Eddy Edson
Well-Known Member
- Relationship to Diabetes
- Type 2
... for T2D's.
New study:
And a discussion thread:
(Ozempic is currently the most widely known GLP-1R agonist.)
About 10% hazard reduction, which doesn't msound huge but is I think way bigger than anything else out there. None of the other "second line" T2D meds show a significant hazard reduction (question mark for SGLT-2 meds; not enough data).
The idle methodology question I have is to what extent HbA1c or other metabolic/CV markers may be confounders in this analysis, which doesn't adjust for them directly. In the commentary:
There are several potential mechanisms of action. For example, it is plausible that the effect of GLP-1 RAs on dementia could be related to amelioration of dementia-related risk factors, such as glycated hemoglobin, body weight, systolic blood pressure, and cardiovascular disease observed in the included RCTs.10-12 However, animal studies point to more general neuroprotective mechanisms of GLP-1 RAs,13 which could have implications for a broader patient population. The role of GLP-1 RAs in reducing neuroinflammation25, 26 may be important, given the recent focus on microglia in neurodegenerative diseases.27 It has been shown that semaglutide specifically decreases markers of systemic inflammation in patients,28, 29 and that both liraglutide and semaglutide attenuate development of atherosclerotic plaques in APOE–/– and LDLr–/– mice through an anti-inflammatory mechanism.30 A recent study showed that exenatide, another GLP-1 RA, improved brain vascular health in an aged mouse model in which transcriptome analysis showed enrichment for human AD genome-wide association study genes.31 In humans, it was recently demonstrated that liraglutide slowed down the decline in memory function independently of weight loss in a group of patients with obesity and prediabetes or early type 2 diabetes.32 Thus, in addition to its glucose-lowering effect, GLP-1 RAs may have specific properties for preventing dementia. This is supported by our finding from the nationwide cohort that other second-line diabetes treatments available were not associated with a lower incidence of dementia.
So the authors are pretty sure that the protective effect goes beyond what would be due to improved HbA1c etc etc, but obviously would be good to see that addressed more directly.
New study:
And a discussion thread:
(Ozempic is currently the most widely known GLP-1R agonist.)
About 10% hazard reduction, which doesn't msound huge but is I think way bigger than anything else out there. None of the other "second line" T2D meds show a significant hazard reduction (question mark for SGLT-2 meds; not enough data).
The idle methodology question I have is to what extent HbA1c or other metabolic/CV markers may be confounders in this analysis, which doesn't adjust for them directly. In the commentary:
There are several potential mechanisms of action. For example, it is plausible that the effect of GLP-1 RAs on dementia could be related to amelioration of dementia-related risk factors, such as glycated hemoglobin, body weight, systolic blood pressure, and cardiovascular disease observed in the included RCTs.10-12 However, animal studies point to more general neuroprotective mechanisms of GLP-1 RAs,13 which could have implications for a broader patient population. The role of GLP-1 RAs in reducing neuroinflammation25, 26 may be important, given the recent focus on microglia in neurodegenerative diseases.27 It has been shown that semaglutide specifically decreases markers of systemic inflammation in patients,28, 29 and that both liraglutide and semaglutide attenuate development of atherosclerotic plaques in APOE–/– and LDLr–/– mice through an anti-inflammatory mechanism.30 A recent study showed that exenatide, another GLP-1 RA, improved brain vascular health in an aged mouse model in which transcriptome analysis showed enrichment for human AD genome-wide association study genes.31 In humans, it was recently demonstrated that liraglutide slowed down the decline in memory function independently of weight loss in a group of patients with obesity and prediabetes or early type 2 diabetes.32 Thus, in addition to its glucose-lowering effect, GLP-1 RAs may have specific properties for preventing dementia. This is supported by our finding from the nationwide cohort that other second-line diabetes treatments available were not associated with a lower incidence of dementia.
So the authors are pretty sure that the protective effect goes beyond what would be due to improved HbA1c etc etc, but obviously would be good to see that addressed more directly.