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Metformin is prescribed for type 2 diabetes management, but research indicates it can also help with weight loss. Scott Olson/Getty Images
  • Researchers report that the diabetes drug metformin may increase your body’s production of the same molecule produced after vigorous exercise, producing weight loss benefits.
  • This molecule is known for its “anti-hunger” effects that suppress appetite.
  • Experts say that metformin can lead to modest weight loss through many pathways, but these findings primarily emphasize the value of exercise.

The diabetes medication metformin increases the body’s production of a molecule that suppresses appetite, according to a study by Stanford University in California published today in the journal Nature Metabolism.

This same molecule is also produced during and after vigorous exercise — a fact that was discovered two years ago by researchers at Stanford and Baylor University in Texas.

Known as the “anti-hunger” molecule, researchers believe the lac-phe molecule explains the slight weight loss effects of metformin, the most prescribed diabetes medication on the planet.

“Until now, the way metformin, which is prescribed to control blood sugar levels, also brings about weight loss has been unclear,” said Jonathan Long, PhD, an associate professor of pathology at Stanford and a study author, in a press statement. “Now we know that it is acting through the same pathway as vigorous exercise to reduce hunger. Understanding how these pathways are controlled may lead to viable strategies to lower body mass and improve health in millions of people.”

After trials in mice with obesity, researchers analyzed blood plasma samples from people with type 2 diabetes before and after 12 weeks of taking metformin.

Participants started on a daily dose of 500 mg, increasing gradually to 2,000 mg.

Researchers reported that during this period, the participants’ lac-phe levels increased significantly.

The researchers also analyzed blood samples in a larger study with 79 participants with diabetes and heart disease. Lac-phe levels were significantly higher in the participants taking metformin compared to those not taking the medication.

Long and his team also found the opposite to be true: blocking lac-phe production in mice reversed appetite suppression and caused them to regain weight.

“The fact that metformin and sprint exercise affect your body weight through the same pathway is both weird and interesting,” said Long.

He added that these findings could lead to the development of new weight loss medications.

Metformin, which is sold under the brand names Fortamet and Glumetza, has been shown to cause a modest weight loss within the first few months of starting the medication.

Metformin has not been approved yet by the Food and Drug Administration for use in weight loss management.

Experts in diabetes patient care say that weight loss benefits and the overall benefits of metformin extend beyond the lac-phe molecule.

“Metformin is an amazing drug,” said Aimee Jose, CDCES, a virtual diabetes educator at Diabetes Care Nurse who was not involved in the new study. Jose has supported people with type 1 and type 2 diabetes for more than 15 years and has lived with type 1 diabetes for 42 years.

“Taken orally multiple times per day, metformin has been around forever,” Jose told Medical News Today.

Jose said she has has worked with thousands of people with type 2 diabetes throughout her career, seeing the impact of metformin firsthand.

“It’s one of the safest, most affordable, and most effective diabetes medications out there. It is still the standard of care for people newly diagnosed with type 2 diabetes. That’s never going to change,” she said.

Metformin plays a significant role in supporting a person’s blood glucose levels, weight, and overall metabolic system.

“We already know that the hardest working aspect of metformin is how it reduces the overproduction of glucose in people with type 1 and type 2 diabetes,” said Jose.

That excessive production of glucose leads to increased blood glucose levels and an increased need for insulin. Insulin then stores that excess glucose as body fat — making it more difficult to manage or lose weight.

“By reducing the amount of glucose your liver makes, metformin is helping your body work more efficiently, so you’re not chasing that excess glucose all day with extra insulin — whether you’re producing that insulin yourself or taking daily injections,” Jose said.

Other functions of metformin that support weight loss effects include:

  • Reducing how much glucose is absorbed from digested food
  • Delaying how quickly digested food empties into the bloodstream
  • Increasing how quickly a person feels full while eating
  • Reducing overall appetite
  • Increasing overall insulin sensitivity

All of the above, explained Jose, can lead to modest weight loss by reducing calorie intake and insulin needs.

“All providers are aware that metformin will lead to a small amount of weight loss, but metformin isn’t a weight loss drug. It’s just a positive side effect,” added Jose. “That being said, the standard weight loss recommendation for anyone living with diabetes or obesity is 7 to 10 percent of your body weight, which means metformin can certainly help you get there when it’s combined with supportive lifestyle habits.”

“Just like Ozempic and other GLP-1 medications making headlines, you have to commit to making real changes in how you eat and exercise every single day,” emphasized Jose. “If you don’t make those changes, your weight will go right back to where it started if you stop taking these medications.”

The real message in this recent study, said Jose, is what it proves about the importance of exercise.

“The fact that this medication increases production of the same molecule that suppresses your appetite after exercise only emphasizes how important physical activity truly is,” said Jose.

“It’s not just about burning calories, exercise improves how every part of your body functions,” she added. “It is so under-appreciated and so critical. Your mental health, your entire cardiovascular system, your metabolism, your energy, your quality of sleep… daily exercise truly reaches every part of your health.”

However, Jose said, there is no silver bullet.

“Weight loss and diabetes management require a multi-pronged approach that needs to be addressed from all angles. Medications are just one part. You must utilize physical activity and sustainable, realistic nutrition habits, too,” she said.

“Many people are reluctant to even start metformin because it doesn’t make headlines like Ozempic,” said Jose. “Or they’re determined to manage type 2 diabetes without medication because of the societal stigma that taking medication means you’ve failed on your own. But if your entire metabolic system is struggling, metformin helps your body function more efficiently.”

While the effects of GLP-1 medications are nearly immediate and more dramatic than metformin, Jose urged people to appreciate the drug’s benefits.

“Most people newly diagnosed with type 2 diabetes are not checking their blood glucose levels regularly,” said Jose. “If you’re not seeing those numbers, you won’t see the gradual effects of metformin.”

It is common for people to stop taking metformin due to the drug’s potential digestive side effects.

“Metformin changes how you digest food, which means it can lead to gas, bloating, diarrhea, nausea, and more frequent bowel movements,” explained Leslie Sexton, PharmD, RPh, a pharmacist from Essex Junction, Vermont, who was not involved in the new study.

While some people don’t experience any significant digestive side effects, Sexton says, these will usually settle down after the first few weeks of taking the medication.

Sexton says the type of metformin you take also matters.

“While immediate-release metformin may be appropriate for some patients, the extended-release version can significantly decrease digestive side effects and reduce the number of daily pills to swallow. This makes it easier for patients to continue taking it as prescribed,” Sexton told Medical News Today.

Sexton estimates that 30% of the metformin prescriptions her pharmacy fills are for the older immediate-release form of the medication.

“I can’t think of any reason why a patient would need the immediate-release version over extended-release,” she said. “This is an opportunity to open up a discussion with your doctor who may simply be in a routine of prescribing and refilling immediate-release metformin.”

Sexton encourages anyone considering or already taking metformin to ask for the extended-release version to lessen those uncomfortable side effects.

“The workload on doctors, and frankly all healthcare providers, has increased tremendously in the last few years. They have less and less time to spend with each patient,” stressed Sexton. “Advocate for yourself. Speak up and ask for what you need.”

Like Jose, Sexton added the importance of making thoughtful changes in your lifestyle habits to benefit from medications like metformin.

“There isn’t a single medication that can do it all for you,” said Sexton. “You have to look at your nutrition. You have to get moving every single day. It isn’t easy, but living with type 2 diabetes means your whole metabolic system needs more support. Two ways you can help it beyond medications? Eat more whole foods and get more exercise.”