know at least right away is going to be in the community and unfortunately I can't really speak to that as much now that being said I don't think that utilization will increase simply because there is another option I think the utilization will increase because of the effectiveness of this new option as well as the attention

you know the media attention that has that has come with it um you know this is already pretty well known but but Z bound produc is results nearly to the extent seen with bariatric surgery um so we're starting to see these conversations you know from a pair perspective you know regarding the overall cost Effectiveness and overall quality of life of this therapy um versus existing surgical options and something that else that might drive the needle and and and may ultimately increase uptake in our areas of focus like Corrections and and nursing homes is there's actually

been new research coming out particularly with semaglutide um that s that shows that using we knew for years that use of semaglutide had cardiovascular benefits like you alluded to in the question in the diabetic population but we're now starting to see evidence uh of of cardiovascular benefits when using just for weight loss purposes as well which does make sense um given you know the cardiovascular risk that comes with you know obesity as well well so I think that as the community at large becomes more aware of the cardiovascular risk reduction both in diabetes or Standalone

obesity it's going to be harder to kind of deny those therapies to those patients because of the overall cost Effectiveness moving forward right you know as we record this Zep bound is supposed to be available in drug stores um what I read this morning end of 2023 but you had indicator me before we started recording that it is um showing up in with with wholesalers um so either way it's going to be available very soon um given the shortages that we saw and that we talked about with w wovi and OIC in particular do you

think it's a given that we we'll see that we'll see a shortage of Zep bound uh and just as a total side note the holiday season is an interesting time for a weight loss medication to officially hit the shelves given how people are so often preoccupied with weight gain around this time that's a side note but thought i' as as as with anything in the uh in the commercial or in the in the retail world you always want to come out right around Christmas time F you know St it's all about the stocking suffers Adam

so it couldn't be better timing um now although I don't think with the price tag as as Z found that it's necessarily a stocking suffer but that's neither here there um I you know honestly I don't I don't think and this is all just purely you know conjecture here but I don't think that we'll see shortages with Zep bound the way that we did with wi GOI and OIC and that's I think that's really because you know the shortages of OIC and wovi were sort of like the perfect storm um you know the manufacturer had

production issues that happened to occur at the same time as that social media hype boom that we saw um whereas Eli Lily you know which is the manufacturer of Mount jaro and zound they kind of have the advantage here in the fact that they're coming to market after both OIC and wovi so they've had the opportunity to kind of take a look look at that assess the market and they're kind they're likely going to be uh properly anticipating uh the market demand of their products at the risk of sounding totally trit here the these weight

loss medications they just keep getting better Chris are there any other agents in development that uh look to improve upon what wovi and Zep bound have started and I should rephrase that of course they're they're likely are there are but um are there any agents of development that are fairly close to coming out that look to improve upon what what wovi and upbound are doing yeah I mean you hit the nail on the head uh there's always things in development no matter what area of medicine you're looking at it's just that some are more robust

than others and this is a particular area that is is particularly robust and robust and you know I I'll kind of piggy back off of what you said because it's really impressive you know how they continue to seemingly create more and more effective options one after another um but like I said you know there are numerous agents in the pipeline right now that are being studied in fact there's a pair of um dual uh glp1 glucagon agonists so this is going to be a new class of medications uh compared to what is already available these

are uh pidu tide and cogu Tide uh they're being developed to actually induce weight loss and treat fatty liver disease which is you know a you know unique from what we've seen so far trials for these agents have demonstrated weight loss of 10% and 18% respectively um there is also a triagonist uh of glp1 Gip glucagon known as retach tide in development for weight loss uh specifically which has shown upwards of of 24% weight loss in clinical trial so we're talking slightly better if not you know comparable if not better than what we see with

Zep bound which is which is pretty wild additionally there's ongoing Research into oral agents that we alluded to earlier that also work on these hormonal Pathways with ororon and denlon both are as I mentioned oral glp1 agonists um they have thus far demonstrated potential weight loss of up to 15% um so slightly lower possibly than we go V and um and and Z bound but again you know like like we said before they may be the more palatable option because for the needle averse population and the good thing about these is they may also become

a prominent treatment for diabetes uh as well now I think what's most interesting about this particular space is that we've kind of gone from drugs that were exclusive to diabetes and then we've progressed into weight loss and we're now progressing even further into other metabolic diseases like fatty liver um in fact some of these agents like PM pidu tide have shown additional benefits with regard to blood pressure and cholesterol lowering so I think moving forward we're kind of going to have a situation where it won't necessarily be a one- siiz spits all but rather we're

going to have a full armamentarium of options that clinicians can choose from and going to be able to tailor to each individual patient which you know at the end of the day is really what good medicine is all about yes 100% And there's that Easter egg word again I heard I heard you drop it for your for your bingo cards all right uh just to end our conversation today I a few episodes back I spoke with your colleague in in Optics Henry so about bariatric surgery which you did talk about a little bit in this

episode we didn't get too heavy into the relationship between the new medications and and bariatric surgery but I wanted to get your perspective Chris what effect do you think that these drugs like like wovi like saxenda like Zep bound will'll have on bariatric surgery overall it could be easy for someone um obviously not in the medical field to just see what's what these drugs are doing and just generalize it wow you know they're just going to get better and eventually that surgery won't be necessary someday might there be any truth to that well I think

that in many cases pharmacological you know pharmacologic management will overtake bariatric surgery um at least in popularity given that it's less invasive and it produces fewer Downstream complications notably you know we see nutritional deficiencies um after you know many bariatric surgeries now that being said there will always be scenarios in which surgical measures reign supreme so for example um there are instances in which an individual may require more weight loss than a medication can provide I mean sure you know these medications are coming close to rivaling the weight loss seen with surgery uh particularly Zep

bound but at the end of the day surgery still does provide higher degrees of weight loss and another thing to consider is the durability of our medications to keep the weight off you know unfortunately these medications at a certain point they do kind of reach a plateau and individuals can actually start to out eat the medication and they start regaining some weight simply because their sense of hunger kind of comes back a little bit and additionally as with all medications of course these require patients to continue taking their medications on a on a regular basis

which regardless of whether it's you know a once daily or a once weekly no matter how easy or or simple the regimen becomes um it can still be difficult whereas with a surgery you know it's it's a oneand done type situation you get it and you're done so in settings of over of overcoming the medication and patients with non-adherence you know I think surgery is still going to you know likely be the preferred options now what's interesting to think about that I've even seen some experts discussing is there may even become situations where patients despite

having surgery may still have a small bit of weight left to lose and I think that's where we could even see the addition of medications on top of a surgery just for that patient to get that last little bit of weight loss that kind of push them over the line so in all I don't think this is going to be a situation of one truly overtaking the other but rather it may become a situation where the two can you know kind of be used in Synergy um or allow for a more stratified approach for weight

loss depending on various patient factors and as you said just a little bit earlier what good medicine is all about right exactly well so many exciting developments in the space that will no doubt continue to watch and quite possibly or I say likely discuss again Christopher Bender thank you so much for your time I hope you have a wonderful holiday season and I'm sure we'll talk again in the New Year well it's always a pleasure thank you for having me Adam have a happy holiday season and I look forward to talking about this again and

who knows maybe next year maybe in another year yeah for sure thanks Chris take care all right take take [Music] care podcast RX features conversations with with Healthcare professionals the statements and opinions discussed herein are for informational purposes only this podcast should not be considered professional medical advice and should not be used as a substitute for the advice of an appropriately qualified and licensed healthc care professional therefore listeners must not rely on the statements made here in but we do hope you enjoyed them podcast RX is a production of diamond Pharmacy Services the nation's largest

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