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Post by agedhippie on Feb 8, 2017 19:56:56 GMT -5
agedhippie "For Type 2 I would expect an endo to leave the patient on metformin even if they prescribed Afrezza. Metformin reduces the amount of insulin required by reducing insulin resistance." Are there studies that back your claim? Probably but it doesn't really matter, it's what they will do. The ADA guidelines have the addition of basal and then the addition of bolus insulin to make a triple drug combination. These are additive, they don't halt one to start the next.
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Post by Deleted on Feb 8, 2017 20:24:40 GMT -5
I emailed Castagna asking how does MannKind recommend prescribing Afrezza for T2s on metformin. If/when I receive a reply I will post.
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Post by dreamboatcruise on Feb 8, 2017 20:38:33 GMT -5
Afrezza takes away dose size as an issue (or rather it dramatically reduces it) however it requires multiple doses during the day with follow-up testing and potentially a correction dose for each meal. Metformin is one pill a day. That's going to be the compliance issue. I say this as an insulin user because that is also how you are meant to use RAA, but I don't know anyone who does the follow-up test and dose! For Type 2 I would expect an endo to leave the patient on metformin even if they prescribed Afrezza. Metformin reduces the amount of insulin required by reducing insulin resistance. That is a huge issue with Type 2 where you can be taking a lot of insulin - 1u per 1g of carbs is not unusual so you can easily be looking at 50u per meal. Though one wonders whether if started earlier enough, Afrezza might be able to greatly slow or halt progression with some simple protocol such as if meal has over Xg carbs inhale a 4u 10 min after starting meal. Maybe that relieves enough stress on beta cells if done very early in progression. No need to for meter or testing. Perhaps. Too bad MNKD doesn't have the resources to pursue clinical trials along this line.
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Post by sayhey24 on Feb 9, 2017 7:56:22 GMT -5
"Thinking would need to change" - there is the big nut for MNKD. If the goal was to stop the progression, the beta cells need a rest instead of being asked to work harder and produce more insulin by metformin. You are confusing sulfonylureas, like glipizide, with metformin. Metformin does not have that action. Metformin is a little tricky. It does three basic things. It limits the liver from dumping sugar in the blood. It also activates AMP Kinase to help uptake and it boosts GLP1 levels after eating. Its the later which is asking the pancreas to work harder when it needs to rest. Worse is if the PWD is using afrezza they don't want to have the liver effected by metofrmin as the afrezza insulin release will mimic phase 1 and get the liver back in sync. Using metformin just adds a second variable which is not only not needed but can give unpredictable results when trying to titrate. It better to just stop using it, IMO. But then again I am one of the first saying this.
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Post by sayhey24 on Feb 9, 2017 8:05:30 GMT -5
I emailed Castagna asking how does MannKind recommend prescribing Afrezza for T2s on metformin. If/when I receive a reply I will post. Kastanes - I am interested in hearing his reply and seeing the study results this is based on. If afrezza is mimicing the pancreatic release for phase 1 and working properly with the liver to shut down sugar secretion, taking metformin not only has no benefit but adds a second variable making the dosing of afrezza a little harder. I would really be interested is understanding the rational. Once they start proper second dosing for phase 2 release which is not discussed in the starter kit its better to just be dealing with one variable in the dosing equation.
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Post by mango on Feb 16, 2017 22:52:30 GMT -5
As the Diabetes and AD rates increase, so does the naive widespread use to certain medications, including: • Metformin —Metformin is a fluorescent molecule able to reach the brain —Chronic metformin treatment stimulates APP processing mainly in brain cortex region —Metformin induces accumulation of Aβ aggregates mainly in brain cortex region —Metformin induces mitochondrial dysfunction by impairing MPT pores and membrane channels —Metformin induces neuronal apoptosis —Metformin directly interacts with Aβ peptide influencing its aggregation kinetics in vitro —Metformin treatment changes the levels of expression of TOM40, VDAC1 and HKI, proteins involved in mitochondrial import and export of molecules and metabolites, in cortex region where Aβ aggregates are mainly present. Studies on human brain biopsies have demonstrated that TOM40 pore mediates the internalization of Aβ and APP —Metformin Increases Aβ Generation —Metformin Up-Regulates BACE1 Promoter Activity —Metformin's Effect Is Independent of Glucose Metabolism and Insulin Signaling —Metformin's Effect Is Mediated by Activation of the AMP Kinase (AMPK) in Vitro and in Vivo. —Antagonizing Effect on Intracellular Aβ Generation —Metformin induces APP expression and processing via oxidative stress — Insulin plays a protective role against metformin by oxidative stress inhibition—Metformin triggers APP and presenilin via NFκB activation —Metformin Facilitates Amyloid-β Generation by β- and γ-Secretases via Autophagy Activation www.ncbi.nlm.nih.gov/pmc/articles/PMC5032692/m.pnas.org/content/106/10/3907.long?view=long&pmid=19237574ac.els-cdn.com/S0167488915000324/1-s2.0-S0167488915000324-main.pdf?_tid=5796efb8-f4c3-11e6-9ea2-00000aab0f01&acdnat=1487303230_c084c701970fe76391f9a5ac2de3d152content.iospress.com/articles/journal-of-alzheimers-disease/jad151200
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