Metformin is the 3rd most prescribed drug in the US. It’s massively common among type 2 diabetics as that was what it was designed for.
However, like some other compounds in the longevity space - many people have found uses for metformin outside of the original prescribed use. This is called off-label use and one of the primary uses of this has become metformin for weight loss.
But before we get into that - let’s back up.
What Is Metformin?
Metformin was originally a drug (the first mainstream one) for the treatment of type 2 diabetes.
While originally exclusively prescribed for type 2 diabetic patients - it’s gained interest in the longevity communities around weight loss and has some use for women dealing with PCOS.
Metformin: Mechanism fo rAction
Metformin seems to work by stressing the mitochondria and stressing it. Similarly to stressing your muscles, this forces the mitochondria to break down and rebuild it self stronger.
Metformin also seems to have effects in increasing AMPK levels (a protein associated with healthy metabolism effects), improved gut microbiome, and other important metabolic pathways.
Prescribed Metformin Usage
Metformin is typically prescribed for type 2 diabetics to help reign in their glucose sensitivity. This has been the primary usage of metformin over the years and the reason why it’s the #3 prescribed drug in the US.
However, over the years - many people have noted the effects that this can have on type 2 diabetic and obesity and have started to experiment this in otherwise healthy populations for weight loss and longevity.
Metformin dosage for weight loss
On-label use of metformin usually starts at 500mg every 12 hours or so (1000mg/day) working up to 1500-2550mg/day. Typically users max out at 2550mg/day.
Metformin: Timing of Dosage
David Sinclair uses metformin before bedtime - proposing that it may accelerate the fasting state and improve that entire process.
However, in most medical situations - metformin is prescribed alongside meal times - presumably to help nullify the effect of glucose spikes that you may have during meals.
Metformin for Non-Diabetics
When used in focusing on preventing type 2 diabetes in non-diabetics - and losing weight - typically the dosage is around 850mg/day.
Metformin is also used by women to help treat PCOS - it does this by the same mechanistic route by improving the body’s sensitivity to insulin - therefore decreasing the level of circulating insulin and thereby turning off the signaling for the body to store fat.
This is typically used for women with a higher BMI, but the response seems to actually be best in women whop already have a lower BMI when treatment starts.
Metformin Side Effects
Metformin seems to be relatively well tolerated in most populations. However, similar to other supplements or medications, it has some common side effects which may vary person to person. These include nausea, sickness, indigestion, loss of appetite. GI distress seems to be the most common symptom across the board.
A more alarming side effect may be a metallic taste in your mouth. Considering you should talk to a doctor beforehand, if you experience nay of these - you should definitely check back in.
The most significant side effect can be lactic acidosis. This is where your body is unable to clear lactic acid quickly enough. This can be life threatening and is most common in patients who already have a kidney disease. Talk to your doctor if you have kidney concerns. There is some controversy over whether or not this is actually a concern - especially in recent studies.
Other rare side effects include, change of awareness, difficulty concentrating, loss of strength, poor sleep or frequent tiredness.
Metformin Side Effects for Women
The side effect profile for women seems to be the same as men (as far as we know to date). Therefore, be careful if using for PCOS and be sure to evaluate your usage regularly with your doctor.
Metformin Long Term Side Effects
Metformin does not seem to have (so far) any long term side effects. There may be a chance of depleting vitamin b12 over time - so make sure you get those levels checked on a regular basis.
There is some concern that metformin may increase the chances of a birth defect by up to 2% - but this was a single study and needs to be replicated.
Metformin, the type 2 diabetes drug taken to slow aging, may increase the chances of a birth defect in offspring by 1.9%. So before conceiving a child, men should talk to their doctor about stopping metformin at least 3 months earlier https://t.co/ElkzxM5CGe— David Sinclair (@davidasinclair) April 10, 2022
Because Metformin has interactions with other dugs, you should talk with your doctor before taking it.
Other Drugs Sometimes Used with Metformin
There are some combinations of prescriptions that are often utilized together.
Metformin and Ozempic
Metformin and Ozempic are often used together for type 2 diabetes and weight loss. They work different though.
Ozempic is primarily administered via injection (once a week) and used to slow down digestion, stimulate insulin release and lower the amount of glucose your body produces.
While this is often used in conjunction with metformin for type 2 diabetics - people who are using metformin for weight loss typically do not use Ozempic at the same time.
Metformin on Podcasts
David Sinclair has popularized Metformin more than anyone. Here's the recent mention on his podcast #4
We’ll be researching and sharing more metformin studies over time including:
- Metformin alleviating neurocognitive aging effects.
- Metformin effect on testosterone.
- Metformin on epigenetic age of patients
Other Research Guides
Other guides you may want to investigate