What is the difference between metformin and Ozempic?

More than 38 million adults in the U.S. are living with type 2 diabetes, according to the Centers for Disease Control and Prevention. And for many, medications like metformin and Ozempic can be key for managing the disease. But while both have the same goal — to keep blood sugar under control — they go about it pretty differently. There’s the old guard, metformin, which was FDA-approved in 1994 and remains a go-to trusted option. And then there’s one of the newer kids on the block, Ozempic (semaglutide), which is a GLP-1 approved in 2017. Here’s what you need to know so you can walk into your next appointment informed, empowered, and ready to talk options.

What is metformin?

First introduced in Europe in the 1950s and approved by the U.S. FDA in 1994, metformin has stood the test of time and become one of the most widely prescribed medications for type 2 diabetes. Prescribed under multiple brand names, it’s currently used by more than 150 million people worldwide. It belongs to a class of drugs called biguanides and is usually part of a broader treatment plan that includes healthy eating habits and regular movement.

Metformin reduces the amount of sugar your liver releases into the bloodstream — which helps keep blood sugar levels in check. A metformin prescription may come in either immediate- or extended-release forms and can be used alone or in combination with other medications like insulin or sulfonylureas.

What is Ozempic?

Ozempic is the brand name for semaglutide, an injectable prescription medication that was FDA-approved in 2017 to help manage type 2 diabetes. It belongs to a class of drugs called glucagon-like peptide-1 receptor agonists (more commonly known as GLP-1s), which mimic a natural hormone in your body. Ozempic helps regulate blood sugar by boosting insulin production when you eat, slowing down digestion, and reducing appetite. Unlike metformin, which helps the body respond better to the insulin that’s already there, “Ozempic promotes the secretion of insulin,” explains Dr. Silvana Pannain, M.D., associate professor of medicine at the University of Chicago.

An Ozempic prescription is typically considered when other medications, like metformin, aren’t sufficient on their own — particularly for individuals who may also benefit from weight loss, as Ozempic suppresses appetite and can lead to significant weight reduction. In 2025, the American Diabetes Association updated their recommendations and said that Ozempic and other GLP-1s should be considered as a first line therapy for certain high-risk patients.

More recently, Ozempic’s approved uses have expanded beyond blood sugar control. In 2020, it was FDA approved to help lower the risk of serious heart problems, such as heart attack, stroke, and cardiovascular-related death, in people with type 2 diabetes and heart disease. Then, in 2025, Ozempic was approved to help reduce the risk of kidney disease progression, kidney failure, and cardiovascular-related death in people with type 2 diabetes and chronic kidney disease, broadening its role in long-term diabetes care.

5 key differences between Ozempic and metformin

While both medications are used to help manage type 2 diabetes, that’s about where the similarities end. “They work in completely different ways,” says Pannain. Here’s how they stack up.

1. They belong to different drug classes. Metformin belongs to a class of medications called biguanides, which work by helping your body respond better to insulin and reducing how much sugar your liver releases into your bloodstream. Ozempic (semaglutide) is a GLP-1 receptor agonist, meaning it mimics a natural gut hormone to boost insulin levels, slow digestion, and reduce appetite.
   
   
2. They come in different forms. Metformin is taken as a daily oral pill, while Ozempic is a once-weekly injection that you give yourself using a prefilled pen.
   
   
3. They’re approved for different age groups. Metformin is FDA-approved for children 10 and older while Ozempic is currently approved for adults 18 and older.
   
   
4. Only one has a generic version. Metformin is the active ingredient in several type 2 diabetes medications and is available in both brand-name (like Glucophage) and generic forms, making it widely accessible and more affordable. Ozempic, still only offered as a brand-name drug, can come with higher out-of-pocket costs.
   
   
5. They affect weight differently. Metformin can lead to an average of 2.5% weight loss in six months, while Ozempic can lead to almost 11% weight loss in the same time frame.

Metformin vs. Ozempic: uses

Approved by the FDA in 1994 to treat type 2 diabetes, metformin is a long-standing first-line treatment that helps lower blood sugar by reducing glucose production in the liver.

Ozempic was FDA-approved in 2017 to help manage blood sugar in adults with type 2 diabetes. More recently, it also received FDA approval to help reduce the risk of severe heart problems, kidney disease progression, kidney failure, and cardiovascular-related death in certain populations. While it’s not officially approved for weight loss (that’s what the version of semaglutide prescribed under the name Wegovy is approved for), many people on Ozempic do lose weight as a secondary effect.

Metformin vs. Ozempic: dosages and administration

Metformin is an oral medication taken daily — often with meals to ease potential stomach upset. It comes in four strengths (500 mg, 750 mg, 850 mg, and 1,000 mg), and a typical adult starts at one of the three lower doses once or twice daily, with gradual dose increases as needed. The maximum daily metformin dose is typically 2,500 mg to 2,550 mg. For children 10 and up, the maximum is generally 2,000 mg per day.

Ozempic is a once-weekly injectable medication delivered via a prefilled pen in one of four doses: 0.25 mg, 0.5 mg, 1 mg, and 2 mg. Most people start on a low Ozempic dose to help their body adjust and reduce the risk of side effects. From there, the dosage is gradually increased under a doctor’s guidance until an effective and tolerable maintenance dose is reached.

Here’s a typical dosing schedule of someone starting out on Ozempic (assuming they’re going to go up to the maximum dose):

• Weeks 1–4: 0.25 mg weekly
• Weeks 5–8: 0.5 mg weekly
• Weeks 9–12: 1 mg weekly
• Week 13 and beyond: 2 mg weekly

Effectiveness of metformin vs. Ozempic

Metformin has been the go-to starting medication for type 2 diabetes for years — and for good reason. It’s affordable, well-studied, and can lower A1c (a key measure of blood sugar) by about 1%. But for people who need more support, Ozempic can offer an extra boost. On its own, it can lower A1c by up to 1.6%.

Research also shows that combining Ozempic with metformin can lead to even greater improvements in blood sugar control, especially for those who are overweight or managing other risk factors. One study found that combining semaglutide and metformin led to an average A1c reduction about 1.1% greater than metformin alone. Since metformin improves the action of insulin and Ozempic promotes the secretion of insulin, “they may have almost a synergistic effect,” Pannain says.

Metformin vs. Ozempic: cost and insurance coverage

When it comes to cost, metformin is one of the most affordable diabetes medications available. In 2022, the average out-of-pocket cost was just $4.34, thanks to its long-standing availability as a generic. Ozempic, on the other hand, comes with a much higher price tag. The list price for a one-month supply, regardless of dose, is around $997, though most people don’t pay that amount if they have insurance. Coverage varies widely by plan, so it’s important to check with your provider to see what’s included and what steps (like prior authorization) may be required. For those without insurance or who don’t qualify for coverage, manufacturer savings cards and patient assistance programs may help bring the cost of Ozempic down.

Metformin vs. Ozempic: side effects

Both Ozempic and metformin can cause gastrointestinal side effects like nausea or stomach upset, but they show up a little differently. Metformin’s side effects often fade with time, especially if you take it with food or use the extended-release version. Ozempic, on the other hand, may cause nausea that returns whenever you give yourself a dose.

Serious side effects are rare, but they do happen. Metformin carries a small risk of lactic acidosis, a serious buildup of acid in the blood that can happen when the body isn’t getting enough oxygen. Ozempic has been linked to inflammation of the pancreas, gallbladder problems, and kidney issues. There’s also a black box warning (the most serious prescription label by the FDA) for a potential risk of thyroid C-cell tumors. Keep in mind that this was only observed in rodent studies and there have not been any studies proving a link in humans. If anything feels off while taking either medication, don’t wait — your doctor can help adjust your treatment or ease side effects.

Metformin side effects

Like many medications, metformin can cause side effects. Most are mild and digestive in nature, and they’re more common with the immediate-release form of the drug as opposed to the extended-release option. Here are some of the most common ones to look out for:

• Diarrhea
• Nausea/vomiting
• Flatulence
• Indigestion
• Stomach ache
• Lack of energy
• Headache

“For metformin, [extended-release preparations] taken with food are better tolerated, and side effects typically disappear with continued use,” explains Dr. Malti Vij, M.D., adjunct associate professor of medicine at the University of Cincinnati College of Medicine.

While up to 75% of people taking metformin experience some side effects, they’re usually temporary. Still, if symptoms persist or interfere with your daily life, it’s important to talk to your doctor who can adjust your treatment plan.

For a full list of Metformin side effects, read the package insert.

Ozempic side effects

Like other GLP-1 weight-loss medications, Ozempic works by slowing down digestion. That’s why stomach-related side effects are fairly common, especially when you’re just getting started or increasing dosage. These Ozempic side effects may include:

• Nausea
• Vomiting
• Diarrhea
• Constipation
• Stomach pain

“That’s why we start low and increase gradually,” says Vij. “Doses are usually raised every four weeks to help your body adjust more comfortably.”

If you already have digestive issues like acid reflux or slow stomach emptying, it’s worth talking to your doctor about it since Ozempic could make those symptoms worse.

For a full list of Ozempic side effects, visit its website.

Metformin and Ozempic drug warnings

Before starting either medication, make sure it’s safe for you. Ozempic isn’t recommended for people with a personal or family history of medullary thyroid cancer or MEN 2, and it’s not advised during pregnancy or breastfeeding. If you’ve had pancreatitis, gallstones, or a severe allergic reaction to Ozempic, talk to your doctor about alternatives.

Metformin carries a rare risk of lactic acidosis, a serious buildup of acid in the blood, especially in people with kidney issues. It can also lower vitamin B12 levels over time and may increase the risk of low blood sugar if taken with insulin or similar meds. Your doctor may recommend routine bloodwork and dosage adjustments to keep things on track.

The bottom line

Both metformin and Ozempic are two popular medications for treating type 2 diabetes. Metformin, which has been around in the U.S. since the mid-1990s, is a trusted, low-cost starting point that’s helped millions improve blood sugar and insulin sensitivity. Ozempic is a newer option that increases production of insulin and slows gastric emptying. Alone, Ozempic can reduce A1c levels than metformin, but they can also be combined for a bigger impact. The best medication for you depends on your unique medical history, health goals, and preferences, so be sure to discuss the options with your doctor.