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Post by peppy on Jul 15, 2018 11:51:03 GMT -5
Trulicity..... My friends client was having all the same horrible side effects;( 60-year-old type2.) I asked if she was on Metformin? My friend did not know. This whole story took weeks to play out...the client thought she was dying, the doctor didn’t know what was wrong with her, she got tested for all kinds of things and finally SHE figures out what’s wrong. Trulicity! She will be changing doctors next month and going to a Afrezza friendly doctor in Temecula, so we’ll see what happens:-) She is not my client so I do not have direct contact with her. Of course it was recommended by her doctor she didn’t even know what it was. perhaps a bit off topic. endogenous GLP-1 is rapidly degraded primarily by dipeptidyl peptidase-4 (DPP-4), but also neutral endopeptidase 24.11 (NEP 24.11) and renal clearance, resulting in a half-life of approximately 2 minutes. Consequently, only 10–15 % of GLP-1 reaches circulation intact, leading to fasting plasma levels of only 0–15 pmol/L. To overcome this, GLP-1 receptor agonists and DPP-4 inhibitors have been developed to increase GLP-1 activity. en.wikipedia.org/wiki/Glucagon-like_peptide-1
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Post by agedhippie on Jul 15, 2018 16:09:50 GMT -5
Aged - I think this may be a first so let me make sure I am reading this correctly - Are you now saying Dr. Kendall has a significant chance of getting afrezza to replace the RAA's in the standard of care in a couple of years? When are you going to give it a try now that you see it moving in the direction of being the standard of care? What I remember coming out of ADA2018 was the analysis of Affinity-1(171) in conjunction with the STAT Pilot findings that current T1s using an RAA could reduce A1c from 8.0 to 6.8 with no additional hypoglycemia which is WAY BEYOND non-inferior. That I would call is GAME CHANGING. When you say "Even STAT has Afrezza as inferior to RAA for TIR unless you take two doses per meal" is clearly incorrect at the 1hr mark. The RAAs are not even close. As Dr. Kendall works through his dosing two things will happen; basal levels will be increased; and meal time initial dose will also be increased. Both will increase TIR at the 2hr mark without the second puff. Lets see what he comes out with but this I believe is where he is headed with the T1s. For the T2s its easy, afrezza first, afrezza only and go big on the dose with no worries. Concerning Trulicity, people take what their doctors prescribe. Ask a PWD why they are taking a certain medication and the answer is usually "my doctor said to". Its blind faith their doctor knows what they are doing. How many people took Orinase, or Actos or the others? How many people did Actos kill in the Accord study? If its in the standard of care and their sales guy buddy is pushing it, the doctors prescribe. As history has demonstrated the patient ends up being the victim with serious heart damage, liver, kidney and pancreatic cancer or a missing toe or foot. As far as afrezza and the AP, I think what current studies have clearly demonstrated afrezza makes TIR better for the AP but raises the question "is a simple patch pump just as good when you have afrezza". Maybe I should phrase that better. I don't think it is possible to replace RAA in the SoC in less than two years. The reason is that it will take a large scale trial to prove superiority and I think it is unlikely you can get that done in less than two years. Remember that for the 171 trial the hypo results were not statistically significant. Mannkind even had to correct their press release to acknowledge that. Yes there were less hypos in that ranges, however there were also ranges where there more hypos as I remember (look at the higher A1c groups). The issue is that the absolute numbers were small. I am not quite sure what you mean by TIR, but TIR is over a 24 hour period and not just immediate post-prandial. Even Mannkind's own slides show that Afrezza TIR was inferior to RAA unless a follow up dose was used. Personally I don't like GLP-1 and would rather people used insulin. However doctors seem to love it as evidenced by Trulicity's sales figures. As to SGLT-2 - amputation does not seem to be a class effect as the FDA does not see the same problem with Jardiance or Farxiga, just with Invokana. SGLT-2 reduces the risk of heart failure significantly. Ultimately the running costs of a patch pump are not significantly less than a regular pump. Look at Omnipod which is a simple patch pump (no intelligence beyond a bolus wizard and even my meter does that!) The pump battle was over once Medtronics said they would let insurers pay by results. Aetna is all over this. I called them to see if it was real and they wanted to get me signed up there and then which never happens with an insurer normally.
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Post by agedhippie on Jul 15, 2018 16:15:26 GMT -5
Let’s say this again:-)) When you say "Even STAT has Afrezza as inferior to RAA for TIR unless you take two doses per meal" is clearly incorrect at the 1hr mark. The RAAs are not even close. As Dr. Kendall works through his dosing two things will happen; basal levels will be increased; and meal time initial dose will also be increased. Both will increase TIR at the 2hr mark without the second puff. Lets see what he comes out with but this I believe is where he is headed with the T1s. For the T2s its easy, afrezza first, afrezza only and go big on the dose with no worries. Read more: mnkd.proboards.com/thread/10219/8k-filing?page=5#ixzz5LLI6X0DhI absolutely do not dispute that. At the 1 hour mark Afrezza is very clearly superior using any dosing regime, but TIR is measured for 24 hours because it is a proxy for control. Better TIR should equal less damage so a good or bad TIR for an hour should not be significant in the long run.
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Post by brotherm1 on Jul 15, 2018 18:06:36 GMT -5
Let’s say this again:-)) When you say "Even STAT has Afrezza as inferior to RAA for TIR unless you take two doses per meal" is clearly incorrect at the 1hr mark. The RAAs are not even close. As Dr. Kendall works through his dosing two things will happen; basal levels will be increased; and meal time initial dose will also be increased. Both will increase TIR at the 2hr mark without the second puff. Lets see what he comes out with but this I believe is where he is headed with the T1s. For the T2s its easy, afrezza first, afrezza only and go big on the dose with no worries. Read more: mnkd.proboards.com/thread/10219/8k-filing?page=5#ixzz5LLI6X0DhI absolutely do not dispute that. At the 1 hour mark Afrezza is very clearly superior using any dosing regime, but TIR is measured for 24 hours because it is a proxy for control. Better TIR should equal less damage so a good or bad TIR for an hour should not be significant in the long run. Oh come on Hipster, do we need to swear you in before you start yappin? How about telling the WHOLE truth? Just for starters - before I let Sayhey step in and tear you a new one - who only eats one meal per day as your post implies? 🙂
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Post by mannmade on Jul 15, 2018 18:29:14 GMT -5
And what is wrong with taking a second or even third bolus with AFREZZA to keep a tight TIR and as a result reduced Hba1c? With RAA’s this is difficult because of stacking and very likely “roller coaster “ effect or worse a hypo event and hospital ER visit. Isn’t the point of AFREZZA’s fast in and fast out that here is less issue with stacking and therefore less severe hypos which implies you would take a second or even third bolus sometimes pending what you eat.
If I were diabetic I would gladly use a cgm and sugar surf to maintain a tight TIR. I have my phone with me all the time anyway.
With no disrespect to anyone I am not sure why this is so complicated to understand. It seems the very benefit of AFREZZA of fast in/fast out is being used against it by some as a negative. Dosing is different and that is the point as I understand it.
I thought the whole point was RAA’s are very complicated to use w carb counting etc and AFREZZA seems (to me at least) so much easier to use. Less work, less complications and better results.
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Post by peppy on Jul 15, 2018 18:37:34 GMT -5
And what is wrong with taking a second or even third bolus with AFREZZA to keep a tight TIR and as a result reduced Hba1c? With RAA’s this is difficult because of stacking and very likely “roller coaster “ effect or worse a hypo event and hospital ER visit. Isn’t the point of AFREZZA’s fast in and fast out that here is less issue with stacking and therefore less severe hypos which implies you would take a second or even third bolus sometimes pending what you eat. If I were diabetic I would gladly use a cgm and sugar surf to maintain a tight TIR. I have my phone with me all the time anyway. With no disrespect to anyone I am not sure why this is so complicated to understand. It seems the very benefit of AFREZZA of fast in/fast out is being used against it by some as a negative. Dosing is different and that is the point as I understand it. I thought the whole point was RAA’s are very complicated to use w carb counting etc and AFREZZA seems (to me at least) so much easier to use. Less work, less complications and better results. Molly always gave herself the same dose. Carb counting my assets. I agree with mannmade. Additionally the afrezza dosing thingy is still being worked on. ADD1 Afrezza dynamic dosing study. Dosing RAA's much more difficult.
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Post by sayhey24 on Jul 15, 2018 19:18:28 GMT -5
Aged - I am not sure where you are getting "TIR is measured for 24 hours because it is a proxy for control". TIR is measured through out the 24 hr period. Are in in/out at 9am, at noon, at 6pm, etc. or at every hour mark or 30 minutes or second of the day. What was not possible prior to CGMs is now very doable to measure.
If you look at the STAT results afrezza kicked ass during the two hour period after meals which is the goal of a prandial. After 2 hours its back to the basal for the T1 or the pancreas for the T2.
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Post by agedhippie on Jul 15, 2018 20:52:17 GMT -5
Aged - I am not sure where you are getting "TIR is measured for 24 hours because it is a proxy for control". TIR is measured through out the 24 hr period. Are in in/out at 9am, at noon, at 6pm, etc. or at every hour mark or 30 minutes or second of the day. What was not possible prior to CGMs is now very doable to measure. If you look at the STAT results afrezza kicked ass during the two hour period after meals which is the goal of a prandial. After 2 hours its back to the basal for the T1 or the pancreas for the T2. TIR is the percentage of time you are in the range 180 - 70 range over a 24 hour period. Optionally you can add the standard deviation as well. Look at slide 69 - the people taking Afrezza once per meal averaged about 48% of the day in range. The people on RAA averaged about 55% of the day in range. The people taking Afrezza twice per meal averaged about 62% of the day in range. As a comparison the Medtronics 670G pump trial averaged 72% of the day in range (and that was a big trial). As to performance; the twice per meal dosing was the hands down winner over the four hour window, the once per meal Afrezza dose out-performed RAA for about 1.5 hours and under-performed for 2.5 hours. (Slide 66)
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Post by agedhippie on Jul 15, 2018 21:08:14 GMT -5
And what is wrong with taking a second or even third bolus with AFREZZA to keep a tight TIR and as a result reduced Hba1c? With RAA’s this is difficult because of stacking and very likely “roller coaster “ effect or worse a hypo event and hospital ER visit. Isn’t the point of AFREZZA’s fast in and fast out that here is less issue with stacking and therefore less severe hypos which implies you would take a second or even third bolus sometimes pending what you eat. If I were diabetic I would gladly use a cgm and sugar surf to maintain a tight TIR. I have my phone with me all the time anyway. With no disrespect to anyone I am not sure why this is so complicated to understand. It seems the very benefit of AFREZZA of fast in/fast out is being used against it by some as a negative. Dosing is different and that is the point as I understand it. I thought the whole point was RAA’s are very complicated to use w carb counting etc and AFREZZA seems (to me at least) so much easier to use. Less work, less complications and better results. This is actually a very good question. The typical scenario is that you bolus at the meal, and then get on with your day until the next meal. People tend not to do multiple boluses because it interferes with their lifestyle. Obviously if your blood sugar goes completely out of control you don't wait for the next meal. With MDI you are told to test and correct at the two hour mark, but it is fairly rare to find people who actually do that although some do. This becomes a compliance issue as you saw with STAT - that non-compliant group was not part of the design. With more time I would be willing to bet the non-compliant group would grow. Contrary to what people seem to think stacking insulin is not a quick way to ER. People routinely stack insulin, pumps and some meters will even manage it for you. You still have to carb count with Afrezza if you are Type 1 as their own trial showed, but you can be less accurate which is a benefit. However is I take an 8u cartridge for a 4u meal I absolutely will have a hypo as the trial showed. Don't take my word for it, look at Dr Edelstein. He takes Afrezza for fast carbs and corrections, for meals he uses his pump.
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Post by peppy on Jul 15, 2018 21:12:25 GMT -5
And what is wrong with taking a second or even third bolus with AFREZZA to keep a tight TIR and as a result reduced Hba1c? With RAA’s this is difficult because of stacking and very likely “roller coaster “ effect or worse a hypo event and hospital ER visit. Isn’t the point of AFREZZA’s fast in and fast out that here is less issue with stacking and therefore less severe hypos which implies you would take a second or even third bolus sometimes pending what you eat. If I were diabetic I would gladly use a cgm and sugar surf to maintain a tight TIR. I have my phone with me all the time anyway. With no disrespect to anyone I am not sure why this is so complicated to understand. It seems the very benefit of AFREZZA of fast in/fast out is being used against it by some as a negative. Dosing is different and that is the point as I understand it. I thought the whole point was RAA’s are very complicated to use w carb counting etc and AFREZZA seems (to me at least) so much easier to use. Less work, less complications and better results. This is actually a very good question. The typical scenario is that you bolus at the meal, and then get on with your day until the next meal. People tend not to do multiple boluses because it interferes with their lifestyle. Obviously if your blood sugar goes completely out of control you don't wait for the next meal. With MDI you are told to test and correct at the two hour mark, but it is fairly rare to find people who actually do that although some do. This becomes a compliance issue as you saw with STAT - that non-compliant group was not part of the design. With more time I would be willing to bet the non-compliant group would grow. Contrary to what people seem to think stacking insulin is not a quick way to ER. People routinely stack insulin, pumps and some meters will even manage it for you. You still have to carb count with Afrezza if you are Type 1 as their own trial showed, but you can be less accurate which is a benefit. However is I take an 8u cartridge for a 4u meal I absolutely will have a hypo as the trial showed. Don't take my word for it, look at Dr Edelstein. He takes Afrezza for fast carbs and corrections, for meals he uses his pump. wow, you saw all that in two charts and a couple of paragraphs? We have yet to see/read the study and the dosages. Was Dr Kendall's presentation taped? Aged, remember when you thought vdex wouldn't be able to handle diabetics?
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Post by agedhippie on Jul 15, 2018 21:18:26 GMT -5
Molly always gave herself the same dose. Carb counting my assets. I agree with mannmade. Additionally the afrezza dosing thingy is still being worked on. ADD1 Afrezza dynamic dosing study. Dosing RAA's much more difficult. That is how they used to tell you to take insulin pre-MDI. It was horrible and people had truly awful numbers. Sadly some people still this, I met a Type 1 in a cafe the other day who was doing just that and we started chatting. I suggested that they might consider varying the dose with food and they had no interest at all in changing - they thought it was to much bother and easier to just always take the same dose. Needless to say their HbA1c was horrific. I don't push though because everyone has their way of coping and as long as they understand the consequences (and most Type 1s seem to) then it's their life to live.
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Post by agedhippie on Jul 15, 2018 21:22:29 GMT -5
wow, you saw all that in two charts and a couple of paragraphs? We have yet to see/read the study and the dosages. Was Dr Kendall's presentation taped? Aged, remember when you thought vdex wouldn't be able to handle diabetics? I tend to read slide decks very closely, it's a side effect of my job! I am definitely looking forward to seeing the data from STAT. Is the webcast on Mannkind's investor site? Obviously I was (and not for the first time) completely wrong. VDEX are doing a sterling job with diabetics.
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Post by peppy on Jul 15, 2018 21:30:11 GMT -5
wow, you saw all that in two charts and a couple of paragraphs? We have yet to see/read the study and the dosages. Was Dr Kendall's presentation taped? Aged, remember when you thought vdex wouldn't be able to handle diabetics? I tend to read slide decks very closely, it's a side effect of my job! I am definitely looking forward to seeing the data from STAT. Is the webcast on Mannkind's investor site? Obviously I was (and not for the first time) completely wrong. VDEX are doing a sterling job with diabetics. quote: I tend to read slide decks very closely, it's a side effect of my job! reply: I tend to look at charts closely also. I am sure you haven't missed that fact.
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Post by agedhippie on Jul 15, 2018 21:30:25 GMT -5
I absolutely do not dispute that. At the 1 hour mark Afrezza is very clearly superior using any dosing regime, but TIR is measured for 24 hours because it is a proxy for control. Better TIR should equal less damage so a good or bad TIR for an hour should not be significant in the long run. Oh come on Hipster, do we need to swear you in before you start yappin? How about telling the WHOLE truth? Just for starters - before I let Sayhey step in and tear you a new one - who only eats one meal per day as your post implies? 🙂 Yeah, I could have phrased that better. Looking at the 4 hour charts for a meal in the slide deck (slides 64 to 66) Afrezza is always superior at the 1 hour mark. However TIR is measured over a 24 hour period so you have to consider what happens in-between the 4 hour windows as well.
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Post by sayhey24 on Jul 16, 2018 5:34:50 GMT -5
Aged - when we are talking afrezza we don't care about 24 TIR. We care about the 12 hr TIR basically 8am to 8pm which are the working hours of afrezza. Assuming 6pm dinner afrezza's job is done by 8pm. At that point you have the night shift and that work is done by the basal. To address TIR during the 3rd shift requires a basal adjustment and has nothing to do with afrezza.
Prior to afrezza I understand it was not possible to split the day into waking and sleeping hours but afrezza shifts the paradigm. Because of the long RAA tail I understand your 24 hr stance but afrezza has obsoleted this. I know it does not make the numbers "fair" for the RAAs but too bad so sad.
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