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.