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Post by zuegirdor on Aug 11, 2017 13:16:49 GMT -5
The future is nearly here. Its all about technology. Prior to CGMs PWDs had no idea what was going on, most doctors also had no idea and the ones which did hid behind the numbers. Once CGMs are widely used it will be difficult for doctors to hide behind the numbers and to keep prescribing something which does not work to address the main problem T2s have which is first phase insulin release and meal time spikes. Many of the T2 are spiking 180+, some 250+ at meal time and 90% are not meeting a 6.0 A1c. So no, metformin is not currently working. Heck, 70+% are not even meeting a target of 7.0 However, I misjudged the market a few years ago as I was focused on the T1/T2 market. When Tim Cook introduces the CGM IWatch it takes everything to a new level. "Non-diabetics" who are spiking over 130 at lunch are going to start looking to address their pre-diabetes. If VDex is correct on the hypo safety of afrezza, this market is way beyond anything I anticipated. The IWatch will not be about the PWD market, it will be about everyone else. The spiking guy at the lunch group is going to be saying "give me that little blue cartridge". Now, I have always thought keeping BG levels non-diabetic is directly tided to longevity. If they can show keeping a 70-130 range greatly improves heart health people will start taking afrezza just like the statins. Bottom line metformin is doomed along with the other T2 meds. As the good doctor who worked hard years ago to get metofrmin FDA approved Dr. Ralph DeFronzo from the University of Texas Health Science Center said at the BeyondA1c forum a few weeks ago “The most waste in type 2 diabetes is to continuously put people on metformin and sulfonylureas (glyburide, glimepiride, etc.). These drugs have no protective effect on the beta cell, and by the time you figure out what you’re doing, there are no beta cells left to save.” diatribe.org/the-diatribe-foundation-and-tcoyd-11th-annual-forumThe CGM iWatch that Tim Cook is wearing is the Dexcom app. To use it you need a Dexcom and if people don't like insulin needles they are going to love a CGM inserter. Contrary to what you think people are not going to want to obsess over their blood glucose levels, they are just not that engaged. You are trying to change lifestyles and that is extremely difficult to do. So no, I am with the good doctor, the future is not single drugs like metformin, as he says it's tailored drug cocktail with metformin as a constituent. Yes insulin will have a role but it's going to be as a last resort. Not that I like that approach, I would move to insulin after monotherapy failure, but it has the virtue of requiring minial change and in the end that approach wins. Perhaps this whole Afrezza thing is just a puff of smoke in a hurricane; and the amazing liberation from anxiety about blood sugar and carb counting and the average diabetic's loss of 13 years of lifespan that Afrezza users experience is just drug induced euphoria...?. But also consider: if your aunt had balls, she'd be your uncle!
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Post by dreamboatcruise on Aug 11, 2017 13:19:54 GMT -5
Great article! It needs to get exposure in current media. Published in November of 2009. Al addressed dosage quite clearly, "three times the amount" of injectable insulin. Interesting also to read the comments. While reading it, one can see why we longs invested in MNKD in the first place and are so very dedicated to AFREZZA'S success! Sad that Al is no longer here to see it through, but I think that we will! GLTA! I believe Al is talking about the actual amount of insulin in the cartridge rather than the supposedly RAA equivalent "units" that cartridges are designated. Surmising that because 3x is higher than I've seen anyone state for needing to increase RAA when using Afrezza and because of the cartridge sizes that Al states in the article.
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Post by sayhey24 on Aug 11, 2017 19:56:04 GMT -5
The future is nearly here. Its all about technology. Prior to CGMs PWDs had no idea what was going on, most doctors also had no idea and the ones which did hid behind the numbers. Once CGMs are widely used it will be difficult for doctors to hide behind the numbers and to keep prescribing something which does not work to address the main problem T2s have which is first phase insulin release and meal time spikes. Many of the T2 are spiking 180+, some 250+ at meal time and 90% are not meeting a 6.0 A1c. So no, metformin is not currently working. Heck, 70+% are not even meeting a target of 7.0 However, I misjudged the market a few years ago as I was focused on the T1/T2 market. When Tim Cook introduces the CGM IWatch it takes everything to a new level. "Non-diabetics" who are spiking over 130 at lunch are going to start looking to address their pre-diabetes. If VDex is correct on the hypo safety of afrezza, this market is way beyond anything I anticipated. The IWatch will not be about the PWD market, it will be about everyone else. The spiking guy at the lunch group is going to be saying "give me that little blue cartridge". Now, I have always thought keeping BG levels non-diabetic is directly tided to longevity. If they can show keeping a 70-130 range greatly improves heart health people will start taking afrezza just like the statins. Bottom line metformin is doomed along with the other T2 meds. As the good doctor who worked hard years ago to get metofrmin FDA approved Dr. Ralph DeFronzo from the University of Texas Health Science Center said at the BeyondA1c forum a few weeks ago “The most waste in type 2 diabetes is to continuously put people on metformin and sulfonylureas (glyburide, glimepiride, etc.). These drugs have no protective effect on the beta cell, and by the time you figure out what you’re doing, there are no beta cells left to save.” diatribe.org/the-diatribe-foundation-and-tcoyd-11th-annual-forumThe CGM iWatch that Tim Cook is wearing is the Dexcom app. To use it you need a Dexcom and if people don't like insulin needles they are going to love a CGM inserter. Contrary to what you think people are not going to want to obsess over their blood glucose levels, they are just not that engaged. You are trying to change lifestyles and that is extremely difficult to do. So no, I am with the good doctor, the future is not single drugs like metformin, as he says it's tailored drug cocktail with metformin as a constituent. Yes insulin will have a role but it's going to be as a last resort. Not that I like that approach, I would move to insulin after monotherapy failure, but it has the virtue of requiring minial change and in the end that approach wins. No, the IWatch Tim Cook has been wearing for about 6 months was made by Apple. The band is the CGM and I have been told about 200 people had been walking around the Bay Area with them. The rumor is Cook wants to launch it next year as a non-medical device. They say it works. Hopefully they are correct. I have never seen it, in person. What you are talking about with Dexcom is what was shown at Apple tech days last month. This is totally different than what Apple is doing. The good news is from a MNKD perspective the more CGMs the better. However Apple's is a device which opens up glucose monitoring to the world and makes it main stream. qz.com/958033/apple-appl-has-a-secret-glucose-monitoring-device-project-to-help-manage-diabetes-through-the-apple-watch/2If you actually listen to DeFronzo he is not talking about using metformin at all as part of his "new" cocktail. Now, 20+ years ago he was one of the biggest proponents of metformin but what he had realized is it does not work. In fact you could call him the "Father of Metformin in the U.S.". To put things in context his views of insulin are old school; its dangerous; its complicated; and between the finger sticks and injections its too much of a pain for his patients. In simple terms he was looking for a better way than old school insuliln. Six years ago he started a study in Qatar. I don't believe its published yet. The study used his "new cocktail" a combination of GKP-1 and TZD. What he learned was beta cells can actually be regenerated when you get the BG under control. If he had been reading this board he could have learned the same thing but at least he learned. So, his study is great news for afrezza because it further supports the direction to get the BG into range and beta cell regeneration can happen. And we all know nothing is better than afrezza to keep time in range. As far as afrezza and DeFronzo, afrezza was not an available "tool" for his study which started 6 years ago and it just does not fit his understanding of insulin. Its too far out of the box for him at this point since he is too invested and wed to his study and his cocktail of GLP-1 and TZD. Maybe in a few years when he starts seeing too many of his patients dropping dead from pancreatic cancer he will be ready to give afrezza a look. What he has said in addition to metformin and sulfonylureas should no longer be used, he also said the amputation rate for SLGT-2 users is a really big problem so he is staying away from them too. The one Big problem DeFronzo has with afrezza is its cost. He thinks its too damn expensive and his patients can not afford a $500 box of afrezza. I think we all agree with him on this.
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Post by agedhippie on Aug 11, 2017 21:02:37 GMT -5
If you actually listen to DeFronzo he is not talking about using metformin at all as part of his "new" cocktail. Now, 20+ years ago he was one of the biggest proponents of metformin but what he had realized is it does not work. In fact you could call him the "Father of Metformin in the U.S.". To put things in context his views of insulin are old school; its dangerous; its complicated; and between the finger sticks and injections its too much of a pain for his patients. In simple terms he was looking for a better way than old school insuliln. Six years ago he started a study in Qatar. I don't believe its published yet. The study used his "new cocktail" a combination of GKP-1 and TZD. What he learned was beta cells can actually be regenerated when you get the BG under control. Here you go: Abdul‐Ghani MA, Puckett C, Triplitt C, Maggs D, Adams J, Cersosimo E, DeFronzo RA. Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add‐on therapy in subjects with new‐onset diabetes. Results from the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT): a randomized trial. Diabetes, Obesity and Metabolism. 2015 Mar 1;17(3):268-75.This is the Qatar study (it references the above treatment of metformin, pioglitazone and exenatide as the preferred strategy). There is no claim in the paper that beta cells can be regenerated which is unsurprising as that has never been proven although a lot of research money is being spent on trying to do it.
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Post by sayhey24 on Aug 11, 2017 21:39:54 GMT -5
If you actually listen to DeFronzo he is not talking about using metformin at all as part of his "new" cocktail. Now, 20+ years ago he was one of the biggest proponents of metformin but what he had realized is it does not work. In fact you could call him the "Father of Metformin in the U.S.". To put things in context his views of insulin are old school; its dangerous; its complicated; and between the finger sticks and injections its too much of a pain for his patients. In simple terms he was looking for a better way than old school insuliln. Six years ago he started a study in Qatar. I don't believe its published yet. The study used his "new cocktail" a combination of GKP-1 and TZD. What he learned was beta cells can actually be regenerated when you get the BG under control. Here you go: Abdul‐Ghani MA, Puckett C, Triplitt C, Maggs D, Adams J, Cersosimo E, DeFronzo RA. Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add‐on therapy in subjects with new‐onset diabetes. Results from the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT): a randomized trial. Diabetes, Obesity and Metabolism. 2015 Mar 1;17(3):268-75.This is the Qatar study (it references the above treatment of metformin, pioglitazone and exenatide as the preferred strategy). There is no claim in the paper that beta cells can be regenerated which is unsurprising as that has never been proven although a lot of research money is being spent on trying to do it. The claim of beta cell regeneration was directly from DeFronzo. I am not sure this is the study he was referring to. He was talking about a revised study and he was really excited about the beta cell regeneration. Maybe they ran a modified version of this published study? I don't think the new study is published yet. That was the impression I was left with. It doesn't really matter. Clearly he was worked up at the BeyondA1c forum especially after hearing Edelman going on and on about afrezza. Something happened for him to have a change of heart and to say “The most waste in type 2 diabetes is to continuously put people on metformin and sulfonylureas (glyburide, glimepiride, etc.). These drugs have no protective effect on the beta cell, and by the time you figure out what you’re doing, there are no beta cells left to save.” diatribe.org/the-diatribe-foundation-and-tcoyd-11th-annual-forum Back in the 1920's they were using a Lilac extract to treat diabetes but then insulin was discovered and they stopped using it because it didn't really work. Whats old is new. Metformin still doesn't work. 90% of metformin users are not <6.1 and 70+% are not <7.1 Those are the numbers. We know you like metformin. We also know DeFronzo was the "Father of Metformin in the U.S.". We also know DeFronzo has learned the hard way. The great news is now T2s have afrezza. They don't need the metformins or GLP-1s or DDP-4 Is or SGLT-2s or any of the other poisons. What does VDex say "afrezza first, afrezza instead, afrezza always". I guess they also think metfromin is junk "its a gate way to more drugs, damn near irresponsible". Its hard to argue with that. www.seventhform.com/vdexvids/metforminproblem.mov
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Post by sayhey24 on Aug 11, 2017 22:09:33 GMT -5
OK - yes the revised study "Combination Therapy With Exenatide Plus Pioglitazone Versus Basal/Bolus Insulin in Patients With Poorly Controlled Type 2 Diabetes on Sulfonylurea Plus Metformin was published care.diabetesjournals.org/content/40/3/325 I am not seeing them using metformin in this study. It was GLP-1 and TZD. I am going to really need some time to review it. They are claiming better results with a GLP-1 and TZD than insulin??? What the heck kind of insulin were they using and how were they using it??? I would take tresiba and afrezza against their combo any day of the week and twice on Sundays.
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Post by mango on Aug 11, 2017 22:22:36 GMT -5
If you actually listen to DeFronzo he is not talking about using metformin at all as part of his "new" cocktail. Now, 20+ years ago he was one of the biggest proponents of metformin but what he had realized is it does not work. In fact you could call him the "Father of Metformin in the U.S.". To put things in context his views of insulin are old school; its dangerous; its complicated; and between the finger sticks and injections its too much of a pain for his patients. In simple terms he was looking for a better way than old school insuliln. Six years ago he started a study in Qatar. I don't believe its published yet. The study used his "new cocktail" a combination of GKP-1 and TZD. What he learned was beta cells can actually be regenerated when you get the BG under control. Here you go: Abdul‐Ghani MA, Puckett C, Triplitt C, Maggs D, Adams J, Cersosimo E, DeFronzo RA. Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add‐on therapy in subjects with new‐onset diabetes. Results from the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT): a randomized trial. Diabetes, Obesity and Metabolism. 2015 Mar 1;17(3):268-75.This is the Qatar study (it references the above treatment of metformin, pioglitazone and exenatide as the preferred strategy). There is no claim in the paper that beta cells can be regenerated which is unsurprising as that has never been proven although a lot of research money is being spent on trying to do it. Beta cells express all the components of the endocannabinoid system. It is the endogenous cannabinoids and CB receptors that modulate beta cell function, survival, and proliferation. The ECS in beta cells regulate basal and glucose-induced insulin secretion. In an dysfunctional ECS, like in diabetes, but let's just take T2D as an example here. By administering exogenous cannabinoids, CBD and THCV, both of which are CB1 receptor antagonists, will induce beta cell protection and survival and proliferation while reducing apoptosis. The CB2 receptor also plays a role in this this inducing protective mechanisms and turning on fat burning. The only thing that is going to save beta cells is cannabinoids. Your beta cells are regulated by the endocannabinoid system. It's not that hard to see what needs to be done here. The endocannabinoid system is also responsible for the regulation of the microstructure of the pancreatic islets while a fetus is developing inside the mother's womb. Common ya'll quit talking about all this pharmaceutical crap and WAKE UP.
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Post by sayhey24 on Aug 12, 2017 7:26:09 GMT -5
Here you go: Abdul‐Ghani MA, Puckett C, Triplitt C, Maggs D, Adams J, Cersosimo E, DeFronzo RA. Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add‐on therapy in subjects with new‐onset diabetes. Results from the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT): a randomized trial. Diabetes, Obesity and Metabolism. 2015 Mar 1;17(3):268-75.This is the Qatar study (it references the above treatment of metformin, pioglitazone and exenatide as the preferred strategy). There is no claim in the paper that beta cells can be regenerated which is unsurprising as that has never been proven although a lot of research money is being spent on trying to do it. Beta cells express all the components of the endocannabinoid system. It is the endogenous cannabinoids and CB receptors that modulate beta cell function, survival, and proliferation. The ECS in beta cells regulate basal and glucose-induced insulin secretion. In an dysfunctional ECS, like in diabetes, but let's just take T2D as an example here. By administering exogenous cannabinoids, CBD and THCV, both of which are CB1 receptor antagonists, will induce beta cell protection and survival and proliferation while reducing apoptosis. The CB2 receptor also plays a role in this this inducing protective mechanisms and turning on fat burning. The only thing that is going to save beta cells is cannabinoids. Your beta cells are regulated by the endocannabinoid system. It's not that hard to see what needs to be done here. The endocannabinoid system is also responsible for the regulation of the microstructure of the pancreatic islets while a fetus is developing inside the mother's womb. Common ya'll quit talking about all this pharmaceutical crap and WAKE UP. Mango - should we be smoking the dope or are we all just dopes? What the heck is RLS doing?
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Post by agedhippie on Aug 12, 2017 7:58:33 GMT -5
OK - yes the revised study "Combination Therapy With Exenatide Plus Pioglitazone Versus Basal/Bolus Insulin in Patients With Poorly Controlled Type 2 Diabetes on Sulfonylurea Plus Metformin was published care.diabetesjournals.org/content/40/3/325 I am not seeing them using metformin in this study. It was GLP-1 and TZD. I am going to really need some time to review it. They are claiming better results with a GLP-1 and TZD than insulin??? What the heck kind of insulin were they using and how were they using it??? I would take tresiba and afrezza against their combo any day of the week and twice on Sundays. I also noticed a line in there that says the study is on-going so I think you are right and this is not the end result. I think for the insulin they either have not titrated it correctly, or people are skipping doses when they eat. That can be a problem in Type 2 since the immediate impact is more muted (a Type 2 will go high, but a Type 1 will both go high and go into ketosis risking DKA).
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Post by Deleted on Aug 14, 2017 14:10:26 GMT -5
A coworker that inquired about the trial by email received a reply with for inclusion and exclusion. Unfortunately, he doesn't qualify.
If he did, a dialog would start in September.
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Post by itellthefuture777 on Aug 15, 2017 12:22:16 GMT -5
One Drop device an indirect competitor device to Dexcom?...if so...and if sucessful trial...could be a good candidate for Google's..Alphabet's..Verily Life Science as Diabetes tech is Google primary focus...hmmmm
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Post by mnholdem on Aug 15, 2017 12:53:04 GMT -5
That's a nice thought, but their goal is a wireless continuous glucose measuring device that is non-invasive. Even though it's impressive, OneDrop is still a device that requires taking blood samples. Both will have Bluetooth capabilities, but OneDrop is not a CGM.
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Post by itellthefuture777 on Aug 16, 2017 18:15:24 GMT -5
Aren't most Type 2s currently treated with a basal insulin only, instead of mealtime dosing?
Yes, but that's the wrong way around. The correct therapy should be a good prandial insulin and not long-term insulin — Afrezza in particular because it turns off glucose production and delivery from the liver. Our latest trials of 600 patients are showing even more significant benefits from the product than our original trials; the most recent trial appears to show that this should replace frontline treatment for all Type 2 patients.
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Post by itellthefuture777 on Aug 16, 2017 18:23:29 GMT -5
I can see Dexcom..and Verily Life Sciences adding One Drop...Also..I can see ALL hexomeric insulins are in a state of flat-line...saturated market...they are over...The worlds only inhaled monomeric prandial insulin is also the only FDA approved insulin set for growth...Large pharma Novo Nordisk has some decisions to make...growth is over for them...if they don't act...and they know it...
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Post by sayhey24 on Aug 16, 2017 19:25:01 GMT -5
I can see Dexcom..and Verily Life Sciences adding One Drop...Also..I can see ALL hexomeric insulins are in a state of flat-line...saturated market...they are over...The worlds only inhaled monomeric prandial insulin is also the only FDA approved insulin set for growth...Large pharma Novo Nordisk has some decisions to make...growth is over for them...if they don't and they know it... Itell - Dexcom to One Drop - done www.seapeptide.com/single-post/2016/11/10/Analyzing-Data-With-One-DropHere is the issue with Verily. They will be competing with One Drop. They own 50% of Onduo which is building their own monitoring/dosing/performance based insurance business. They started thinking dosing was going to be a very hard problem. Then they realized between Tresiba and afrezza most of the variables have been eliminated and its a simple flow control problem. They are suppose to launch in 2018 so they should be announcing their product offering soon. Dr. Steve Edelman, afrezza user and advocate is the architect of the Ondou protocol. While we don't know what the protocol will be yet a pretty good assumption is the good doctor will be incorporating at least part of what he is personally using, afrezza. Incorporating Tresiba is probably not going to happen since Sanofi owns the other 50% and they are probably going to want Toujeo as the main basal. In the case of T2s if they follow the VDex protocol with afrezza first, the PWDs will never progress to a basal so the Toujeo sales will not be that much anyway.
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