A study published in Obesity suggests that metformin may decrease the gains in cardiorespiratory performance brought on by exercise.
The world’s most common diabetes drug
Metabolic syndrome, which is represented by the four connected symptoms of obesity, excessive fats in the bloodstream (dyslipidemia), high blood pressure (hypertension), and excessive blood sugar (hyperglycemia), all of which are strongly related to diabetes . Metformin is the most prescribed drug in the world for hyperglycemia, as it has significant effects on nutrient sensing.
While metformin is also being explored as a longevity drug, particularly in the Targeting Aging with Metformin trial, it is clearly not perfect. At least some cohorts do not experience reduced mortality, it has been reported to reduce male fertility, and we have also reported on a previous study that evaluated metformin’s negative effects on muscle hypertrophy. While many of its effects were positive and even rejuvenating in certain ways, this drug can blunt certain gene expression pathways related to muscle growth.
Previous studies have shown that cardiorespiratory fitness, as defined by an increase in the oxygen uptake measurement VO2max, may have an impact in preventing hyperglycemia and type 2 diabetes, although the associated weight loss is also likely to contribute . The researchers of this study sought to determine if metformin impairs gains in VO2max the way it impairs muscle growth, as has been suggested by previous studies .
A cohort of its users
This study focused on the people most likely to be taking metformin: people with metabolic syndrome. A total of 72 overweight or obese men and women with an average age of 53 were separated based on whether they were taking metformin or not. 63 of these people were able to complete 16 weeks of high-intensity interval training (HIIT), which focuses on exercise sessions that maximize heart rate in order to increase cardiovascular and respiratory performance. Markers of metabolic syndrome, oxygen respiration, and blood glucose were assessed.
However, this was not a placebo-controlled study, and the baseline characteristics of the two groups were different. As expected, people in the metformin group had more glucose and more insulin resistance, and both groups were positively affected by HIIT in this respect. There were no significant differences in the amount of improvement on these measurements.
Both groups were also positively affected in every measurement of VO2max, but the researchers’ hypothesis was correct: the improvements brought on by HIIT in this respect were significantly blunted in people taking metformin. While there was no significant difference in baseline measurements, the people who did not metformin had superior cardiorespiratory performance to the people who did.
These results do not provide any basis for people to cease taking metformin, and they do not suggest some sort of unknown danger. As an inhibitor of blood glucose, metformin is prescribed for reasons that almost always outweigh the concerns raised in this study.
However, this study does illustrate an important potential problem with this drug, and it casts further shade on the idea that it may one day be employed as a broad longevity pill rather than a drug used to treat a specific condition. Like nearly every other prescription drug, metformin is almost certainly a double-edged sword, with positive effects and significant side effects.
 Alberti, K. G., Eckel, R. H., Grundy, S. M., Zimmet, P. Z., Cleeman, J. I., Donato, K. A., … & Smith Jr, S. C. (2009). Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; American heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity. Circulation, 120(16), 1640-1645.
 Solomon, T. P., Malin, S. K., Karstoft, K., Knudsen, S. H., Haus, J. M., Laye, M. J., & Kirwan, J. P. (2015). Association between cardiorespiratory fitness and the determinants of glycemic control across the entire glucose tolerance continuum. Diabetes Care, 38(5), 921-929.
 Braun, B., Eze, P., Stephens, B. R., Hagobian, T. A., Sharoff, C. G., Chipkin, S. R., & Goldstein, B. (2008). Impact of metformin on peak aerobic capacity. Applied Physiology, Nutrition, and Metabolism, 33(1), 61-67.