Metformin and Weight-Loss?

If you have diabetes, you very likely have heard of metformin, or if you have been paying attention to the news in the last couple of years, you may have also heard of it being recalled. Now I am not here to talk about how bad metformin is; actually, quite the opposite! Instead, today we are talking about why some people might lose weight when taking metformin. 

I heard it was recalled; fact or crap? 

First off, the reason metformin was recalled is not because of the drug itself. It was recalled as large batches of the drug from multiple manufacturers were found to be contaminated with a possible carcinogen. These drugs are continually tested for quality control, so this contaminate was found during recent testing; therefore, it hasn’t been around for any extended period of time. So if you happened to be taking some metformin that was recalled, there is likely no concern as the concentrations of a possible carcinogen was relatively low. Further, as a ‘possible’ carcinogen, that does not mean it will be carcinogenic for every single person or living organism that comes into contact with it. If you have concerns though, please follow up with your care provider! 

So Metformin is good to use? 

Ok, on to the good stuff. Metformin belongs to a class of medications called biguanides. Metformin is the most widely prescribed medication for diabetes and one of the most commonly prescribed medications globally. That is because it is hella good at what it does, like I mean real hella good! It has been around since the 1950s, and we have a mountain of data on its safety and efficacy. The more we research it, the more we find further benefits – everything from antiaging, protecting your brain and heart, to managing Polycystic Ovarian Syndrome (PCOS). So an argument could be made that everyone should take this medication for the benefits outside of managing blood sugars in diabetes! 

And for my haters, no, I am not paid by big pharma; I wish. My massive student loan debt would happily accept a payout at this point! But unfortunately, no one is making money on metformin anymore. In some respects, it costs more to manufacture the tablets than what they are currently sold for, even in the states where the price of drugs is ridiculous.

Anywho, Metformin and weight-loss! 

Ok, wait; what does Metformin actually do? 

Metformin’s primary mechanism of action is by reducing insulin resistance. Thereby, what insulin your body does produce is more effective at lowering your blood sugar levels. However, it has also been found that metformin seems to increase two other hormones in the body called GLP-1 and GDF15. GLP-1 (you will know if you have been following me for a while) is the molecule found in our current obesity medications called Ozempic/Wegovy and Saxenda. So we already know the GLP-1 can help with weight management by reducing your wanting and food-seeking behaviours. 

And what about GDF15?

A recent paper found that metformin increases the hormone GDF15 or growth/differentiation factor 15, which we know is a satiety hormone. The increase in GDF15 levels was modestly correlated with weight-loss, and participants taking metformin lost ~3.5% of their baseline body weight compared to the placebo group. 

Now we don’t know all the ins and outs of how exactly GDF15 can lead to weight-loss, but it seems to act at a brain-stem-restricted receptor which helps to reduce appetite and body weight. Pretty cool, right? 

Now this effect on GDF15 is NOT going to be experienced by everybody! However, some individuals using metformin for diabetes will and have likely enjoyed this benefit. 

So, ask my doc for Metformin for weight-loss? Great!

I need to mention that metformin is not currently used solely for obesity or weight management. While it does have some evidence, and you might find some doctors out there prescribing it for weight, anti-aging, etc., in these situations, it is considered off-label as metformin does not have the indication from the FDA or Health Canada for Obesity management. So it would be prescribed in a gray area which comes with potential risks if something goes wrong for the prescribing clinician. Furthermore, the potential weight-loss benefit from Metformin is not exactly stellar compared to the other obesity agents that are currently out there. For example, in the study I mentioned above, participants on Metformin only lost 3.5% of their baseline body weight. Generally, we aim for a weight-loss of at least 5% or more! 

So unless you have diabetes, PCOS, or another extenuating circumstance where metformin may be beneficial, your family physician is unlikely to prescribe it. Perhaps a specialist has more expertise and may be comfortable with it. Will this change in the future? Perhaps but for now, if weight management is our only consideration, we have other options that are much more effective! 

A final thought from Dr. Dan

As I already expect, there will be a million comments about how metformin destroys your kidneys and liver etc. There is no evidence to show this; in fact, metformin has been shown to protect the kidneys, heart and liver. Does metformin have potential GI side effects? Yes, absolutely, and for some, it will be intolerable. In rare extenuating circumstances, can metformin cause a condition called Lactic Acidosis which could affect your kidneys? Yes. However, this condition is exceedingly rare. This side effect was seen more frequently with a sister molecule called phenformin which was pulled from the market long ago. It is still something we need to monitor, but overall, metformin is exceedingly safe for a vast majority of people, which comes from 70+ years of data.

So metformin is a fascinating little molecule that is very effective at what it does in terms of blood sugar management. For some, it might have the added benefit of leading to weight loss! As time goes on, I am sure we will learn more about the potential benefits of this medication! 

That is all for today, folks. If you have any questions, please feel free to reach out, and until next time remember, small tweaks lead to massive peaks. 

– Dr. Dan 

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