1. Cardiopulmonary function improvement reduced by 40%-60%
Cardiopulmonary function (measured by peak oxygen uptake, VO₂peak) is one of the strongest predictors of all-cause and cardiovascular mortality. Studies have found that the VO₂peak in the exercise-only group increased by an average of about 2.5–3 ml/kg/min, while the exercise + metformin group only increased by about 1.3–1.8 ml/kg/min.
The average difference between the two reached -1.19 ml/kg/min (95% CI: -2.33 to -0.04), which means that metformin directly reduced the cardiopulmonary benefits of exercise by 40%–60%.
Do not underestimate the difference of this 1 ml/kg/min. Existing studies have confirmed that for every 1 ml/kg/min increase in VO₂peak, all-cause mortality decreases by approximately 10%–15%.
2. Blood pressure improvement effect is greatly reduced
Another important benefit of exercise is lowering blood pressure, which is also key to preventing cardiovascular events such as heart attacks and strokes. The study found:
The average systolic blood pressure in the exercise-only group decreased by about 7–8 mmHg.
The exercise + metformin group only decreased by about 3–4 mmHg.
The difference between the two reached 3.76 mmHg (95% CI: 0.63–6.89).
Diastolic blood pressure also showed a similar trend: the exercise-only group decreased by an average of about 4 mmHg, while the combination group only decreased by about 2 mmHg, with a difference of 1.98 mmHg (95% CI: 0.42–3.55).
Similarly, the clinical significance of this numerical difference should not be underestimated. For every 5 mmHg reduction in systolic blood pressure, the risk of major cardiovascular events is reduced by about 10%. Metformin is equivalent to cutting the blood pressure-lowering effect of exercise in half.
we just don’t know how long the pathways through which metformin blunts exercise benefits actually remain affected. Many drugs can have effects that last long after they’ve been cleared from the bloodstream.
My thought on metformin is that it is a good drug for people that don’t exercise. Some of the stress it induces seems like an exercise mimetic. Actual exercise is better.
It isn’t that simple but if you have to ask the question of how to time exercise and metformin, you are probably better off not taking it.
Unless you’re diabetic, what advantage is there in taking metformin? No convincing studies in human nondiabetics show benefits. If you’re prediabetic, studies show lifestyle interventions (including diet and exercise) are significantly superior to metformin in increasing insulin sensitivity and preventing or slowing progression to diabetes. For weight control diet is superior. Anyone interested in life/health extension will already have better diet, exercise and weight control, again rendering metformin less desirable, especially vs exercise. For additional glucose control SGLT2i are safer and afford pleiotropic benefits while affecting exercise much less (more exotic: acarbose and imeglimin). If diabetic there may be reasons to take metformin.
It is a very inexpensive weight loss drug - that is one reason and you can’t say diet works better. I mean you can but that isn’t the proper comparison. Diet + Metformin works better than diet alone. Lots of even better options but none are $5 a month.
It isn’t fair for any lifestyle mods to say they work better than metformin say for pre diabetes progression either. If lifestyle+ metformin work better than lifestyle alone, that matters. I honestly don’t know if that is true. Only that lifestyle mods work better but not sure if metformin adds anything to that.
I suspect no one has done the study on people who can’t or won’t exercise and compared diet alone to diet + metformin for diabetes progression. I have a feeling metformin would offer a benefit. But that is just a feeling not data.