- About one in every nine adults worldwide has diabetes, and 90% of those cases are type 2 diabetes.
- People can manage type 2 diabetes through healthy lifestyle choices, such as being physically active, and medications.
- Metformin is considered the first-line treatment for type 2 diabetes.
- A new study says metformin might weaken the important improvements to blood vessel function and blood sugar control that normally comes with regular exercise.
According to the International Diabetes Federation, about one in every nine adults globally has diabetes, and 90% of those cases are type 2 diabetes.
There is currently no cure for type 2 diabetes. However, people can manage the condition through
One such medication is metformin, which has long been considered to be a
While both metformin and exercise offer health benefits for those with type 2 diabetes, such as increased insulin sensitivity, Steven Malin, PhD, professor in the Department of Kinesiology and Health in the School of Arts and Sciences at Rutgers, The State University of New Jersey, said it is not clear that these therapeutic approaches work well together.
“Metformin is the most widely used glucose-lowering medication used around the world,” Malin explained to Medical News Today. “Understanding the effects of it with exercise are important since medical doctors advise people to take metformin and exercise.”
Malin is the lead author of a new study published in The Journal of Clinical Endocrinology & Metabolism, which found evidence suggesting that metformin might weaken the important improvements to blood vessel function and blood sugar control that normally comes with regular exercise.
For this study, researchers recruited 72 adults at a high risk for metabolic syndrome — a group of conditions, including excess abdominal visceral fat, high blood pressure, and high blood sugar levels, known to increase a person’s risk for a number of diseases including type 2 diabetes.
Study participants were divided into four different groups. Two of the groups participated in high-intensity exercise while taking metformin or a placebo, while the other two groups participated in low-intensity exercise while taking metformin or a placebo, and were tracked for 16 weeks.
“About 25 years ago now, the
“The difference in prevention effects prompted thoughts that maybe adding them together would produce better effects. The thinking was [that] the difference in effectiveness could be based on mechanisms of action and if combined we could get better results,” he added.
“Previously we showed this was not the case when considering how effective insulin was at clearing sugar into cells for energy metabolism. From that work, we also noted blood pressure [did] not improve as much when people took metformin and exercise. Thus we wondered, could a low-intensity exercise program work differently with metformin than the high-intensity program we had originally provided?”
“Also, we wondered with the insulin effects and blood pressure effects, could insulin act on blood vessels differently when metformin got combined with low or high intensity exercise,” Malin told us. “Our thinking was that blood vessel function is critical for the delivery of oxygen, hormones, and nutrients to tissues like muscle for energy metabolism.”
At the study’s conclusion, the researchers found that, while exercise alone improved vascular insulin sensitivity, when metformin was added these improvements diminished.
“Improved blood vessel function is key for delivering nutrients to tissues, like sugar or glucose,” Malin explained. “If the sugar cannot be delivered to the tissue this might explain why muscles cannot use the sugar for energy as well in response to insulin. Daily, when we eat meals, insulin is typically increased to do that very job — clear glucose into tissues for energy metabolism or storage for later energy use.”
“If there are problems with sugar delivery, this could impact how the body handles blood sugar,” he continued. “Poor vessel Health is related to high blood sugars and progression to type 2 diabetes. Lastly, poor vessel function is related to hypertension. This is problematic and can promote heart disease and other vascular disease issues.”
Additionally, the scientists discovered that study participants taking metformin also experienced lower gains in aerobic fitness and reduced positive effects on inflammation and fasting glucose after exercising.
“People who [are] overweight/obese often have increased inflammation,” Malin said. “This inflammation is tied to poor blood vessel function and reduced ability of insulin to clear sugar into bodily cells.“
“Ideally, we do not want inflammation to be constantly elevated as it is seen usually in people with excess weight. Here, the preservation of inflammation suggests this factor may help contribute to poor vascular insulin sensitivity and issues with blood glucose control,” he explained.
“The blunted fitness is clinically relevant, too,” the researcher continued. “Low fitness is associated with frailty and decreased quality of life. Over time, low fitness is also associated with increased risk for all cause mortality and cardiovascular disease. Here, we see that metformin constrains the rise in fitness in people and this is consistent with prior studies.”
“We have seen, too, in past work that people who exercise with metformin indicate working out feels harder,” Malin added. “We currently are looking to analyze similar outcomes of people from this trial.”
MNT had the opportunity to speak with David Cutler, MD, a board-certified family medicine physician at Providence Saint John’s Health Center in Santa Monica, CA, about this study.
Cutler, who was not involved in the research, commented that a study casting a negative light on a medication that is generally considered safe, effective, and cheap needs to be looked at with careful scrutiny.
The study “suggests that metformin may limit some [of] the metabolic and fitness benefits of exercise,“ which “may seem discouraging but needs to be placed in context,“ Cutler told us.
“The small decline in vascular insulin sensitivity needs to be weighed against the great benefit from lowered blood sugar levels achieved with metformin,“ he emphasized. “The lowering of blood sugar results in lower risks of all diabetic complications like heart attack, stroke, kidney failure, blindness, and amputation.“
“It is unclear what if any clinical consequences there are from lower vascular insulin sensitivity, although the study suggests slightly lower exercise capacity,” he added.
“This result should not be impactful to diabetics who rely on metformin, but it may be significant to people who have explored the use of metformin for other reasons,” Cutler continued.
“Without FDA approval or general scientific consensus, metformin has been touted for supposed benefits in cancer prevention, anti-aging [and] longevity [potential], and preventing cognitive decline. These unproven benefits may not justify use of the drug if there is risk of decreased exercise capacity,” he said.
“Further studies will need to be done on non-diabetics to explore the relative benefits and risks of metformin,” Cutler added. “But for now, metformin should remain the first line medication for treating type 2 diabetes.”
