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Post by stevil on Apr 27, 2022 14:09:35 GMT -5
Unfortunately, the pump has borne out in the data to be the most effective treatment option. Again, until Afrezza goes head to head and proves superiority in high quality studies, nothing is going to significantly change.
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Post by stevil on Apr 27, 2022 7:59:31 GMT -5
I don’t think for the vast majority it’s a lack of empathy or interest in their patients. Many are burned out or just have rogue motivations. The vast majority are still well-meaning and compassionate. Of those, you’ll have some that don’t stay current in research.
Long story short, the biggest problem is a lack of data. The newer medications have so much information supporting their use, particularly in the later stages of the disease. Afrezza has none. If you’re going to have a paradigm shift, you cannot rely on old data for insulin but then say, “but this one is different”. Every claim in medicine needs to be supported, particularly when entering a crowded space full of several other well established options.
For Afrezza to really shine, in my opinion, it would be best for MNKD to show trials that early intensive insulin treatment can safely and effectively halt disease progression and prolong complications. That way you have a solo agent being used that physicians feel comfortable with. Plus, they’ll likely be using lower doses of units to remove the “fear factor “. I don’t think this latest dosing study will have much of an effect by itself. If anything, it’ll just be that much more intimidating when a doctor suggests doubling the dose- if you can even convince a doctor to recommend that to their patients. This is going to take a long time to adopt as habits and fears slowly erode over time. It’s a completely different way of approaching the disease. You’re flipping the long-standing protocol on its head. That isn’t going to happen easily or quickly. It will start with the data. No amount of knowledge will replace experience
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Post by stevil on Apr 25, 2022 17:49:58 GMT -5
Al got into a battle royale with Ralph Defronzo over how they just mask the problem. Is this interaction recorded anywhere?
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Post by stevil on Apr 3, 2022 12:45:26 GMT -5
You probably are eligible for this card. Your copay shouldn't be more than $15 per month. Off the top of my head, I thought this card had very generous benefits... basically it would cover full cost of the medication and lower it to $15 as long as it was covered by insurance. Some cards have deductibles that make you pay full price before it will kick in. I vaguely remember this card covering the full benefit and lowering copays to $15... Hope it helps! afrezza.com/savings-program/Ah, just found it. It covers up to $2000/month for 12 months. Actually, it looks like Wellcare is a medicare sponsored plan. Probably won't qualify for the card.
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Post by stevil on Mar 25, 2022 11:55:47 GMT -5
From Bill, “In recognizing the difficulty of changing from the status quo, and the need for data to justify that there is an implicit assumption that the status quo is good, we don’t want to change from “good” to “better” unless the data says so. This is prudent. But this is NOT the situation in diabetes. Current care is NOT GOOD. In that case when something seems like it might be better, even if one doesn’t have full-blown data to support it, it’s highly worth looking into. That’s my issue with diabetes and the treating doctors today. When you can’t get a patient’s A1c below 9 with all the various drugs and someone comes along making the case that you can get the person down to 6 safely, what have you got to lose?! An A1c of 9 will kill that patient. Try something?! For Gods sake!” I had no specific reason to post this here, there were two threads going on so I just picked a spot. More later…we are short on time:-) I agree with Bill wholly. The issue is with this comment, "When you can’t get a patient’s A1c below 9 with all the various drugs and someone comes along making the case that you can get the person down to 6 safely". Afrezza hasn't been shown to be able to do this yet. I agree that once it does, things will change. Unfortunately, unless I'm terrible at looking for this data, it doesn't exist in a respected and peer-reviewed journal- which is the kind of publication required to make changes in practicing habits. And to be fully clear and transparent, Bill has been gracious enough to agree to my request to teach me how to use Afrezza so that I can be able to do this myself. It's my hope that I'll be able to run my own small trial with my patients and submit it for publication at some point if the data is still lacking.
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Post by stevil on Mar 25, 2022 11:46:12 GMT -5
Do we really need more research? I would say yes, simply because I have tried to give lectures on the superiority of Afrezza and have found that it is more of a theoretical exercise than a proven one. There is a gross lack of convincing evidence for its use. The best they have is the STAT trial and that was with, what, a total of 20-something people? No one is going to change protocols based off of an n=20.
Also, again, I am in no way criticizing VDex. The more I learn about them (and Bill) the more I hold them in increasing regard. However, even if they get better results in their clinics, you'd still want to see Afrezza go head-to-head against other insulins and therapies. I believe I have seen it discussed here before, but one of the confounding factors of their success may be sample bias. It looks like VDex gives phenomenal personalized care to each of their patients. You would expect an improvement in quality metrics. It needs to be shown that it truly is Afrezza that is the cause of VDex's success, APART from that personalized care in order to sway opinions. You also have to consider the possible bias with clientele who seek care at a specialized treatment center. They are clearly concerned about their health and are motivated to change it. Unfortunately, this is not the norm in my experience with maybe up to half or more of those suffering from the disease. I agree with aged back when he/she said that people with diabetes don't want to think about their disease any more than they have to.
You could possibly make the case for Afrezza to be used as first line in the type of environment that offers close follow up and personalized care, but until it uses "real world examples" and has been proven to be more effective while maintaining safety (this will be the biggest boon to its success) it won't be changing anyone's minds. This is not meant to be critical of you or condescending in any way... I don't know how else to say it, so please forgive me. I don't think you realize how many assumptions you make regarding the safety and efficacy of Afrezza. I don't disagree with your assumptions but you have to realize that they are assumptions. Not everyone makes life/death decisions on assumptions, especially if they don't have to. I feel comfortable enough with what I know of Afrezza to prescribe it. I also understand why others may not feel that way and don't fault them for it. Hopefully MNKD has designed these new peds and India trials in a way that can showcase the true greatness of Afrezza.
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Post by stevil on Mar 25, 2022 9:50:23 GMT -5
Thanks for the kind words. I've put an awful lot of work into it so I'm glad it's paying off.
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Post by stevil on Mar 25, 2022 9:12:45 GMT -5
Stevil - you may be on to something here Maybe VDex needs to be working Indian Health Services to get changes made to their guide since they are doing so much work in New Mexico with native Americans. The AACE is an interesting organization - American Association of Clinical Endocrinology I went through their "Use of Advanced Technology in the Management of Persons With Diabetes Mellitus". It lays out a lot of the things we have been discussing such as extensive use of CGMs day 1. Things like Q2.4 When should diagnostic/professional continuous glucose monitoring be considered? - Newly diagnosed with diabetes mellitus - Persons with T2D treated with non-insulin therapies who would benefit from episodic use of CGM as an educational tool The Co-Chair who put this together is George Grunberger - former president of the AACE While the guide talks extensively about CGMs and their benefits there is not one mention of inhaled insulin or afrezza. The obvious question is did George never hear of afrezza? The answer is No. In fact George had worked with Mike Hoskins to get insurance authorization to use afrezza. Here is an oldy but goody www.ajmc.com/view/patients-report-barriers-to-getting-afrezza-but-a1c-results-are-worth-itIt also mentioned Saveth in addition to Hoskins. Five years later I wonder what happened to both? Maybe VDex needs to be working Indian Health Services to get changes made to their guide since they are doing so much work in New Mexico with native Americans. It will take these types of collaborations to fund the research necessary to sway expert opinion. This would be a huge undertaking, but it could certainly be beneficial for all parties involved. Historically, Native Americans have been one of the most difficult populations to treat, so I'm not sure I would want Afrezza to cut its teeth there... although if you have the confidence it'll work and want to make a splash, that's where you could do it. Plus, there would likely be adequate funding if you could convince the IHS it would be worthwhile. Just make sure you have the right providers that are up for the task. Very high provider burnout...
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Post by stevil on Mar 25, 2022 8:57:37 GMT -5
www.ncbi.nlm.nih.gov/pmc/articles/PMC8397556/pubmed.ncbi.nlm.nih.gov/32846935/pubmed.ncbi.nlm.nih.gov/28482281/These are just a few. There are better studies. A common "issue" I think I remember you citing was in regards to increasing the rates of amputation. This was only found with Invokana. Jardiance and Farxiga do not appear to have this risk. I have seen a couple patients go into DKA and develop Fournier's gangrene, but it is so rare that the benefit far outweighs the risk of these medications. I used to be very skeptical of this drug class when it first came out. I have seen so many patients have incredible success with them that I think it could displace metformin as SOC once it goes generic. This class of medicine appears to be a medical breakthrough due to all of the benefits it provides. As you'll see from the studies, it's being included in the SOC for CHF and CKD even without having DM2. Stevil, since when is spilling glucose into your urine a healthy sign? In general, you have a 12 year old coming in spilling glucose into their urine, what would the possible diagnosis be? Long term, it can not be good. try to think it through. Spilling glucose into urine stevil? In the past, spilling glucose into the urine was a pathophysiologic issue. It was not done intentionally. The reasons it happened before the SGLT-2is came out was because it overwhelmed the kidney's glomerulus's ability to filter glucose out of the blood... so it had no choice but to spill into the urine. The mechanism for SGLT-2is is different. It's actually showing to be beneficial for the kidneys. I asked a nephrologist about it and he said they don't really fully understand the mechanism yet but the theory behind its benefits is that it lowers intraglomerular pressure, thus preserving them longer. We've already seen this phenomenon with ace inhibitors and angiotensin receptor blockers- they produce the same effect through a different mechanism, but they have been a game changer in those with diabetes and chronic kidney disease. Their use has been validated over and over throughout time as patients have had delayed progression in CKD while using those medications. So to answer your question, it is not good, but it's better than the alternative. Spilling glucose into the urine has many different effects- like dehydration because of the osmotic effect of glucose and water which can lead to DKA. Bacteria and fungus love sugar- it will increase rates of infection in the bladder/kidneys and the surrounding areas of the urethra. In medicine we measure all of our decisions through risk/reward analysis. There is a higher risk of bad things happening with taking this medication. However, the reward you get from it- ie. better glucose control, cardiorenal protection, etc... all of those are more beneficial than the complications associated with the medications. Doing nothing is more dangerous than taking the medication. We have numerous studies showing this to be true.
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Post by stevil on Mar 24, 2022 14:33:03 GMT -5
In the age of CGMs why wouldn’t the SoC recommend all newly diagnosed T2s get at least a 2 week AGP but probably 6 months? We have diet companies like Levels and Nutrisense pushing CGM’s for diet control. Why do CGM's require a prescription? They don't in the EU. Why is the ADA the only diabetes organization publishing a doctor’s diabetic guide for care? Does it have to be? It doesn’t seem the ADA has any competition and I don’t think the SoC is very good. That SoC card is just so convoluted and IMO could be simplified by adding CGMs and afrezza. I don't even see CGMs mentioned. Here is a picture pbs.twimg.com/media/Du4s6lMWwAEqm5r.jpg:largeWho gave the ADA this power? It seems to me its time for a new organization publishing a new doctor’s guide promoting the early use of CGM’s and afrezza. Maybe Dave Kendall’s approach of working with the ADA to change the SoC after getting stonewalled was the wrong approach. Maybe Dave should have started a new association. Does the ADA have any competition with a doctor's guide? What if they did? It sure would be nice to hand out a simple card during Mike's "Seeing is Believing" campaign to have a simple prescribing guide which highlights the CGM and afrezza use to hand out to the GPs. Why do CGM's require a prescription? This one makes sense to me but only in the context of insurance coverage. Patient's who want to purchase their own outside of their insurance should not be restricted. Must be a liability issue in case they develop infection? Maybe they need someone to show them how to install it? Why is the ADA the only diabetes organization publishing a doctor’s diabetic guide for care? They're not. There are several. Here are just a few others. pro.aace.com/disease-state-resources/diabetes/clinical-practice-guidelines-treatment-algorithms/new-2021www.ihs.gov/diabetes/clinician-resources/dm-treatment-algorithms/www.dshs.texas.gov/txdiabetes/toolkit/Treatment-Algorithms,-Protocols,-Guidelines-and-Recommendations/ Who gave the ADA this power? I'm not sure what power you're talking about. Their guidelines are respected because they have some of the most resources available to compile and analyze data and they have the thought leaders in the field working for them. Even though I don't necessarily agree with their algorithm, I do think it is a good "guideline" when you're not sure how to approach a patient that is new to you. It's a very easy to follow and mostly effective plan. Remember, just because diabetes is worsening, doesn't mean treatment is worsening. Treatment is improving, it's just that the habits that are causing the underlying disease is worsening. The medications we have now are far better than we used to have. It's just the causes of the disease are getting so much worse that the treatments aren't able to keep up. Afrezza might be able to fix this issue, but it remains to be seen that even when given the best tool that people will be compliant with at least 3 puffs a day. In other words, it's not always the treatment that's the issue and a treatment can only be effective if it's used properly. Maybe Dave should have started a new association. What evidence do you think he would be able to present at this new association to garner respect from his colleagues and peers?
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Post by stevil on Mar 24, 2022 13:56:16 GMT -5
Not me. I'm trying to save a few minutes with the family.
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Post by stevil on Mar 24, 2022 12:31:40 GMT -5
Is the ADA the only gatekeeper? If step 1 of the SoC was to give the new PWD a CGM and based on their AGP results step 2 would be to add afrezza, would that change how doctor's prescribed afrezza? Would that force insurance to cover it? Would this change reduce PWD complications from developing? Does the SoC not only dictate what the doctor should prescribe but if insurance will cover it? In the age of CGMs why wouldn’t the SoC recommend all newly diagnosed T2s get at least a 2 week AGP but probably 6 months? We have diet companies like Levels and Nutrisense pushing CGM’s for diet control. Why do CGM's require a prescription? They don't in the EU. Why is the ADA the only diabetes organization publishing a doctor’s diabetic guide for care? Does it have to be? It doesn’t seem the ADA has any competition and I don’t think the SoC is very good. That SoC card is just so convoluted and IMO could be simplified by adding CGMs and afrezza. I don't even see CGMs mentioned. Here is a picture pbs.twimg.com/media/Du4s6lMWwAEqm5r.jpg:largeWho gave the ADA this power? It seems to me its time for a new organization publishing a new doctor’s guide promoting the early use of CGM’s and afrezza. Maybe Dave Kendall’s approach of working with the ADA to change the SoC after getting stonewalled was the wrong approach. Maybe Dave should have started a new association. Does the ADA have any competition with a doctor's guide? What if they did? It sure would be nice to hand out a simple card during Mike's "Seeing is Believing" campaign to have a simple prescribing guide which highlights the CGM and afrezza use to hand out to the GPs. Is the ADA the only gatekeeper? No, but they do have a lot of influence. See below. If step 1 of the SoC was to give the new PWD a CGM and based on their AGP results step 2 would be to add afrezza, would that change how doctor's prescribed afrezza? Most likely Would that force insurance to cover it? I actually don't know this for sure, but I don't think insurance companies are forced to cover anything. I believe they choose to have more generous offerings due to the free market. Meaning if their plan sucks at covering medications, people won't want to pay for it. Someone can correct me if I'm wrong. Would this change reduce PWD complications from developing? Only way to know for sure is to have retrospective studies evaluating complications and outcomes of those on Afrezza vs SOC. Does the SoC not only dictate what the doctor should prescribe but if insurance will cover it? There is a bit of nuance to this question. You have variation in medicine depending on both doctors and physicians. As a general rule, most doctors (evidence-based, anyway) prescribe and insurance companies cover the SOC. It is far more the rule than the exception. However, some physicians deviate from "guidelines" because they are don't see their patients as a whole of a population the SOC is based on but as an individual who may have needs different than "normal". You also have less restrictive insurance companies that are more generous in their benefits... if you're able to afford them. You get what you pay for. Why wouldn’t the SoC recommend all newly diagnosed T2s get at least a 2 week AGP? Most often, it's not necessary. Unless someone avoids their doctors like the plague, they'll usually seek medical advice when they start noticing they're peeing 2-3 times an hour and can't satiate their thirst. People usually get caught early enough that they don't need to be put on insulin right away, at least according to current "guidelines". For those that do get caught with severe disease, they do get started on insulin right away, and, in theory, you could prescribe them a CGM, but generally anyone that goes on insulin gets prescribed a glucometer and test strips and is told to test as much or as little as they're willing to. I'll respond to others as I have time... Gotta run.
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Post by stevil on Mar 24, 2022 10:24:20 GMT -5
I would say we are in violent agreement on that. By the time they are in the wheel chair its too late but could they have avoided the wheel chair? So how do we get the new DM on afrezza first and not last? Is it really all about the SoC? Is the ADA the only gatekeeper. If step 1 on the SoC was gave the new PWD a CGM and take a walk based on their AGP results add afrezza as needed, would that force insurance to cover it? Does the SoC not only dictate what the doctor should prescribe but if insurance will cover it? Who gave the ADA this power? Do they have any competition? What if they did? What if Dave Kendall started his own association and his own SoC when the ADA stonewalled him? As far as GLP1s generating beta cells I am very familiar with Ralph Defronzo's work. I would also bet my last dollar that afrezza will do a better job at stopping and in somes case reverse progression - promote beta cell generation than GLP1s. Unfortunately this is not likely to happen under our current healthcare system. Politics aside, it would likely take some form of universal healthcare to make Afrezza first because the cost of therapy is so much higher than metformin. Of course it would first require that Afrezza be shown to even be cost-effective in lowering total healthcare bills. That will take many years and far more patients to bear out. There has to first be evidence that Afrezza will lower the cost of hospitalizations, complications, and overall cost of diabetes complications before anything can start. Then, and only then, will insurance companies start to pay attention. They're not in the business of health, they're in the business of making money providing coverage for healthcare. Their motivation isn't outcomes per say, rather how cheaply they can have beneficial outcomes. Right now, I would say Afrezza's biggest hope is Medicare. If they are able to reduce hospitalizations, arterial bypass in the heart or peripheral extremities, strokes, etc, then just maybe it will become first line INSULIN. Medicare tends to set the precedent that other insurance companies follow. I think it will still be a hard sell as first line treatment, simply because not all people develop complications from diabetes. There is a lot to still learn about diabetes- certainly more than I know- it's not a one-size-fits-all disease. There will have to be a threshold somewhere for Afrezza's use because unless it is as cheap as metformin (which will be never), it won't really be cost-effective. Maybe in the future they will have it dialed in by who is higher risk of progression and complications depending on genetic factors, receptors, levels of insulin resistance, etc. I have great admiration for Bill and VDex and I don't even really disagree with his premise, it's just a pipe dream that Afrezza will ever be first line therapy for everyone with diabetes because, for some, it would be like using a sledgehammer to kill an ant. I don't think the ADA has as much power as this board seems to think. Absolute power corrupts absolutely- I believe this and I do think there is corruption in any industry where there is a lot of money to be made. Having said that, the problem right now isn't that the ADA is blocking Afrezza, at least I don't believe this to be the case. The ADA is an evidence-based organization that has to have evidence for their decisions and recommendations. Just as they cannot give recommendations with a lack of evidence, they cannot give recommendations against compelling evidence. As of now, there is no compelling evidence for Afrezza. All the evidence that exists is largely anecdotal or has been done by VDex in their white papers. While those papers are well-written and fundamentally sound, that is not enough to make or change current guidelines. Way more evidence is needed and needs to be peer-reviewed before it will be taken seriously. I'm not saying that Bill or VDex is dishonest, greedy, or conflicted at all in their mission. However, think of it this way. Do you want your doctor to make their medical decisions based off of a company that has openly stated that they are current shareholders in the company they are trying to promote? It doesn't nullify their data, but it sure could be a conflict of interest. You'd want to see other people without those conflicts coming up with the same results, and on a broader scale. That hasn't happened yet. Until it does, I'll reserve throwing my stones at the ADA. As far as the GLP-1s go... they have proven themselves in the data. Afrezza has not at this point in time. That you have to make a bet lends proof to this argument. It's not an illogical conclusion, it's just one that hasn't been justified yet. And you don't skip steps in medicine. It is an inherently conservative and slow-moving field, for better or for worse. I would contend more often better than worse. If MNKD conducted their trials correctly early on, Afrezza would likely be in a much different situation. This is why it's so difficult for small companies to do well in this field. It takes an enormous amount of money to prove medications are excellent. And for every success there are a number of failures that need to also be financially offset.
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Post by stevil on Mar 24, 2022 9:05:42 GMT -5
A very common misconception on this board is that Afrezza will cure all things diabetes. While it may prove to ameliorate much of the disease process, it's not as simple as saying "take Afrezza and you'll have perfect health again". I will gladly eat my words if I am proven wrong in the future, however, diabetes is not just a blood sugar issue. It is usually a metabolic issue with so many additional complex processes going haywire. What if I told you that there studies that showed no benefit of lowering A1c below 7 for morbidity/mortality? pubmed.ncbi.nlm.nih.gov/21791495/And let's please not get into the debate about whether A1c is a good tool for measuring glucose control because we're on the same team that TIR is far superior. The point remains, TIR is only relevant in preventing destruction from disease. Once it has already occurred, it becomes far less relevant. Diabetes is not just an insulin issue in many cases. It's just one component of the larger disease. I can certainly see HOW/WHY Afrezza could be the solution, but the truth is, it has not yet been borne out in the details. Quite the opposite, actually, and until Afrezza proves incorrect what we already know to be true, the onus and burden of proof is on Afrezza. Much of the reason (my opinion) Afrezza will have trouble with adoption if it remains such an expensive option is that glucose control is one component of many that need to be addressed. Keep in mind my career is still young, but it is very rare that a patient has difficulty controlling their blood sugar if they eat properly and exercise. I can't tell you how many patients I have cared for with A1cs less than 8 on orals alone and the great majority are less than 7. But DM2 isn't their problem. The underlying issue is poor dietary choices, poor exercise, other comorbid conditions that limit their ability to exercise because they have been obese for so long that they have developed osteoarthritis. People also forget that DM2 has direct correlation with age. The older people get, the harder it is to exercise due to less energy, aches/pains/stiffness. Afrezza will help reduce complications from their diabetes, but it'll forever be just a bandaid for the true underlying issues. Later in the disease process you start to have irreversible complications like CKD, CHF, neuropathy, PVD, gastroparesis, etc. Afrezza will not fix any of those, of that I am completely certain. Afrezza will have its greatest benefit in pediatric patients and newer-ish diagnosed DM patients who have not yet developed complications from the disease. It will be far more effective in preventing comorbid conditions than any other medication. But there remains a necessity for all the other cascade effects of the metabolic syndrome that is diabetes. That's where SGLT-2is and maybe even GLP-1s come in. GLP-1s have been showing to be able to regenerate beta cells in the pancreas. I don't think Afrezza will have the same result. If you give Afrezza to someone in a rolling walker/chair who cannot walk due to class 3/4 CHF, you'll have better glucose control in someone who can't walk and is wheelchair bound. Their life expectancy really doesn't change much at that point. If you give that same person an SGLT-2, they might be able to walk a few more steps before needing their rolling walker/chair. I am extremely pro-Afrezza and have been on the board long enough to have a feel for the general medical understanding of the benefits of Afrezza that the common board member has. I think Afrezza gets lifted a little too high onto a pedestal. I am certain it has the potential to revolutionize the diabetes industry. However, I don't think it will ever obviate the need for other medications or therapies- At least not until it is the absolute first line and given early in the disease to prevent the development of other comorbidities. Once those other conditions set in, though, it should not be used alone. JMO. Edit: I painted the disease with a very broad stroke. Not all people with diabetes (type 2) are obese or have poor diet and exercise habits. But I would say the vast majority. For those who do everything right and still struggle with glucose control, it truly is unfortunate. And that, probably more than anything, is why I want to learn how to use Afrezza properly.
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Post by stevil on Mar 24, 2022 8:12:54 GMT -5
I can't answer your question on the FDA. Why does the FDA approve SGLT2s which cause all kinds of issues? Why does the FDA require a black box on afrezza for a condition which is so rare I don't think it has happened since afrezza was approved? www.ncbi.nlm.nih.gov/pmc/articles/PMC8397556/pubmed.ncbi.nlm.nih.gov/32846935/pubmed.ncbi.nlm.nih.gov/28482281/These are just a few. There are better studies. A common "issue" I think I remember you citing was in regards to increasing the rates of amputation. This was only found with Invokana. Jardiance and Farxiga do not appear to have this risk. I have seen a couple patients go into DKA and develop Fournier's gangrene, but it is so rare that the benefit far outweighs the risk of these medications. I used to be very skeptical of this drug class when it first came out. I have seen so many patients have incredible success with them that I think it could displace metformin as SOC once it goes generic. This class of medicine appears to be a medical breakthrough due to all of the benefits it provides. As you'll see from the studies, it's being included in the SOC for CHF and CKD even without having DM2.
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