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Post by mango on Jun 6, 2018 12:02:59 GMT -5
Aged, I am glad you finally admitted— Aspart had a lower HbA1c because it caused more hypos.
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Post by mnholdem on Jun 6, 2018 13:02:11 GMT -5
Jeez, you guys are on a roll today!
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Post by wsulylecoug on Jun 6, 2018 13:23:54 GMT -5
This thread is great in that it shows how well educated many PB posters are with their abilities to dissect and discuss past studies and more. Now consider that Dr. Kendall, the former Chief Scientific Medical Officer for the ADA, has already done the same in much, much greater depth and concluded that the studies contain "veins of gold" and that Afrezza should be the standard of care. Mike too has said, "doctor's are shocked" when they hear the results. I'm hopeful the company's strategic plan is to bring clarity to these statements in a big way at the ADA and this will truly explode the scientific chatter that is the topic of this thread. If this chatter is paired with a new marketing push, it could be the game changer and paradigm shift we've waited over 10 years to see. IMO, I can't see how this is not going to happen. GL I don't think any amount of chattering here on proboards is going to impact scripts. Doctors are unlikely to see it, and they want cold hard trial results not poetic phrases. Maybe he meant the chatter that is going on outside of this thread, like the information that is provided in the blog, quotes and such by others, and not necessarily this thread in particular?
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Post by mango on Jun 6, 2018 13:25:25 GMT -5
This thread is great in that it shows how well educated many PB posters are with their abilities to dissect and discuss past studies and more. Now consider that Dr. Kendall, the former Chief Scientific Medical Officer for the ADA, has already done the same in much, much greater depth and concluded that the studies contain "veins of gold" and that Afrezza should be the standard of care. Mike too has said, "doctor's are shocked" when they hear the results. I'm hopeful the company's strategic plan is to bring clarity to these statements in a big way at the ADA and this will truly explode the scientific chatter that is the topic of this thread. If this chatter is paired with a new marketing push, it could be the game changer and paradigm shift we've waited over 10 years to see. IMO, I can't see how this is not going to happen. GL I don't think any amount of chattering here on proboards is going to impact scripts. Doctors are unlikely to see it, and they want cold hard trial results not poetic phrases. Veins of Gold
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Post by peppy on Jun 6, 2018 13:34:14 GMT -5
This thread is great in that it shows how well educated many PB posters are with their abilities to dissect and discuss past studies and more. Now consider that Dr. Kendall, the former Chief Scientific Medical Officer for the ADA, has already done the same in much, much greater depth and concluded that the studies contain "veins of gold" and that Afrezza should be the standard of care. Mike too has said, "doctor's are shocked" when they hear the results. I'm hopeful the company's strategic plan is to bring clarity to these statements in a big way at the ADA and this will truly explode the scientific chatter that is the topic of this thread. If this chatter is paired with a new marketing push, it could be the game changer and paradigm shift we've waited over 10 years to see. IMO, I can't see how this is not going to happen. GL I don't think any amount of chattering here on proboards is going to impact scripts. Doctors are unlikely to see it, and they want cold hard trial results not poetic phrases. so dreamboat, mango put up the slide, advertisement to start ~ ADA. When these ratios, get put into %, I have seen this information included on the advertising of other Pharma. I will try it. The starting HbA1c is 7.98% for Afrezza and 7.88% for Novolog. Over the 24 weeks of the trial the Afrezza HbA1c dropped by 0.21% to 7.77% and the Novolog dropped by 0.40% to 7.48%. That make 0.21/7.98 = 0.0263 or 2.63% drop vs. 0.40/7.88 = 0.0508 or 5.08%. The confusion is because HbA1c is measured in percentage of Hb so everything is measured in percentages, both the HbA1c change, and the amount of change. Afrezza patients had fewer hypos than Aspart users (9.8 per subject-month vs 13.97 per subject-month) change in HbA1c over the treatment period (-0.21 % vs -0.4%). 14/100 x 10/x = 70. A 30 % decrease in hypoglycemia seen in studies. Afrezza users experienced 30% less hypoglycemia. Holdem told us two days ago. you know, How Jardiance / less heart attacks. (and more amputations) our problem is insurance coverage contracts Pharma has with the pharmacy business managers and their bonus package and incentive plans.
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Post by akemp3000 on Jun 6, 2018 16:57:50 GMT -5
Definitely meant scientific chatter in the industry...originating with Dr. Kendall & SAB then moving to ADA, endos and finally pcps and educators.
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Post by sayhey24 on Jun 6, 2018 19:46:35 GMT -5
Speaking scientific chatter there is lots of discussion of A1c versus TIR and is afrezza better or worse at reducing A1c. afrezza has one job and its not to reduce A1c. Its to get the PWD back to their fasting baseline asap (about 2 hours) while not causing hypoglycemia.
Prior to long-term basal and meal time insulin talking in terms of A1c made sense. In discussion of non-insulin non-mealtime anti-glycemics the discussion of A1c still makes sense since they neither reduce meatime glucose nor actively attempt to keep the PWD at baseline.
However, when talking a modern basal the goal is to keep the PWD steady at their baseline when fasting. A good example is Tresiba. When talking an RAA or afrezza the goal is to blunt the mealtime spike and get the PWD back to baseline asap. In both cases (basal and prandial) talking A1c to evaluate either is incorrect. If both where properly doing their jobs, to decrease A1c would amount to increasing the amount of the basal being taken to reduce the baseline which during fasting should remain flat.
Relying on the prandial to decrease A1c if the prandial was working properly is incorrect. In fact what it does point to is increased hypoglycemia. Yes, a prandial showing a greater reduction in A1c versus another prandial "working properly", is a BAD thing.
Two years ago on this board we were talking that use of CGMs would become standard practice. In two years the use of A1c when talking prandial medications won't be used anymore. We will be talking TIR. The problem we face here is we are about 2 years ahead of the community.
To demonstrate with a simple example of how little a prandail should effect A1c assume a non-diabetic with a fasting glucose baseline at 85 mg/dl assuming; they only eat 3 meals a day; their excursions peak at 125; they are back to baseline within 2 hours.
Fasting baseline A1c is 4.6 (assuming 18 hours) mealtime A1c is 5.3 (assuming 6 hours) Overall A1c is 4.7 (the mealtime excursion requiring a prandial should have little overall affect on A1c).
In theory, if the prandial is doing what it is suppose to do which is get the PWD back to baseline in about 2 hours whats affecting A1c is the baseline which should be adjusted with the basal. The problem however is Before Afrezza (BA) there was no prandial which worked the way it should. Additionally, prior to CGMs getting the AGP to know what was going on was near impossible.
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Post by agedhippie on Jun 6, 2018 20:28:38 GMT -5
Speaking scientific chatter there is lots of discussion of A1c versus TIR and is afrezza better or worse at reducing A1c. afrezza has one job and its not to reduce A1c. Its to get the PWD back to their fasting baseline asap (about 2 hours) while not causing hypoglycemia. Prior to long-term basal and meal time insulin talking in terms of A1c made sense. In discussion of non-insulin non-mealtime anti-glycemics the discussion of A1c still makes sense since they neither reduce meatime glucose nor actively attempt to keep the PWD at baseline. However, when talking a modern basal the goal is to keep the PWD steady at their baseline when fasting. A good example is Tresiba. When talking an RAA or afrezza the goal is to blunt the mealtime spike and get the PWD back to baseline asap. In both cases (basal and prandial) talking A1c to evaluate either is incorrect. If both where properly doing their jobs, to decrease A1c would amount to increasing the amount of the basal being taken to reduce the baseline which during fasting should remain flat. Relying on the prandial to decrease A1c if the prandial was working properly is incorrect. In fact what it does point to is increased hypoglycemia. Yes, a prandial showing a greater reduction in A1c versus another prandial "working properly", is a BAD thing. Two years ago on this board we were talking that use of CGMs would become standard practice. In two years the use of A1c when talking prandial medications won't be used anymore. We will be talking TIR. The problem we face here is we are about 2 years ahead of the community. To demonstrate with a simple example of how little a prandail should effect A1c assume a non-diabetic with a fasting glucose baseline at 85 mg/dl assuming; they only eat 3 meals a day; their excursions peak at 125; they are back to baseline within 2 hours. Fasting baseline A1c is 4.6 (assuming 18 hours) mealtime A1c is 5.3 (assuming 6 hours) Overall A1c is 4.7 (the mealtime excursion requiring a prandial should have little overall affect on A1c). In theory, if the prandial is doing what it is suppose to do which is get the PWD back to baseline in about 2 hours whats affecting A1c is the baseline which should be adjusted with the basal. The problem however is Before Afrezza (BA) there was no prandial which worked the way it should. Additionally, prior to CGMs getting the AGP to know what was going on was near impossible. There are a couple of things. The purpose of a basal is to keep your level flat, not to get you to a baseline. If you are doing that you are going to end up in trouble. The way a basal works if I am at 200 with no insulin onboard and I fast then I should remain at 200 until the basal wears of a day later. If I get back to my baseline, say 100, then I have got my basal badly wrong. Your HbA1c is a reflection of the area under the graph. If my level spikes to 250 every meal and stays there for two hours then my HbA1c is going to be much worse than if it spiked to 150 and stayed there for an hour. Prandial spikes have a big impact on HbA1c. Hypoglycemia does not have that much effect provided it is not happening repeatedly. Hypos tend to be brief downward spikes because they get corrected quickly (usually overcorrected which offsets the hypo) so area is not large. The HbA1c is basically the integral of that graph. This is why TIR has such an impact on HbA1c. If you can hold to a tight range then the integral is going to be smaller. If you keep having large extended peaks then the integral is going to be larger. I think somewhere Peppy posted something about how the percentage time in range mapped to reduction in HbA1c.
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Post by mnkdfann on Jun 6, 2018 21:09:53 GMT -5
The counter to that is going to be that it was achieved at the cost of a worse HbA1c outcome and that if the RAA arm had similarly underperformed their hypo rate would also be lower. That said I don't see a poster having a lot of impact, they need to get this published in a journal. In a good journal. If they publish in a Hindawi (or like) journal again, it will be pretty disappointing and of no significant value.
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Post by sayhey24 on Jun 7, 2018 5:26:50 GMT -5
Age - The purpose of a basal is to keep your level flat. If your baseline is 200 and you want to reduce it to 150 you need to increase the amount of basal being taking. The goal is to then stay flat out 150. This will reduce A1c. In theory if you never eat and you maitain that basal insulin level you will stay at 150.
The prandial's only job should be getting you back to baseline after meals. If your baseline is 200 then it should get you back to 200. If its 150 then it needs to get you back to 150. It's job is NOT to reduce A1c. Its job is to stop the spike and get you back to baseline asap.
As I demonstrated above the mealtime spike should have little impact on A1c. The problem to date is the RAAs don't do their jobs as they should. The good news is we now have a mealtime anti-glycemic in afrezza which actually can mimic first and second phase release.
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Post by peppy on Jun 7, 2018 5:50:46 GMT -5
Aged, I am glad you finally admitted— Aspart had a lower HbA1c because it caused more hypos.
Aged, I am a slow ship. You knew the better hbA1c the difference - .21 on a 7.98 scale, and .40 from a 7.88 scale, was the increased hypos. you were trying to tell me all along. Afrezza. 7.98% - 7.77% = .21 Hba1c which is measured in %. Novolog 7.88% - 7.48% = .40 hbA1c which is measured in %. Afrezza patients had fewer hypos than Aspart users (9.8 per subject-month vs 13.97 per subject-month) - change in HbA1c over the treatment period (-0.21 % vs -0.4%). Here is the latest greatest rub. The 2018 ADA guidelines, paraphrasing, "allow higher hbA1c targets to avoid hypos." additionally, a couple of paragraphs in 2018 standards of care , regarding the over time affect of hypos on cognitive function OVER TIME, years. If I look at it another way, the ada is changing their targets to work better with the hypo rate known with RAA's. Perhaps the use of CGM have pointed out the hypos at a continuous level. Sayhey did point out in a post, endocrinology moves at a snails pace. Hypoglycemia In type 2 diabetes, severe hypoglycemia is associated with reduced cognitive func- tion, and those with poor cognitive func- tion have more severe hypoglycemia. In a long-term study of older patients with type 2 diabetes, individuals with one or more recorded episode of severe hypo- glycemia had a stepwise increase in risk of dementia (37). Likewise, the ACCORD trial found that as cognitive function de- creased, the risk of severe hypoglycemia increased (38). Tailoring glycemic therapy may help to prevent hypoglycemia in in- dividuals with cognitive dysfunction. Hyperglycemia In those with type 2 diabetes, the degree and duration of hyperglycemia are re- lated to dementia. More rapid cognitive decline is associated with both increased A1C and longer duration of diabetes (34). The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study found that each 1% higher A1C level was associated with lower cognitive function in individu- als with type 2 diabetes (35). However, the ACCORD study found no difference in cognitive outcomes in participants ran- domly assigned to intensive and standard glycemic control, supporting the recom- mendation that intensive glucose control should not be advised for the improve- ment of cognitive function in individuals with type 2 diabetes (36). diabetesed.net/wp-content/uploads/2017/12/2018-ADA-Standards-of-Care.pdf In a recent report, mean glucose measured with CGM versus central labo- ratory–measured A1C in 387 participants in three randomized trials demonstrated that A1C may underestimate or overesti- mate mean glucose. Thus, as suggested, a patient’s CGM profile has considerable potential for optimizing his or her glyce- mic management (42). Recommendations - A reasonable A1C goal for many nonpregnant adults is ,7% (53 mmol/mol). A - Providers might reasonably suggest more stringent A1C goals (such as ,6.5% [48 mmol/mol]) for se- lected individual patients if this can be achieved without significant hypoglycemia or other adverse ef- fects of treatment (i.e., polyphar- macy). Appropriate patients might include those with short duration of diabetes, type 2 diabetes treated with lifestyle or metformin only, long life expectancy, or no signifi- cant cardiovascular disease. C - Less stringent A1C goals (such as ,8% [64 mmol/mol]) may be ap- propriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascu- lar or macrovascular complications, extensive comorbid conditions, or long-standing diabetes in whom the goal is difficult to achieve de- spite diabetes self-management education, appropriate glucose monitoring, and effective doses of multiple glucose-lowering agents including insulin. B - Hypoglycemia unawareness or one or more episodes of severe hypo- glycemia should trigger reevalua- tion of the treatment regimen. E - Insulin-treated patients with hy- poglycemia unawareness or an episode of clinically significant hy- poglycemia should be advised to raise their glycemic targets to strictly avoid hypoglycemia for at least several weeks in order to par- tially reverse hypoglycemia un- awareness and reduce risk of future episodes. A - Ongoing assessment of cognitive function is suggested with increased vigilance for hypoglycemia by the clinician, patient, and caregivers if low cognition or declining cognition is found. B Hypoglycemia is the major limiting factor in the glycemic management of type 1 and type 2 diabetes. Recommendations from the International Hypoglycemia Study Group regarding the classification of hypo- glycemia in clinical trials are outlined in Ta- ble 6.3 (75). Of note, this classification scheme considers a blood glucose ,54 mg/dL (3.0 mmol/L) detected by SMBG, CGM (for at least 20 min), or laboratory measurement of plasma glucose as suffi- ciently low to indicate clinically significant hypoglycemia Symptoms of hypoglycemia include, but are not limited to, shakiness, irritabil- ity, confusion, tachycardia, and hunger.
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Post by peppy on Jun 7, 2018 9:28:29 GMT -5
could it be said," afrezza (insulin human) met ADA HbA1c goal criteria with less hypoglycemia." "30% less hypoglycemia than Insulin aspart, (Novolog)". (?) www.rxlist.com/novolog-drug.htm
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Post by agedhippie on Jun 7, 2018 9:41:19 GMT -5
Age - The purpose of a basal is to keep your level flat. If your baseline is 200 and you want to reduce it to 150 you need to increase the amount of basal being taking. The goal is to then stay flat out 150. This will reduce A1c. In theory if you never eat and you maitain that basal insulin level you will stay at 150. The prandial's only job should be getting you back to baseline after meals. If your baseline is 200 then it should get you back to 200. If its 150 then it needs to get you back to 150. It's job is NOT to reduce A1c. Its job is to stop the spike and get you back to baseline asap. As I demonstrated above the mealtime spike should have little impact on A1c. The problem to date is the RAAs don't do their jobs as they should. The good news is we now have a mealtime anti-glycemic in afrezza which actually can mimic first and second phase release. That is not what your basal is for and you will end up in serious trouble if you use it like that. Basal should keep you flat regardless of baseline, you use the same amount of basal insulin if your baseline is 100 or 300. If you are flat at 200 on basal only and want to be flat at 150 then you correct with prandial insulin to get to 150, you do not increase your basal to do that. Basal insulin is there to cover basal glucose and basal glucose is constant day to day. I know this is how it works because it was what I was taught to do, and do every day You are correct about the role of prandial insulin, it is to return you to baseline, but wrong about the impact of meal time spikes on HbA1c. What matters in the area under the graph which is why Afrezza should outperform RAA since Afrezza gives a faster return to baseline reducing the area in the spike. HbA1c effectively performs an integration of your continuous glucose level. Your approach would only work if you knew the rate of glycation, and even then the curve would defeat a meaningful result.
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Post by agedhippie on Jun 7, 2018 9:54:28 GMT -5
could it be said," afrezza (insulin human) met ADA HbA1c goal criteria with less hypoglycemia." "30% less hypoglycemia than Insulin aspart, (Novolog)". (?) www.rxlist.com/novolog-drug.htmIt could, but the problem is the statistical significance. It is within the margin of error so the results could actually be reversed. Think of it like an opinion poll where the two candidates are withing the margin of error - one of them is going to win, but statistically it could have be either. If I was presenting the results I would give the chart with minimal commentary and let people draw their own (possibly incorrect) conclusion that Afrezza will reliably cause fewer hypos. While an endo will find the result interesting what they will want to see is the underlying data. Specifically were all those hypos from one person or were they spread through a group? The first case would make them discount the results, the second answer would give more credibility to the results. As an example Al said that most of the hypos in the Type 2 trial were due to one or two people which means the results were better than they looked.
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Post by peppy on Jun 7, 2018 12:36:48 GMT -5
could it be said," afrezza (insulin human) met ADA HbA1c goal criteria with less hypoglycemia." "30% less hypoglycemia than Insulin aspart, (Novolog)". (?) www.rxlist.com/novolog-drug.htm It could, but the problem is the statistical significance. It is within the margin of error so the results could actually be reversed. Think of it like an opinion poll where the two candidates are withing the margin of error - one of them is going to win, but statistically it could have be either. If I was presenting the results I would give the chart with minimal commentary and let people draw their own (possibly incorrect) conclusion that Afrezza will reliably cause fewer hypos. While an endo will find the result interesting what they will want to see is the underlying data. Specifically were all those hypos from one person or were they spread through a group? The first case would make them discount the results, the second answer would give more credibility to the results. As an example Al said that most of the hypos in the Type 2 trial were due to one or two people which means the results were better than they looked. JARDIANCE is the only type 2 diabetes pill proven to go beyond lowering A1C to reduce the risk of CV death for adults who have type 2 diabetes and heart disease.www.jardiance.com/?sc=JARACQWEBSEMGGL1408001&utm_source=google&utm_medium=cpc&utm_term=jardiance&utm_campaign=Branded_-_Jardiance_-_BMM&gclid=CjwKCAjwr-PYBRB8EiwALtjbz50IIQ-d2B4nfs8hy6427bUf34gIr9oOmPUMyRe1c1H2TRat6in-7xoCAF8QAvD_BwE&gclsrc=aw.dsThe Jardiance commercial saids proven to reduce CV death. The black box warning saids, amputation, bone fractures, infections. Help me out here. What is the statistical significance here? The commercial does not say amputation. it saids decreased blood volume.
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