This content originally appeared on Everyday Health. Republished with permission.

By Ginger Vieira

Medically Reviewed by Elise M. Brett, MD

GLP-1 medications like semaglutide (Ozempic) and tirzepatide (Mounjaro) continue to make headlines for their impact on obesity and diabetes. If you have type 2 diabetes, you’ve probably already been prescribed metformin, a common first-line treatment for the condition. If you’re taking a GLP-1 drug for the first time, you might wonder whether or not it makes sense to continue taking metformin.

Metformin is among the oldest type 2 diabetes drugs, developed over 100 years ago.[1] Why would you need such an old-fashioned and seemingly less impactful medication like metformin if you’re taking one of the newest diabetes and weight loss drugs on the market?

“Diabetes is a complex health condition,” explains Vanessa King RDN, CDCES, a spokesperson for the Academy of Nutrition and Dietetics. “If your A1C is more than 1.5 percent above your target, a combination medication therapy is now the most common strategy per the standards of the American Diabetes Association.” That means taking more than one diabetes drug at once. Even if you are meeting your blood sugar goals with metformin, your clinician may recommend adding a GLP-1 drug for its other health benefits.

In fact, these two diabetes medications work very differently even while providing similar benefits. Experts say they work better when taken together. Here’s what you need to know.

Metformin vs. GLP-1s: How Do They Work?

Metformin is a pill that patients take once or several times per day. GLP-1 medications are generally taken once a week via injection, or less commonly with a daily tablet or daily injections.

“Metformin and GLP-1s (like Ozempic) are often prescribed together to manage blood sugar levels for people with type 2 diabetes,” explains King, “because they are different types of medicine that work in synergistic and complementary ways.”

Metformin works mostly by telling your liver to produce less sugar, says King.

“Ozempic and Mounjaro, on the other hand, work by imitating gut hormones that increase your body’s insulin production when you’re eating, slow down how quickly food moves through the digestive tract, and increase satiety and fullness when you’re eating,” adds King. “GLP-1s reduce liver glucose production, too.”

While many of the benefits do overlap, each class of drugs offers different benefits.

Benefits of Metformin

Long considered the “first line of defense” in treating type 2 diabetes, metformin works primarily by suppressing how much glucose (sugar) the liver produces. It can also reduce your appetite, reduce how much sugar is absorbed from the carbohydrates you eat, and slow down the digestion of your meal. All these effects can help with a small amount of weight loss.

“There are so many benefits of metformin. Metformin actually increases your body’s natural GLP-1 production,” explains Lori Wenz, NP, a nurse practitioner who’s been caring for people with type 2 diabetes and obesity for over 10 years at Western Colorado Weight Care in Grand Junction.

But Wenz says researchers are still learning about less-obvious benefits of metformin.

“In research, we also see positive changes in the gut microbiome in people taking metformin,” says Wenz. “We know metformin changes how you absorb macronutrients, particularly carbohydrates, but possibly fats and proteins, too.”

Recent research suggests metformin can reduce your risk of developing a variety of other health conditions, too, including dementia, cancer, and age-related macular degeneration.

“There’s still so much we don’t know about the potential benefits of metformin,” says Wenz.

King points to past research that also suggests metformin can improve LDL cholesterol levels.

“Other benefits of metformin include that it is safe,” adds King. “And it doesn’t cause weight gain, is highly effective when taken consistently, doesn’t cause hypoglycemia, and it’s relatively affordable.”

While the impact of metformin is significantly more subtle and gradual than that of GLP-1s, it is still beneficial for almost anyone with diabetes, regardless of other medications.

Benefits of GLP-1s

GLP-1 drugs are almost certainly the most effective weight loss medications ever developed. Though people with diabetes tend to lose less weight using a GLP-1, the total loss can still be impressive. On the highest approved dosages, people with diabetes lose an average of 15 pounds (lb) on Ozempic, and 27 lb on Mounjaro, according to Everyday Health’s network site Diabetes Daily.

While it’s been well established that GLP-1s can help you lose weight and improve blood glucose levels, research continues to reveal other potential and significant benefits for other parts of your health.

“GLP-1s like Ozempic have cardiovascular and kidney benefits as well,” explains King. “Research shows it can protect patients with heart disease, heart failure, or chronic kidney disease. But it can also reduce your risk of these conditions if you’re high-risk, including people with diabetes.”

In research GLP-1 medications have dramatically delayed the progression of kidney disease, and reduced the risk of death from a heart attack or stroke, two serious conditions that are often complications of type 2 diabetes.[2][3]

GLP-1s and Metformin Are Most Beneficial When Combined

“We have data from past trials that tirzepatide with metformin show greater weight reduction than tirzepatide alone,” explains Wenz on the benefits of Mounjaro. “Some people think you don’t need anything else, or that metformin isn’t as effective, but we know these medications are most effective when you take them together.”

Wenz encourages her patients to take both — if they can access and tolerate both.

“Patients definitely get an additive benefit when taking metformin and Ozempic in combination,” says King.

GLP-1 and Metformin Side Effects

Both these drug families come with side effects, some of which overlap. Metformin is known to cause gastrointestinal distress, commonly diarrhea. Nausea and vomiting occur in up to 30 percent of users.[4] And GLP-1s have quickly become known for their own gastrointestinal side effects, which affect an even higher percentage of users.

“Both medications have potential digestive side effects and this can be one concern with taking them together,” says King.

“We work on a case-by-case basis to reduce the gastrointestinal side effects,” says King. “In some cases, patients do discontinue taking either medication. Thankfully, there are so many different options for diabetes medications.”

With both drugs, the most common side effects tend to subside after days, weeks, or months, as the body becomes accustomed to the new medication or a higher dosage.

Access and Affordability

It may be ideal to take both these medications — if you can access them.

“There is so much buzz around Ozempic and Mounjaro related to weight loss, but these drugs are cost-prohibitive for many people,” says King. “Many patients appreciate the low cost of metformin and the fact that it is taken orally versus an injection.”

GLP-1 medications are expensive, difficult to get insurance coverage for, and can be difficult to find because of ongoing shortages. By contrast, metformin is very affordable and easy to get insurance coverage for, too. Some insurance companies may actually require you to take metformin before you’re eligible for a GLP-1.

The Takeaway

Metformin is not as powerful as semaglutide or tirzepatide, but it still has an important role to play in type 2 diabetes treatment. While these different drugs offer many similar benefits, they work differently in the body and can be used together for an additive effect.

Resources We Trust

Mayo Clinic: The Best Injection Sites for Mounjaro
Harvard Health: Is Metformin a Wonder Drug?
American Diabetes Association: Medications for Type 2 Diabetes
Obesity Action Coalition: Lifestyle Habits to Treat Obesity
Centers for Disease Control and Prevention: About Insulin Resistance

Editorial Sources and Fact-Checking