Looking into it now…

I found this quote in a 2015 article (Pryor, Rosina, and Filipe Cabreiro. “Repurposing metformin: an old drug with new tricks in its binding pockets.” Biochemical Journal 471.3 (2015): 307-322.):

Given the wide-ranging effects of metformin in host physiology, which includes alteration of body weight, temperature, normalization of serum glucose, insulin, triglycerides and cholesterol levels, regulation of oestrous function and anti-neoplastic effects, confounders are likely to occur and influence lifespan trials with biguanides and therefore need careful consideration. In a recent study by Martin-Montalvo et al. [Martin-Montalvo, Alejandro, et al. “Metformin improves healthspan and lifespan in mice.” Nature communications 4.1 (2013): 1-9.], the calorie restriction mimicking effects of metformin could be the underlying mechanism responsible for the effects the drug on lifespan and healthspan. These include improved fitness, increased insulin sensitivity and reduced low-density lipoprotein and cholesterol levels without a decrease in caloric intake. At the molecular level, metformin alters gene expression similarly to that observed on calorie restriction. Interestingly, metformin increases AMPK activity without concomitant activity changes in the respiratory chain. It activates an antioxidant and anti-inflammatory response leading to reductions in both oxidative damage accumulation and chronic inflammation.

Altogether, the collected data existing from several model organisms show a promising outlook for the potential benefits of using metformin as an anti-aging strategy. However, further investigations are required for its use in humans as its definite anti-aging mechanism is still not fully disclosed.

But it is 2022, so we might know a bit more by now. This is the most recent review I could find:

Chen, Sheng, et al. “Metformin in aging and aging-related diseases: clinical applications and relevant mechanisms.” Theranostics 12.6 (2022): 2722.

Aha… I refer you to Figure 4 in that review (“Multiple pathways of metformin targeting aging and aging-related diseases”), it appears that the current understanding is that metformin affects aging via multiple different pathways. In some of these pathways its effect is rather direct - for example, it acts as an inhibitor of the mitochondrial respiratory-chain complex 1. Looking at this makes me believe that it does have direct physiological effect and does not only act indirectly via its effects on calorie restriction. I don’t know much on the topic, I only know how to scan quickly though the literature, so I am not really able to tell you how similar the effects are to those of a calorie deficit.

I take it daily. How it works is not the critical issue for me, it is all the data suggesting it works with apparently few adverse consequences.

So I figure, what do I have to lose.