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Post by LosingMyBullishness on Sept 20, 2016 17:49:17 GMT -5
Appreciate the guidance...one last question...is Metformin, in and of itself, a dangerous drug or is it simply a drug with bad side effects which eventually leads to other diabetic drugs that are even worse? If your kidneys are not damaged (eGFR of under 45) then Metformin is fine. The FDA Drug Safety Communication covers Metformin specifically for it's use in people with reduced kidney function but also includes the general review of Metformin. Make sure that you get the extended release version of Metformin, and start at 1000mg or less to avoid a lot of problems. It takes about a month to become effective (slow accumulation). Maximum dosage is 2250mg per day but you shouldn't be at that level. The side effects largely go away after the first month. Be aware that Metformin does not always work. Some people have genetics that prevents them from metabolizing it although that is fairly rare. Metformin is the most effective of the oral meds and has the least side effects. Type 2 is progressive, live long enough and everyone ends up on insulin.  How does that all make sense. It is fine if your kidney are okay..take at least 1000mg to avoid a lot of problems...most side effects go away after 1 months..it is the oraled with the least side effects.. So there are side effects even with healthy kidneys and that is just fine? So why not take Afrezza to deal with the meantime peaks andafter dome time add a basal insulin? Why are you and this class of India so keen on metformin ? And why are metformin's side effects fine? |
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Post by agedhippie on Sept 20, 2016 18:28:15 GMT -5
If your kidneys are not damaged (eGFR of under 45) then Metformin is fine. The FDA Drug Safety Communication covers Metformin specifically for it's use in people with reduced kidney function but also includes the general review of Metformin. Make sure that you get the extended release version of Metformin, and start at 1000mg or less to avoid a lot of problems. It takes about a month to become effective (slow accumulation). Maximum dosage is 2250mg per day but you shouldn't be at that level. The side effects largely go away after the first month. Be aware that Metformin does not always work. Some people have genetics that prevents them from metabolizing it although that is fairly rare. Metformin is the most effective of the oral meds and has the least side effects. Type 2 is progressive, live long enough and everyone ends up on insulin. How does that all make sense. It is fine if your kidney are okay..take at least 1000mg to avoid a lot of problems...most side effects go away after 1 months..it is the oraled with the least side effects.. So there are side effects even with healthy kidneys and that is just fine? So why not take Afrezza to deal with the meantime peaks andafter dome time add a basal insulin? Why are you and this class of India so keen on metformin ? And why are metformin's side effects fine? They wanted advice on metformin. That was my answer. Let me help you with your questions now. So there are side effects even with healthy kidneys and that is just fine? - Yes. All drugs have side effects, even insulin. So why not take Afrezza to deal with the meantime peaks andafter dome time add a basal insulin? - Because he did not have that option. Why are you and this class of India so keen on metformin ? - I have absolutely no idea what this means. And why are metformin's side effects fine? - You are repeating yourself, that was your first question and the answer is still the same. |
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Post by peppy on Sept 20, 2016 19:28:55 GMT -5
Diagnosed with T2 a year ago - for 3 years prior to that doctors tried to put me on Metformin, which I resisted. After diagnosis my A1c has ranged from 6.6 to 7.2. Endo prescribed Metformin despite my request to be put on Afrezza. Endo has prescribed Afrezza for T1 previously, so is not averse to Afrezza. Would appreciate suggestions on how to convince him to allow me to take Afrezza. Also welcome suggestions for medical literature citing the drawbacks of Metformin. The question, why metformin and not afrezza? www.goodrx.com/metformin
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Post by LosingMyBullishness on Sept 21, 2016 0:19:01 GMT -5
How does that all make sense. It is fine if your kidney are okay..take at least 1000mg to avoid a lot of problems...most side effects go away after 1 months..it is the oraled with the least side effects.. So there are side effects even with healthy kidneys and that is just fine? So why not take Afrezza to deal with the meantime peaks andafter dome time add a basal insulin? Why are you and this class of India so keen on metformin ? And why are metformin's side effects fine? They wanted advice on metformin. That was my answer. Let me help you with your questions now. So there are side effects even with healthy kidneys and that is just fine? - Yes. All drugs have side effects, even insulin. So why not take Afrezza to deal with the meantime peaks andafter dome time add a basal insulin? - Because he did not have that option. Why are you and this class of India so keen on metformin ? - I have absolutely no idea what this means. And why are metformin's side effects fine? - You are repeating yourself, that was your first question and the answer is still the same. Sorry aged, Was late and the spell checker already asleep. I will have a look at the link and see what the argumentation is.all have side effects are a rather vague answer. |
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Post by radgray68 on Sept 21, 2016 20:14:47 GMT -5
This is a serious question to my mind. If a body is lacking the proper amounts of insulin, why would you give it anything else? If a patient lacks oxygen, we give them oxygen. If they're deficient for vitamin D, we give them vitamin D. And so on, and so on. I have written to Mannkind about this, to no avail, inquiring about the possibility of a clinical trial for new T2's who have not yet started and meds. Post prandial spikes are the first thing to get ahold of are they not? My responses from the company have been that my inquiry has been forwarded to Ray Urbanski for follow-up. I know he's probably more than a little busy right now, and it's a loaded question with lots of facets, so I do understand the delay. I thought perhaps this board and the many diabetics reading it might have insights I haven't considered.
Many may know me from other sites, I have been around for about 5 years now and have read just about everything ever published about Mannkind. Still, I have yet to get an acceptable answer to my question. Why not Afrezza as a monotherapy for early T2's? A small clinical trial that leaves out all the other orals and includes CGM's is all we would need right? T2's are started on basal doses instead of prandial insulin when the numerous orals ultimately fail. Trials 171 and 175 had all kinds of other meds being taken by the participants and I think that hindered/hid Afrezza's true benefit.
Any insights are appreciated. Thanks. |
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Post by centralcoastinvestor on Sept 21, 2016 20:25:46 GMT -5
This is a serious question to my mind. If a body is lacking the proper amounts of insulin, why would you give it anything else? If a patient lacks oxygen, we give them oxygen. If they're deficient for vitamin D, we give them vitamin D. And so on, and so on. I have written to Mannkind about this, to no avail, inquiring about the possibility of a clinical trial for new T2's who have not yet started and meds. Post prandial spikes are the first thing to get ahold of are they not? My responses from the company have been that my inquiry has been forwarded to Ray Urbanski for follow-up. I know he's probably more than a little busy right now, and it's a loaded question with lots of facets, so I do understand the delay. I thought perhaps this board and the many diabetics reading it might have insights I haven't considered.
Many may know me from other sites, I have been around for about 5 years now and have read just about everything ever published about Mannkind. Still, I have yet to get an acceptable answer to my question. Why not Afrezza as a monotherapy for early T2's? A small clinical trial that leaves out all the other orals and includes CGM's is all we would need right? T2's are started on basal doses instead of prandial insulin when the numerous orals ultimately fail. Trials 171 and 175 had all kinds of other meds being taken by the participants and I think that hindered/hid Afrezza's true benefit.
Any insights are appreciated. Thanks. Welcome aboard radgray68! I really enjoyed your posts on the YMB over the years. I counted you as one of the must reads whenever you posted. In referring to your post, I believe Al Mann stated exactly what you mentioned above. That Afrezza would eventually be used as a monotherapy for early T2's. Al believed that it was entirely plausible that if treated soon enough with insulin, T2s could experience diabetic remission because the pancreas would get to "rest" during Afrezza therapy and get healthy again. |
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Post by mnkdkarma on Sept 21, 2016 22:32:45 GMT -5
Thanks for the insights = hope to see Urbanski's response posted once it's available. I am working to lower my A1c thru diet and exercise and holding off on taking Metformin as long as I possibly can. Would love to get in on any possible Afrezza and CGM trial for early T2s.
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Post by agedhippie on Sept 22, 2016 7:42:48 GMT -5
This is a serious question to my mind. If a body is lacking the proper amounts of insulin, why would you give it anything else? If a patient lacks oxygen, we give them oxygen. If they're deficient for vitamin D, we give them vitamin D. And so on, and so on. I have written to Mannkind about this, to no avail, inquiring about the possibility of a clinical trial for new T2's who have not yet started and meds. Post prandial spikes are the first thing to get ahold of are they not? My responses from the company have been that my inquiry has been forwarded to Ray Urbanski for follow-up. I know he's probably more than a little busy right now, and it's a loaded question with lots of facets, so I do understand the delay. I thought perhaps this board and the many diabetics reading it might have insights I haven't considered.
Many may know me from other sites, I have been around for about 5 years now and have read just about everything ever published about Mannkind. Still, I have yet to get an acceptable answer to my question. Why not Afrezza as a monotherapy for early T2's? A small clinical trial that leaves out all the other orals and includes CGM's is all we would need right? T2's are started on basal doses instead of prandial insulin when the numerous orals ultimately fail. Trials 171 and 175 had all kinds of other meds being taken by the participants and I think that hindered/hid Afrezza's true benefit.
Any insights are appreciated. Thanks. Here goes  Type 2 in it's early stages which is what we are talking about here is not due to an absolute insulin deficiency as with Type 1, but rather a relative insulin deficiency caused by insulin resistance. Your body is still making insulin, actually it is making far more than it would if you were not diabetic, but the insulin resistance is making it progressively less effective. This is a bit of a simplification because there are cases of Type 2 (lean Type 2) where it appears that there is an absolute deficiency although no antibody activity, and others like the Flatbush variant where the beta cells shut down but don't die. The classic Type 2 however has insulin resistance as the chief cause of their diabetes initially. The reason for that 'initially' is complicated and I can go into it later if people are really having trouble sleeping - meanwhile it's not relevant to the initial drug discussion because it's down the trail. So why metformin and not insulin? It comes back to the insulin resistance, compliance, safety, and of course cost. Metformin decreases the liver glucose production and improves peripheral insulin sensitivity. The reduced liver glucose output in turn reduces the insulin you need to absorb that glucose (incidentally this is why Type 1 diabetics are sometimes put on metformin), and the reduced insulin resistance makes what there is work better. This extends the runway before you need other drugs because you are back to living within the insulin your body naturally produces. Note that unlike sulphas metformin does this by reducing the need for insulin and not by wringing more out of your beta cells which is not good. The other points are self-evident. It is a lot easier to get people to take one pill a day than to take insulin at every meal and inbetween as well. Lifestyle changes are very difficult to maintain so the minimum change has the best chance of taking (this is also why low carb diet doesn't get seriously pushed these days). Cost? Metformin is generic, easy to manufacture (it's basic ingredient has been used for hundreds of years), costs cents vs. $10+ per day. Once you look at the number of diabetics it's hard to see how you can fund insulin broadly. And safety, metformin is, insulin isn't - it will cause hypos. In short; it's very well understood, it works, and it's dirt cheap. What it is not is a cure, and depending on the variant of the Type 2 (there are over 100 genes so thousands of variants) it odds are that it is going to fail in the end although in a lot of cases it will be sufficient alone according to the UKDPS (UKDPS was the only large scale Type 2 specific longitudinal study). |
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Post by sophie on Sept 22, 2016 12:03:20 GMT -5
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Post by babaoriley on Sept 22, 2016 13:33:03 GMT -5
This is a serious question to my mind. If a body is lacking the proper amounts of insulin, why would you give it anything else? If a patient lacks oxygen, we give them oxygen. If they're deficient for vitamin D, we give them vitamin D. And so on, and so on. I have written to Mannkind about this, to no avail, inquiring about the possibility of a clinical trial for new T2's who have not yet started and meds. Post prandial spikes are the first thing to get ahold of are they not? My responses from the company have been that my inquiry has been forwarded to Ray Urbanski for follow-up. I know he's probably more than a little busy right now, and it's a loaded question with lots of facets, so I do understand the delay. I thought perhaps this board and the many diabetics reading it might have insights I haven't considered.
Many may know me from other sites, I have been around for about 5 years now and have read just about everything ever published about Mannkind. Still, I have yet to get an acceptable answer to my question. Why not Afrezza as a monotherapy for early T2's? A small clinical trial that leaves out all the other orals and includes CGM's is all we would need right? T2's are started on basal doses instead of prandial insulin when the numerous orals ultimately fail. Trials 171 and 175 had all kinds of other meds being taken by the participants and I think that hindered/hid Afrezza's true benefit.
Any insights are appreciated. Thanks. Here goes Type 2 in it's early stages which is what we are talking about here is not due to an absolute insulin deficiency as with Type 1, but rather a relative insulin deficiency caused by insulin resistance. Your body is still making insulin, actually it is making far more than it would if you were not diabetic, but the insulin resistance is making it progressively less effective. This is a bit of a simplification because there are cases of Type 2 (lean Type 2) where it appears that there is an absolute deficiency although no antibody activity, and others like the Flatbush variant where the beta cells shut down but don't die. The classic Type 2 however has insulin resistance as the chief cause of their diabetes initially. The reason for that 'initially' is complicated and I can go into it later if people are really having trouble sleeping - meanwhile it's not relevant to the initial drug discussion because it's down the trail. So why metformin and not insulin? It comes back to the insulin resistance, compliance, safety, and of course cost. Metformin decreases the liver glucose production and improves peripheral insulin sensitivity. The reduced liver glucose output in turn reduces the insulin you need to absorb that glucose (incidentally this is why Type 1 diabetics are sometimes put on metformin), and the reduced insulin resistance makes what there is work better. This extends the runway before you need other drugs because you are back to living within the insulin your body naturally produces. Note that unlike sulphas metformin does this by reducing the need for insulin and not by wringing more out of your beta cells which is not good. The other points are self-evident. It is a lot easier to get people to take one pill a day than to take insulin at every meal and inbetween as well. Lifestyle changes are very difficult to maintain so the minimum change has the best chance of taking (this is also why low carb diet doesn't get seriously pushed these days). Cost? Metformin is generic, easy to manufacture (it's basic ingredient has been used for hundreds of years), costs cents vs. $10+ per day. Once you look at the number of diabetics it's hard to see how you can fund insulin broadly. And safety, metformin is, insulin isn't - it will cause hypos. In short; it's very well understood, it works, and it's dirt cheap. What it is not is a cure, and depending on the variant of the Type 2 (there are over 100 genes so thousands of variants) it odds are that it is going to fail in the end although in a lot of cases it will be sufficient alone according to the UKDPS (UKDPS was the only large scale Type 2 specific longitudinal study). Agedhippie, that's a really good explanation, and illustrates some of our headwinds. I can't speak to how accurate your statements are, but you have shown yourself over much time to be a pretty sharp guy, especially for one with your handle and all it implies!  |
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Post by scottiemac on Sept 22, 2016 13:34:46 GMT -5
Odd this should appear just now. I have an appointment with my doctor tomorrow to address what might be an uncommon side effect of Metformin. Started at 500mg twice a day in June 2015, doubled to 1000mg twice a day last November (glucose has dropped from 187.4 to 122.7 , A1c from 8.8 to 6.6% in July, next regular visit is November.) No insulin or related meds except Metformin, also take vitamins B6, B12, D3, and Losartan for hypertension. Torsemide for fluid retention (10 mg) was added a few months ago.
Not long after starting Metformin, I developed bruising on my right shin, and to a lesser effect, just below my calf with redness, tender like sunburn. Both my doctor and I noted it but at first it seemed to be easy bruising due to thin skin and age. Over time, after the dosage was bumped, the same developed to a lesser degree on my left shin and lower leg. As of about 10 days ago it had become plug ugly, gotten redder and purplier and spread. Bits of skin have peeled off leaving shine and not much else. My mother had a history of varicose veins but I do not. It could well be something vascular but, having stopped Metformin 10 days ago the area is now mildly improved, less redness and tenderness to touch. There is no deep pain or shortness of breath (DVT hallmarks) and the fact that there is improvement while off Metformin leads me to believe I may be having a reaction to it, and not in a good way. When I see my doctor tomorrow I am going to propose staying off Metformin until my regularly scheduled visit in 8 weeks. Clearly, if whatever this is comes roaring back or otherwise deteriorates she will be getting another call. If it clears, I'm done with it. I have lost 30 pounds in 15 months (another 75-90 to go, for my own personal goal) and track my foods and exercise daily. Fortunately the heat is finally over for the year and I can go back to walking a lot more and burn off more weight.
Anybody else have a similar derm reaction?
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Post by peppy on Sept 22, 2016 13:53:50 GMT -5
Odd this should appear just now. I have an appointment with my doctor tomorrow to address what might be an uncommon side effect of Metformin. Started at 500mg twice a day in June 2015, doubled to 1000mg twice a day last November (glucose has dropped from 187.4 to 122.7 , A1c from 8.8 to 6.6% in July, next regular visit is November.) No insulin or related meds except Metformin, also take vitamins B6, B12, D3, and Losartan for hypertension. Torsemide for fluid retention (10 mg) was added a few months ago.
Not long after starting Metformin, I developed bruising on my right shin, and to a lesser effect, just below my calf with redness, tender like sunburn. Both my doctor and I noted it but at first it seemed to be easy bruising due to thin skin and age. Over time, after the dosage was bumped, the same developed to a lesser degree on my left shin and lower leg. As of about 10 days ago it had become plug ugly, gotten redder and purplier and spread. Bits of skin have peeled off leaving shine and not much else. My mother had a history of varicose veins but I do not. It could well be something vascular but, having stopped Metformin 10 days ago the area is now mildly improved, less redness and tenderness to touch. There is no deep pain or shortness of breath (DVT hallmarks) and the fact that there is improvement while off Metformin leads me to believe I may be having a reaction to it, and not in a good way. When I see my doctor tomorrow I am going to propose staying off Metformin until my regularly scheduled visit in 8 weeks. Clearly, if whatever this is comes roaring back or otherwise deteriorates she will be getting another call. If it clears, I'm done with it. I have lost 30 pounds in 15 months (another 75-90 to go, for my own personal goal) and track my foods and exercise daily. Fortunately the heat is finally over for the year and I can go back to walking a lot more and burn off more weight.
Anybody else have a similar derm reaction? scottie, ask your physician and the physicians. The bruising sounds like your liver and clotting factors to me. (I can be wrong)
The liver plays a role in the production of clotting factors as well as red blood cell production. Some of the proteins synthesized by the liver include coagulation factors I (fibrinogen), II (prothrombin), V, VII, VIII, IX, X, XI, XIII, as well as protein C, protein S and antithrombin. en.wikipedia.org/wiki/Liver
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Post by radgray68 on Sept 22, 2016 14:02:48 GMT -5
Thanks for the reply Aged. And Sophie, I saw that article when it came out. We are going up against cost, storage requirements and ease of use when trying to bump Metformin. I just can't shake the comments Al made about the product way back when. Monomers seem to signal the liver, but it has never been thoroughly evaluated specifically for that effect, as far as I know. The "Paradigm Shift" is a lot harder to make in the face of these cost and ease of use issues. I know bloodletting was very popular for centuries.
I'm always going to be in Mannkind's corner. I know just enough science to make Afrezza seem like it should be a no-brainer to BP and insurance companies. Almost every week, I take x-rays on infected diabetic foot ulcers to check for boney involvement. Current treatments are failing.
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Post by scottiemac on Sept 22, 2016 16:42:24 GMT -5
Odd this should appear just now. I have an appointment with my doctor tomorrow to address what might be an uncommon side effect of Metformin. Started at 500mg twice a day in June 2015, doubled to 1000mg twice a day last November (glucose has dropped from 187.4 to 122.7 , A1c from 8.8 to 6.6% in July, next regular visit is November.) No insulin or related meds except Metformin, also take vitamins B6, B12, D3, and Losartan for hypertension. Torsemide for fluid retention (10 mg) was added a few months ago.
Not long after starting Metformin, I developed bruising on my right shin, and to a lesser effect, just below my calf with redness, tender like sunburn. Both my doctor and I noted it but at first it seemed to be easy bruising due to thin skin and age. Over time, after the dosage was bumped, the same developed to a lesser degree on my left shin and lower leg. As of about 10 days ago it had become plug ugly, gotten redder and purplier and spread. Bits of skin have peeled off leaving shine and not much else. My mother had a history of varicose veins but I do not. It could well be something vascular but, having stopped Metformin 10 days ago the area is now mildly improved, less redness and tenderness to touch. There is no deep pain or shortness of breath (DVT hallmarks) and the fact that there is improvement while off Metformin leads me to believe I may be having a reaction to it, and not in a good way. When I see my doctor tomorrow I am going to propose staying off Metformin until my regularly scheduled visit in 8 weeks. Clearly, if whatever this is comes roaring back or otherwise deteriorates she will be getting another call. If it clears, I'm done with it. I have lost 30 pounds in 15 months (another 75-90 to go, for my own personal goal) and track my foods and exercise daily. Fortunately the heat is finally over for the year and I can go back to walking a lot more and burn off more weight.
Anybody else have a similar derm reaction? scottie, ask your physician and the physicians. The bruising sounds like your liver and clotting factors to me. (I can be wrong)
The liver plays a role in the production of clotting factors as well as red blood cell production. Some of the proteins synthesized by the liver include coagulation factors I (fibrinogen), II (prothrombin), V, VII, VIII, IX, X, XI, XIII, as well as protein C, protein S and antithrombin. en.wikipedia.org/wiki/Liver
Peppy - clotting factors are fine - had a test within the past year because a blood relative (no pun intended) had issues so all siblings and close relatives were recommended to have this checked. Everything normal there. My liver function tests have been normal, mid-range results for years, checked every 6 months. I'm due in November for the next battery (complete metabolic panel, vitamin deficiency levels, thyroid, glucose of course, lipids). |
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Post by mnholdem on Sept 22, 2016 20:03:00 GMT -5
Thanks for the reply Aged. And Sophie, I saw that article when it came out. We are going up against cost, storage requirements and ease of use when trying to bump Metformin. I just can't shake the comments Al made about the product way back when. Monomers seem to signal the liver, but it has never been thoroughly evaluated specifically for that effect, as far as I know. The "Paradigm Shift" is a lot harder to make in the face of these cost and ease of use issues. I know bloodletting was very popular for centuries. I'm always going to be in Mannkind's corner. I know just enough science to make Afrezza seem like it should be a no-brainer to BP and insurance companies. Almost every week, I take x-rays on infected diabetic foot ulcers to check for boney involvement. Current treatments are failing. It seems at times that I've posted these about a hundred times, but with the influx of new members to ProBoards-MNKD over the past few months, it may be worth posting a few of these links again:
Short-term intensive insulin therapy at diagnosis in type 2 diabetes: plan for filling the gaps Link: onlinelibrary.wiley.com/doi/10.1002/dmrr.2603/full
Clinical Evidence for the Earlier Initiation of Insulin Therapy in Type 2 Diabetes Link: www.ncbi.nlm.nih.gov/pmc/articles/PMC3757533/
An Exclusive Interview with Al Mann, Founder and CEO, Mannkind Corp. Link: www.diabetesincontrol.com/an-exclusive-interview-with-al-mann-founder-and-ceo-mannkind-corp/
Blood Sugar 101: What They Don't Tell You About Diabetes Link: mnkd.proboards.com/thread/3407/blood-sugar-101-tell-diabetes
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The difficulty with disruptive medicine is that published benefits often appear to be "too good to believe". Unfortunately, that can be what some physicians, clinicians and academics will initially think about Afrezza, as they already do about remission of diabetes mellitus following early intensive insulin therapy (first link above). Nearly half the patients remained in drug-free remission after a year. Why isn't the snubbing of these STII studies by the ADA front page news?
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