https://dom-pubs.pericles-prod.literatumonline.com/doi/10.1111/dom.16647
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It depends a lot on how the study is done. Obese people might benefit but others do not: No association between metformin initiation and incident dementia in older adults newly diagnosed with diabetes 2023
And even in obese people, GLP-1RAs do better than metformin:
- Associations of semaglutide with Alzheimer’s disease-related dementias in patients with type 2 diabetes: A real-world target trial emulation study 2025
- Associations of semaglutide with first-time diagnosis of Alzheimer’s disease in patients with type 2 diabetes: Target trial emulation using nationwide real-world data in the US 2024
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Thanks
The other difference above might be that Metformin can help prevent (as in the study Aging Doc) posted vs cannot reverse (or slow) AD once it has gotten going?
The paper concludes “The utility of metformin to prevent dementia was not supported.” so I don’t think metformin can prevent dementia. And if it does it’s probably a weak effect, certainly weaker than SGLT2i and GLP-1RAs (and their combination?).
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I found it interesting that he had energy markers, what are these?
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To be honest it is typical for him. He provides values, but does not explain what the units are. (Obviously percentages don’t have units, but they are percentages of something).
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Kobe University endocrinologist Ogawa Wataru says, "It is known that diabetes patients experience changes in the blood levels of metals such as copper, iron and zinc.
"In addition, chemical studies found that metformin has the ability to bind certain metals, such as copper, and recent studies showed that it is this binding ability that might be responsible for some of the drug’s beneficial effects. So, we wanted to know whether metformin actually affects blood metal levels in humans, which had not been clarified.
In the journal BMJ Open Diabetes Research & Care , the Kobe University team has published the first clinical evidence of altered blood metal levels in patients taking metformin. They showed that drug-taking patients have significantly lower copper and iron levels and heightened zinc levels.
Association of metformin treatment with changes in metal dynamics in individuals with type 2 diabetes,
BMJ Open Diabetes Research & Care (2025).
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An interesting idea to cycle metformin
Metformin is one of the strongest AMPK activators - but only when used in the right context.
If you take it in a pulsed way and pair it with the right dietary signals (low glucose/low insulin window, mild caloric deficit, fasted zone 1/2, etc.), it can really show its value, amplifying AMPK cascade.
What many people expect is a “magic pill” you take every day and it fixes everything. But biology doesn’t work like that - continuous daily dosing can blunt the metabolic signal and even interfere with adaptations.
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This seems similar to the research that came out years ago. It’s why I avoid it generally…
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I also avoid it because it’s hard on kidneys - otherwise I would take it.
It appears that Metformin crosses the BBB and directly affects the brain.
After 60 Years, Diabetes Drug Found to Unexpectedly Affect The Brain : ScienceAlert
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I have a general question about SGLT2i, metformin, and Lipid lowering meds (Ezetimibe, PITA, etc). Is it a ok to take them every other day as opposed to daily? or maybe anywhere from 2-3 days per week or they must be taken daily? I am talking for those of us that take them for longevity purposes only and have our markers in the normal/optimal range.
Reason I ask is because I do trial and error sometimes (especially if I’m feeling not my best, I just stop everything/most meds for 2-4 days) and then I feel great. and that great feeling tends to stay with me even when I start taking meds again for a while, say two weeks or so. Now, I’m not necessarily blaming meds for the time I may not be feeling best (could be other things also, i.e. lack of sleep, weather, cold symptoms etc…)
Has anyone come across research or suggestions (from the longevity docs) that might be a good idea to take these meds more sparingly as opposed to daily?
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If you’re doing trial and error to find out what works for you, you’re better off taking something for a block of time and then not taking it for a block of time and noting differences. Repeat it a few times and you’ll see what is working and what is not.
You absolutely can take things on and off. I take SGTL2i 4 days in a row and take a 3 day break. This is to prevent urinary infection and excess urination (I find that annoying).
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