Ozempic vs. Metformin: how do they compare?

If you have type 2 diabetes or are looking to manage your weight, your healthcare provider may have recommended treatment with Ozempic, metformin (or both). Ozempic (semaglutide) and metformin are both prescription medications that may be prescribed to treat type 2 diabetes or help with weight loss. 

Ozempic and metformin also share some side effects, but their similarities stop there. Ozempic and metformin work differently. One is a weekly injectable medication, while the other is an oral tablet swallowed daily. And they vary widely in price and availability. 

Read on as we break down the differences and similarities between Ozempic vs. metformin so you can make an informed decision about your treatment options.

Here is a quick look at the main differences between metformin vs. Ozempic (semaglutide). For more details, keep reading.

1. Both treat type 2 diabetes and can promote weight loss and lower cardiovascular risk

Both Ozempic and metformin are FDA-approved to treat type 2 diabetes mellitus by controlling blood sugar levels. Both medications work best when combined with lifestyle changes like diet and exercise. Ozempic is also FDA-approved to lower the risk of stroke, heart attack, or death in adults who have both type 2 diabetes and heart disease. While metformin is not officially FDA-approved to lower cardiovascular risk, research shows that it significantly reduces the risk of death, heart attack, and stroke in people with type 2 diabetes.

Ozempic and metformin may also be prescribed off-label for weight loss. Additionally, metformin may be prescribed off-label to treat prediabetes, gestational diabetes, irregular periods due to polycystic ovary syndrome (PCOS), or weight gain caused by antipsychotic medications. Off-label prescribing allows physicians to use their expertise to prescribe the best medication for their patients, even if it is not explicitly approved by the FDA to treat a certain condition. 

The active ingredient in Ozempic, semaglutide, is also available under the brand name Wegovy in different dosages, and Wegovy is actually FDA-approved for weight management. 

2. Ozempic and metformin lower blood sugar in different ways

Metformin and Ozempic have different mechanisms of action. They both lower blood sugar and can affect weight, but they do so in different ways. 

Metformin belongs to a drug class known as biguanides. These diabetes medications work by lowering both the amount of glucose (sugar) released by the liver and the amount of glucose your intestines absorb from your food. Metformin also boosts your insulin sensitivity (which helps with diabetes). Together, these effects help to control blood sugar levels.

As a glucagon-like peptide-1 (GLP-1) receptor agonist, Ozempic works by mimicking GLP-1, a hormone your body produces naturally. GLP-1 agonists like Ozempic encourage the pancreas to release insulin while simultaneously reducing the production of glucagon (a hormone that makes you feel hungry) so your blood sugar levels stay in check. At the same time, Ozempic sends satiety (fullness) signals to your brain and slows digestion so you feel full sooner. Together, these effects keep blood sugar levels within a healthy range while also reducing your appetite and causing you to eat less — leading to weight loss. 

Because Ozempic tends to promote weight loss, healthcare providers may prescribe Ozempic off-label for this purpose, whether or not their patient also has type 2 diabetes. The same holds true for metformin, although it is not as effective at promoting weight loss as Ozempic. Metformin helps promote weight loss by reducing your appetite hormone levels and your body's absorption of carbohydrates. Metformin also boosts levels of GLP-1, further decreasing appetite and blood sugar levels. Metformin tends to produce more weight loss in people with more insulin resistance. 

3. Ozempic produces more weight loss than metformin

Both drugs may be prescribed off-label to help with weight loss, but Ozempic produces more weight loss than metformin. While Ozempic can reliably contribute to weight loss, metformin is considered “weight neutral” by the American Diabetes Association, meaning that some people may neither lose nor gain weight while taking it. 

When metformin does lead to weight loss, the results are modest. For example, a study of people with prediabetes found that while taking metformin reduced their risk of type 2 diabetes by about one-third, it only led to a weight loss of around 4–5 pounds.

Given its weight loss effects, Ozempic may be recommended to people who have both type 2 diabetes and a higher body weight. In clinical trials, people taking Ozempic have lost anywhere from 4%–5% of their body weight within seven months, with people taking a higher dosage of Ozempic losing more weight. When combined with metformin or thiazolidinedione, another diabetes medication, people taking Ozempic lost 5%–7% of their body weight after about a year. 

Studies show that the weight loss results may be even more pronounced for people without type 2 diabetes, with either Ozempic or metformin. For example, people with obesity (but not diabetes) lost nearly 13 pounds within six months on metformin. 

4. Ozempic is a once-weekly injectable medication, while metformin is a daily oral medication

Metformin and Ozempic differ in their dosage forms and strengths. 

Ozempic is an injectable medication that comes in a prescription pen. You take Ozempic once a week by injecting it subcutaneously (under the skin) of your thigh, abdomen, or upper arm. It’s best to rotate through the injection sites each week. If you take insulin, you should avoid injecting both Ozempic and insulin into the same place, taking care to inject them in different locations. You can take Ozempic any time of day, regardless of when you last ate. 

Ozempic is available in four dosage strengths: 0.25 mg, 0.5 mg, 1 mg, and 2 mg. Typically, your healthcare provider will start you at the lowest dose of 0.25 mg and then slowly increase your dosage every few weeks until you reach a dosage that best suits your health needs while minimizing side effects.

Metformin is an oral tablet that you take 1–3 times per day, depending on your healthcare provider’s instructions. It is available in both immediate-release and extended-release versions. Similar to Ozempic, healthcare providers typically prescribe a lower starting dose of metformin — either 500 mg twice a day or 850 mg once a day—to be taken at the same time you have a meal. Over a period of weeks, they will slowly titrate your dose up until they find a dosage that effectively controls your blood sugar levels (or produces weight loss). The maximum dosage of metformin is 2,550 mg for adults and 2,000 mg for children ages 10 to 16.

5. Ozempic and metformin can both cause digestive side effects

Ozempic and metformin share several of their most common side effects, including:

• Nausea

• Vomiting

• Diarrhea

• Abdominal pain or discomfort

• Constipation

• Indigestion 

• Flatulence

While less common, other Ozempic side effects may include belching or acid reflux. Additional side effects of metformin may include:

• Weakness

• Headache

• Abnormal stools

• Muscle aches

• Lightheadedness

• Shortness of breath

• Nail changes

• Rash

• Increase in sweating

• Changes in taste

• Chest discomfort

• Chills or flu-like symptoms

• Heart palpitations

• Flushing

Taking an extended-release version of metformin has been shown to reduce gastrointestinal side effects. With Ozempic, gastrointestinal side effects tend to be most common when starting treatment and increasing your dose.

Serious side effects of Ozempic may include pancreatitis, diabetic retinopathy (vision loss or changes), hypoglycemia (low blood sugar), kidney or gallbladder issues, or an allergic reaction to Ozempic. 

Metformin has a lower potential for serious side effects, although it may lead to kidney issues in older adults. Excessive drinking should be avoided while taking metformin. Studies have shown that taking higher doses of metformin can lead to a vitamin B12 deficiency, although this can be prevented by taking a daily multivitamin and ensuring your diet has enough vitamin B12. 

6. Metformin and Ozempic are recommended for different people

Another key difference between metformin vs. Ozempic is in who can take these medications. Ozempic is FDA-approved for people over the age of 18, while both adults and children ages 10 and up can take metformin. 

While both drugs are safe and well-tolerated by many people, they are not the best choice for everyone. In the case of Ozempic, this medication should not be taken by anyone with a personal or family history of certain thyroid conditions, including medullary thyroid carcinoma and multiple endocrine neoplasia syndrome type 2 (MEN 2). Ozempic should not be used while pregnant or breastfeeding and, ideally, should be stopped at least two months prior to getting pregnant. 

Additionally, people taking oral medications should be sure to give their healthcare provider a full list of medications before starting Ozempic. Because the drug slows down digestion, it may affect the absorption of oral medications.

Metformin should not be taken by people with an increased risk of:

• Kidney failure

• Lactic acidosis

• Liver problems

• Heart failure 

7. Metformin is available as a generic, while Ozempic is not yet

As a newer medication, a generic version of Ozempic is not yet available and likely won’t be for some time. Also, Ozempic is often either in shortage or about to be due to the surge in demand for injectable weight loss medications. In order to ensure priority for existing patients, Novo Nordisk has adjusted its production supply of different formulations. For example, at the time of writing, one of the starting formulations of Ozempic is discontinued as the company works on ramping up production of the other formulations. 

Metformin, on the other hand, is a commonly available generic medication. The brand names of metformin are Fortamet, Glucophage, and Riomet (regular release); and Glucophage XR and Glumetza XR (extended release). Metformin is also available in other diabetes medications that combine metformin with another active ingredient. These include:

• ActoPlus Met and ActoPlus Met XR (metformin and pioglitazone)

• Avandamet (metformin and rosiglitazone)

• Glucovance (metformin and glyburide)

• Invokamet (metformin and canagliflozin)

• Janumet and Janumet XR (metformin and sitagliptin)

• Jentadueto (metformin and linagliptin)

• Kazano (metformin and alogliptin)

• Kombiglyze XR (metformin and saxagliptin)

• Prandimet (metformin and repaglinide)

• Synjardy (metformin and empagliflozin)

• Xigduo XR (metformin and dapagliflozin)

Ozempic costs significantly more than metformin. This is partly due to the fact that Ozempic is still only available as a brand-name drug, while metformin is available as a generic. Without insurance, metformin costs anywhere from $4 to $40 for a pack of sixty 500 mg tablets (roughly a month’s supply of metformin). The price of Ozempic, on the other hand, is $935.77 for a one-month supply without insurance.

As with any prescription drug, the price you pay for Ozempic or metformin will vary depending on your insurance coverage and the pharmacy you use. Certain websites, like GoodRx, aggregate savings coupons for pharmacies across the U.S. If you have commercial or private insurance, you may qualify for the Ozempic Savings Card and pay as little as $25 for a month’s supply of Ozempic. You can also call around to different pharmacies in your area to find the cheapest price. When prescribed to treat type 2 diabetes, Medicare and Medicaid typically cover both Ozempic and metformin.

Both Ozempic and metformin can be great options for managing type 2 diabetes and body weight. The best option for you can depend on a number of factors, including your age, medical history, tolerance for side effects, insurance coverage, and budget. 

Given its wide availability, low cost, and the fact that it has simply been around for longer, metformin is often the first-line treatment for controlling blood sugar levels. However, if you also have obesity or cardiovascular disease, your healthcare provider may recommend Ozempic first since it can lead to more significant weight loss and is FDA-approved to lower cardiovascular risk as well (although metformin has also been shown to reduce the risk of death from heart disease). It is also possible that your healthcare provider may recommend taking Ozempic and metformin together, as combining the medications can further control blood sugar levels. 

Your health insurance coverage and budget can also play a role in your decision. When prescribed to treat type 2 diabetes, both metformin and Ozempic are usually covered by private insurance, Medicare, and Medicaid. If you’re taking either medication for weight loss, this is considered an off-label purpose and is typically not covered by insurance. As a brand name-only medication, Ozempic carries a much higher price tag than metformin. 

If you’re not sure whether Ozempic or metformin is right for you, talk to your healthcare provider. They can recommend a treatment plan that includes Ozempic, metformin, both, or another diabetes medication entirely.

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Current version

February 23, 2024

Written by

Amelia Willson

Fact checked by

Yael Cooperman, MD

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About the medical reviewer

Yael Cooperman, MD, Ro

Yael Cooperman is a physician and works as a Senior Manager, Medical Content & Education at Ro.