Exercise Plus Metformin in the Fight Against Diabetes

If you were to ask people with type 2 diabetes about the benefits of exercise, most would likely say that exercise lowers their blood glucose. If you were to ask them which is the medication of choice for type 2 diabetes, many would say metformin. Indeed, this is reflected in the most recent American Diabetes Association (ADA, 2015) Standards of Clinical Care: “Most patients should begin with lifestyle changes (lifestyle counseling, weight-loss education, exercise, etc.). When lifestyle efforts alone have not achieved or maintained glycemic goals, metformin monotherapy should be added at, or soon after, diagnosis, unless there are contraindications or intolerance. Metformin has a long-standing evidence base for efficacy and safety, is inexpensive, and may reduce risk of cardiovascular events…”(1) Based on these standards (and many others), one could expect that millions of people with diabetes are advised to be physically active while taking metformin. Millions more could be impacted by the potential of coprescribing physical activity and metformin considering that metformin often is prescribed to people with prediabetes, polycystic ovary syndrome, nonalcoholic fatty liver disease, children with obesity, and perhaps some cancers in the near future (e.g., there currently are more than 200 clinical trials registered on clinicaltrials.gov on metformin in cancer). Given how frequently exercise and metformin are coprescribed, it is surprising how little we know regarding potential interactions between these therapies. In this issue of Exercise and Sport Sciences Reviews, Malin and Braun (3) provide a state-of-the-art summary of the emerging research in this area. Many readers may be surprised to learn that several studies have suggested that, compared with either intervention alone, the combination of metformin and exercise often is no better, and sometimes even worse, at improving glycemic control or insulin sensitivity. Research in this area is in its infancy, and interpretation of the literature is challenging because of limitations such as small sample sizes and the rarity of longer-term clinical trials. We also have much to learn about the precise mechanisms by which these treatments can interfere with each other and in which circumstances. Nonetheless, this line of investigation has raised important questions, and the article helps to summarize the current state of knowledge on 1) combining metformin with single bouts of exercise or a few months of exercise training; 2) outcomes such as insulin sensitivity, other cardiovascular disease risk factors; and 3) other outcomes such as fitness, fuel oxidation, and exercise metabolism. The discussion also broadened to include potential interactions between exercise statins or antioxidants, which also are commonly used in our societies. Exercise specialists often are taught to characterize exercise in terms of quantity and quality (2). This article is a good reminder that exercise is not prescribed in isolation and that the context of its prescription may have as much to do with the success than the exercise prescription itself. When thinking of the implications of these findings, the obvious initial questions that people treated with metformin may have are “Should I avoid exercise if I'm taking metformin?” or “Should I avoid metformin if I exercise?” At this time, I would argue that evidence does not clearly support such avoidances. However, it is important to realize how frustrating it may feel for someone with diabetes who observes even slightly more elevated glucose concentrations on the days on which they exercise. Exercise specialists can now reassure participants that such interference between the effects of exercise and metformin has been documented by others. The increased awareness of this occurrence should help fuel the search for strategies to more optimally combine exercise and metformin to maximize glucose lowering and other benefits of these therapeutic cornerstones. Normand G. Boulé Physical Activity and Diabetes Laboratory Faculty of Physical Education & Recreation and Alberta Diabetes Institute University of Alberta Edmonton, Alberta Canada

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