|
Post by mango on Jun 6, 2018 0:48:29 GMT -5
good work. Afrezza. 7.98% - 7.77% = .21 Hba1c which is measured in %. Novolog 7.88% - 7.48% = .40 hbA1c which is measured in %. Mango at work, interesting point. My take on the 0.21 vs 0.4% thing is first of all who was studied? This trial wasn't as if we were looking at insulin naive patients. And this is essential to keep in mind. They were already taking something. Why would they improve in the rapid acting group by 0.4%? That was the sophisticated protocols and monitoring/ titration by experts. Read more: mnkd.proboards.com/thread/49/red-acre-mnkd-8-18#ixzz5HcRfyCKjThe Gen2 arm of the trial was non-inferior to Insulin Aspart in terms of change in HbA1c over the treatment period (-0.21 % vs -0.4%). Afrezza patients had fewer hypos than Aspart users (9.8 per subject-month vs 13.97 per subject-month)Afrezza patients lost weight while Aspart patients gained weight Fewer patients in the Afrezza arm achieved treatment goals of HbA1c < 7% or 6.5% compared to Aspart, this difference was statistically significant Read more: mnkd.proboards.com/thread/49/red-acre-mnkd-8-18#ixzz5HcLx8faQThis looks more clinically significant: Afrezza patients had fewer hypos than Aspart users (9.8 per subject-month vs 13.97 per subject-month) HbA1c is a proxy for average glucose and does not reflect glucose homeostasis. A single hypo can cause a dramatic reduction in an HbA1c value. Affinity 1, peppy what do you see? I think I can see a significant improvement in fasting blood glucose which means glucose homeostasis is being restored.
|
|
|
Post by peppy on Jun 6, 2018 0:52:40 GMT -5
Mango at work, interesting point. My take on the 0.21 vs 0.4% thing is first of all who was studied? This trial wasn't as if we were looking at insulin naive patients. And this is essential to keep in mind. They were already taking something. Why would they improve in the rapid acting group by 0.4%? That was the sophisticated protocols and monitoring/ titration by experts. Read more: mnkd.proboards.com/thread/49/red-acre-mnkd-8-18#ixzz5HcRfyCKjThe Gen2 arm of the trial was non-inferior to Insulin Aspart in terms of change in HbA1c over the treatment period (-0.21 % vs -0.4%). Afrezza patients had fewer hypos than Aspart users (9.8 per subject-month vs 13.97 per subject-month)Afrezza patients lost weight while Aspart patients gained weight Fewer patients in the Afrezza arm achieved treatment goals of HbA1c < 7% or 6.5% compared to Aspart, this difference was statistically significant Read more: mnkd.proboards.com/thread/49/red-acre-mnkd-8-18#ixzz5HcLx8faQThis looks more clinically significant: Afrezza patients had fewer hypos than Aspart users (9.8 per subject-month vs 13.97 per subject-month) HbA1c is a proxy for average glucose and does not reflect glucose homeostasis. A single hypo can cause a dramatic reduction in an HbA1c value. Affinity 1, what do you see? I see hypoglycemia. 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%). I see the numerator and denominator? Absolute value? (I am a stinker)
|
|
|
Post by mango on Jun 6, 2018 1:21:28 GMT -5
|
|
|
Post by peppy on Jun 6, 2018 1:37:21 GMT -5
HbA1c is a proxy for average glucose and does not reflect glucose homeostasis. A single hypo can cause a dramatic reduction in an HbA1c value. Affinity 1, what do you see? I see hypoglycemia. 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%). I see the numerator and denominator? Absolute value? (I am a stinker) 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.pdfIn 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. Se- vere hypoglycemia may be recognized or unrecognized and can progress to loss of consciousness, seizure, coma, or death. It is reversed by administration of rapid-acting glucose or glucagon. Clinically significant hypoglycemia can cause acute harm to the person with diabetes or others, espe- cially if it causes falls, motor vehicle acci- dents, or other injury. A large cohort study suggested that among older adults with type 2 diabetes, a history of severe hypo- glycemia was associated with greater risk of dementia (77). Conversely, in a sub- study of the ACCORD trial, cognitive impairment at baseline or decline in cog- nitive function during the trial was sig- nificantly associated with subsequent episodes of severe hypoglycemia (78). Ev- idence from DCCT/EDIC, which involved adolescents and younger adults with type 1 diabetes, found no association be- tween frequency of severe hypoglycemia and cognitive decline (79), as discussed in Section 12 “Children and Adolescents.”
Severe hypoglycemia was associated with mortality in participants in both the standard and the intensive glycemia arms of the ACCORD trial, but the relationships between hypoglycemia, achieved A1C, and treatment intensity were not straight- forward. An association of severe hypo- glycemia with mortality was also found in the ADVANCE trial (80). An association between self-reported severe hypoglyce- mia and 5-year mortality has also been reported in clinical practice (81).* another numerator and denominator for absolute value?
|
|
|
Post by peppy on Jun 6, 2018 2:00:34 GMT -5
Absolute terms, the terms prior to the %. Absolute terms show the numerator and denominator. SHOW YOUR WORK>www.youtube.com/watch?v=rcHQElKhWFcH Gilbert Welch - The Two Most Misleading Numbers in Medicine Love you. Here you go 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. aged can you calculate the absolute value on this data please? 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%).
|
|
|
Post by peppy on Jun 6, 2018 2:16:44 GMT -5
|
|
|
Post by mango on Jun 6, 2018 2:43:53 GMT -5
|
|
|
Post by sayhey24 on Jun 6, 2018 5:17:37 GMT -5
DBC - Now thats funny "I don't think they'll be any other use of CGMs with TI other than this and 162. Most of the MNKD trials were before CGMs where widely available" The CGM was available to Al before Technosphere Insulin was invented. Al invented the CGM. www.sharecare.com/health/diabetes/when-was-cgm-introducedAl did not invest a $B willy-nilly. He tested everything. The HUGE mistake Al made was letting people know it was insulin. Insulin has a bad rap. Nobody wants insulin. Its dangerous. Its needles. Its a mess. He should have told people it was a new anti-glycemic amino acid class and never used the word insulin. Mike has a marketing problem not a product problem. Dr. Kendall has all the studies to show this. Mike has to re-invent afrezza as an anti-glycemic and stop getting people to think about it as insulin.
|
|
|
Post by sayhey24 on Jun 6, 2018 5:23:47 GMT -5
|
|
|
Post by brotherm1 on Jun 6, 2018 6:46:48 GMT -5
The Gen2 arm of the trial was non-inferior to Insulin Aspart in terms of change in HbA1c over the treatment period (-0.21 % vs -0.4%).Afrezza patients had fewer hypos than Aspart users (9.8 per subject-month vs 13.97 per subject-month)Afrezza patients lost weight while Aspart patients gained weightFewer patients in the Afrezza arm achieved treatment goals of HbA1c < 7% or 6.5% compared to Aspart, this difference was statistically significant
Read more: mnkd.proboards.com/thread/49/red-acre-mnkd-8-18#ixzz5HcLx8faQ===================================================================== mango the above post by you part of the gold necklace? you are digging up the old work? heh ==================================================================== 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 diabetesed.net/wp-content/uploads/2017/12/2018-ADA-Standards-of-Care.pdf“Fewer patients in the Afrezza arm achieved treatment goals of HbA1c < 7% or 6.5% compared to Aspart, this difference was statistically significant” Is this perhaps what digger was referring to when he said MNKD needs to do a study to show Afrezza can do a better job of lowering HbA1c so we can get better insurance coverage?
|
|
|
Post by peppy on Jun 6, 2018 7:41:44 GMT -5
The Gen2 arm of the trial was non-inferior to Insulin Aspart in terms of change in HbA1c over the treatment period (-0.21 % vs -0.4%).Afrezza patients had fewer hypos than Aspart users (9.8 per subject-month vs 13.97 per subject-month)Afrezza patients lost weight while Aspart patients gained weightFewer patients in the Afrezza arm achieved treatment goals of HbA1c < 7% or 6.5% compared to Aspart, this difference was statistically significant
Read more: mnkd.proboards.com/thread/49/red-acre-mnkd-8-18#ixzz5HcLx8faQ===================================================================== mango the above post by you part of the gold necklace? you are digging up the old work? heh ==================================================================== 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 diabetesed.net/wp-content/uploads/2017/12/2018-ADA-Standards-of-Care.pdf“ Fewer patients in the Afrezza arm achieved treatment goals of HbA1c < 7% or 6.5% compared to Aspart, this difference was statistically significant”Is this perhaps what digger was referring to when he said MNKD needs to do a study to show Afrezza can do a better job of lowering HbA1c so we can get better insurance coverage? Insulin Aspart in terms of change in HbA1c over the treatment period (-0.21 % vs -0.4%). Afrezza patients had fewer hypos than Aspart users (9.8 per subject-month vs 13.97 per subject-month) Brothern, look closer at the clinical significance. It took 14 hypos per subject a month on Aspart in order to get the -0.4 change in hbA1c from 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. look at it this way, it took 14 hypoglycemic events a month for Novolog to lower hbA1c 0.4 from 7.88% to 7.48%. The ADA saying to increase hbA1c target to avoid Hypos.
|
|
|
Post by peppy on Jun 6, 2018 8:26:34 GMT -5
- 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 diabetesed.net/wp-content/uploads/2017/12/2018-ADA-Standards-of-Care.pdfWith any luck, what dr Kendall is going to do, is use the guidelines as is to make afrezza the standard of care. Less Hypos, glycemic control.
|
|
|
Post by akemp3000 on Jun 6, 2018 8:45:06 GMT -5
Agreed. Dr. Kendall will use data as opposed to luck to make Afrezza the standard of care but knowing the opposition from BPs that will certainly come will require both luck and some level of integrity from industry decision makers.
|
|
|
Post by peppy on Jun 6, 2018 9:03:10 GMT -5
Agreed. Dr. Kendall will use data as opposed to luck to make Afrezza the standard of care but knowing the opposition from BPs that will certainly come will require both luck and some level of integrity from industry decision makers. as has been pointed out, the rules are the rules. Here is the killer, not sure I can dig it up. On my reading last night, it was in the standards of care, had to be, The RAA's were approved non inferior to NPH. Afrezza made from regular insulin/ NPH. NPH Human Insulin which has an onset of insulin effect of 1 to 2 hours, a peak effect of 4 to 6 hours, and duration of action of more than 12 hours. ... Pre-Mixed Insulin which is NPH pre-mixed with either regular human insulin or a rapid- acting insulin analog.
|
|
|
Post by agedhippie on Jun 6, 2018 9:13:05 GMT -5
linkFollowing which Mannkind had to publish a retraction ( link) and reissue the press release - the results were not statistically significant: CORRECTING and REPLACING MannKind Reports Positive Data from a Phase 3 Clinical Study of AFREZZA in Patients with Type 1 Diabetes
CORRECTING and REPLACING MannKind Reports Positive Data from a Phase 3 Clinical Study of AFREZZA in Patients with Type 1 DiabetesVALENCIA, Calif.--(BUSINESS WIRE)--Aug. 14, 2013-- Second graph under Other Results subhead, second sentence should read: The event rate of severe hypoglycemia was also lower in the AFREZZA-Gen2 group (8.05 events per 100 subject-months) than in the insulin aspart group (14.45 events per 100 subject-months); however, this difference was not statistically significant (p=0.1022) (sted The event rate of severe hypoglycemia was also lower in the AFREZZA-Gen2 group (8.05 events per subject-month) than in the insulin aspart group (14.45 events per subject-month); however, this difference was not statistically significant (p=0.1022)).Then there was the whole corrected release under that but I will spare people that.
|
|