I was waiting for someone else to answer since I have only been taking metformin since October 2019. I take 2000 mg daily - half in the morning and half at night. I am 68 years old and working on losing weight (most recently was 188 pounds with a goal of 150 pounds). I am not diabetic per fasting glucose (92) or HbA1c (5.3) but my glucose spikes up to 140 after meals (I don't eat anything with added sugar, no highly processed products, no white floor, no rice, nothing with white flour, etc.) My wife and I are in SE Asia for 5 months and since metformin is over the counter here, I get to decide.
Here are some reference that I found before I decided how much to take:
Targeting Aging with Metformin (TAME) study
Dose: 850 mg 2x per day
Bill Faloon - Founder of Life Extension
Dose: high dose (850 mg) of metformin two to three times a day (his personal dose)
Dr. Sandra Kaufmann, author Kaufmann Protocol - Why We Age and How to Stop It
Dose: 500 mg to 2000 mg metformin daily
Dr. David Sinclair, author of Lifespan: While We Age and Why We Don’t Have To
Dose: 1000 mg metformin daily (his personal dose - he takes it all in the evening)
Reference: In the Conclusion chapter of his book
Both Dr. Kaufmann, who is a MD, and Dr. Sinclair, who is not a MD, discuss AMPK and MTOR in reference to metformin.
Note: I find Dr. Kaufmann's and Dr. Sinclair's book secondary titles interesting. The titles both say that if you do what is in their book, you won't age anymore. I don't believe that the titles are completely accurate at this point - even for mice much less humans.
As David has noted there are doses recommended, and I suspect these doses are all based on the standard doses for diabetes. I doubt any studies have been done comparing various doses and their impact on mTOR. As far as I know, the TAME study is the first human study. If you go to the fight aging website, they will argue that the risks outweigh the benefits with metformin. Good luck to you.
Usual Adult Dose for Diabetes Type 2
Immediate-release: Initial dose: 500 mg orally twice a day or 850 mg orally once a day -Dose titration: Increase in 500 mg increments weekly or 850 mg every 2 weeks as tolerated
Maintenance dose: 2000 mg/day in divided doses Maximum dose: 2550 mg/day
-Immediate-release: Take in divided doses 2 to 3 times a day with meals; titrate slowly to minimis gastrointestinal side effects. In general, significant responses are not observed with doses less than 1500 mg/day and doses above 2000 mg are generally associated with little additional efficacy and poorer tolerability.
10 Big Myths About Metformin, the Popular Diabetes Drug
(Note I removed the text for these 10 myths except for the first two.:
1) Metformin is bad for your kidneys.
It’s not. There may be some confusion here because up until 2016, patients with higher creatinine levels—a potential sign of kidney dysfunction—were advised not to take metformin. But metformin, in fact, does not cause kidney problems, and that recommendation has since changed. Now, labels for metformin say that only patients with late-stage chronic kidney disease (stage IV or V) should not use the medication.
2) Metformin is bad for your liver.
The truth is, in the vast majority of cases, it’s not. The liver isn’t involved in processing and metabolizing metformin at all. Instead, metformin leaves the body unchanged in the urine. Metformin could actually be beneficial to patients with certain liver diseases.
Still, liver injury due to metformin is a very rare, but possible, reaction. Patients who experience this reaction have usually used metformin for 4 to 8 weeks at the same time as using other medications that can damage the liver.
3) Metformin is dangerous to take during pregnancy.
4) Metformin causes dementia.
5) Metformin is bad for your heart.
6) Metformin causes scary lactic acidosis.
The risk of metformin causing lactic acidosis of the blood is exceedingly rare. A Cochrane systematic review of 70,490 patients with type 2 diabetes on metformin did not report a single case of metformin-induced lactic acidosis. The risk of metformin causing lactic acidosis appears to be no greater than that of non-metformin therapies.
7) Metformin raises cholesterol.
8) Metformin is bad for the pancreas.
9) Metformin causes cancer.
10) You can’t have a CT scan with contrast when taking metformin.