Metformin vs Semaglutide For Weight Loss

Craig Primack, MD, FACP, FAAP, FOMA

Reviewed by Craig Primack, MD, FACP, FAAP, FOMA

Written by Rachel Sacks

Published 04/07/2024

The healthcare market is currently flooded with weight loss medications, many of which were initially used to treat diabetes. Are diabetes drugs actually safe and effective for weight loss? And if so, which is best? If you’re curious about metformin versus semaglutide, you’re in the right place.

There’s lots of misinformation about weight loss medications on social media and across the internet. We’re here to separate fact from fiction on semaglutide versus metformin and help you determine if either is a good fit for you.

Before we break down the details of metformin and semaglutide, here are some key takeaways:

  • They’re FDA-approved for diabetes. Semaglutide and metformin are medications approved by the FDA (U.S. Food and Drug Administration) for the treatment of type 2 diabetes.

  • They have different active ingredients. Semaglutide is the active ingredient in brand-name medications like Ozempic®, Wegovy® and Rybelsus® (all from the pharmaceutical manufacturer Novo Nordisk). When sold as Wegovy, semaglutide is FDA approved for weight management. Metformin is available in generic form as well as a few brand names, including Glumetza®.

  • They lower blood sugar. Each medication works differently to lower blood glucose levels (blood sugar).

  • They can be prescribed for weight loss. Both can be prescribed off-label for weight loss.

  • Semaglutide might be more effective for weight loss. While metformin can lead to weight loss, it’s more likely to occur with semaglutide.

  • They can cause side effects. Whether taken for blood sugar control or weight loss, both medications can cause side effects ranging from mild to more serious.

You and your healthcare provider can come up with a treatment plan based on your health history, weight loss goals and preferences.

Metformin and semaglutide might be all over your feed, but there’s a lot more to know about each — especially when trying to make the best decision for your health journey.

Both metformin and semaglutide are FDA-approved to treat type 2 diabetes mellitus — but their uses don’t stop there.

Metformin is often prescribed off-label for managing gestational diabetes, preventing polycystic ovary syndrome (PCOS) and of course, weight loss. Off-label use means a provider prescribes it for something it’s not FDA-approved for.

Semaglutide treats different conditions, depending on the brand. Ozempic, for example, is approved for diabetes, while Wegovy is for weight management.

Ozempic is also approved to reduce the risk of major cardiovascular events, such as heart attack, heart failure, stroke and death, in adults with type 2 diabetes and heart disease.

If you have diabetes, the main goal with these medications is to lower blood sugar levels. 

Although both semaglutide and metformin are approved to help lower blood sugar levels in people with type 2 diabetes, there are some key differences when it comes to weight loss.

Keep reading for a rundown of how they work, their side effects and how each drug is taken.

How Metformin vs. Semaglutide Work

Semaglutide belongs to a drug class called GLP-1 receptor agonists — GLP-1 is short for glucagon-like peptide-1, a gut hormone. As a receptor agonist, the medication mimics this hormone in the body.

How does semaglutide help you lose weight? After you eat, semaglutide stimulates your pancreas to release insulin and slows down how fast food leaves your stomach (one of the  actions of GLP-1). This can make you feel full longer, potentially helping you eat smaller portions or go longer between meals.

Metformin is a biguanide medication. This type of drug helps your body use insulin more effectively while decreasing the amount of glucose your body makes. At high doses, it may also stimulate GLP-1.

How does metformin help you lose weight? Recent evidence suggests that the medication may help regulate your appetite, allowing for modest weight loss.

Semaglutide vs. Metformin Dosages

Not only are there different dosages of semaglutide and metformin, but semaglutide comes in different forms.

Wegovy and Ozempic are injectable weight loss medications. Dosages usually start at 0.25 milligrams (mg) each week and double every four weeks until the maximum dose of 2 or 2.4 milligrams is reached.

But Rybelsus comes as an oral tablet for diabetes treatment, available in 3, 7 and 14-milligram dosages. 

Metformin is an oral diabetes medication available in three different strengths: 500, 850 and 1,000 milligrams.

The starting dose of metformin for weight loss is usually 500 milligrams, and for diabetes, it’s 850 milligrams. Your dosage might be slowly increased over time, depending on how you react to the medication.

Side Effects of Metformin and Semaglutide

Like any medication, semaglutide and metformin each come with the possibility of side effects.

Side effects of metformin can include diarrhea, nausea, vomiting and abdominal pain. The most common side effects of semaglutide are similar, such as nausea, heartburn, constipation and diarrhea.

Less common, but still usually minor, side effects of metformin include chest discomfort, headaches, sweating, hypoglycemia (low blood sugar) and weakness.

More severe side effects can occur, with some people using Ozempic developing pancreatitis. A less frequent yet serious side effect of metformin is lactic acidosis, where lactic acid builds up in the blood because the muscles can’t break down glucose.

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Which is better, semaglutide or metformin? The answer to this is the same as the answer to which show will help you unwind after a long day, Love Island or Real Housewives — both are effective.

Metformin is considered the “gold standard” of diabetes treatment by the American Diabetes Association. Whether taking extended-release or immediate-release metformin, adults with type 2 diabetes showed lower hemoglobin A1C — blood sugar levels — over three months.

Is Semaglutide or Metformin Better for Weight Loss?

But does metformin help you lose weight? It can.

Several clinical trials found that metformin caused a modest decrease in body mass index (BMI) in those with simple obesity (when someone regularly eats more than they burn off, resulting in weight gain).

Metformin was even effective for weight loss in a small group of people without diabetes who were, insulin-sensitive and insulin-resistant.

Semaglutide is also effective at reducing body weight. A weekly dose of semaglutide resulted in an average of four to six percent weight loss in individuals with diabetes and even more weight loss in those without diabetes.

But when comparing metformin versus semaglutide for weight loss, the latter might be better. It’s shown significant weight reduction in clinical trials.

If you have diabetes and also need help with weight management, Ozempic can treat both at once. But if you’re only looking to lose weight, your provider might suggest Wegovy.

Want to know how Ozempic compares to metformin? Our blog breaks it down.

Semaglutide is often a subcutaneous injection, meaning the needle goes into your skin tissue rather than all the way into a muscle (like when you get a flu shot in your arm). You can insert the needle into your belly, thigh or the inner side of your upper arm.

The injections are taken once a week. As with Rybelsus, semaglutide can also come in oral form to be taken as a once-daily tablet.

Metformin is an oral medication taken in extended-release tablets. You take one tablet daily, with or without food.

Oral weight loss medication may appeal to people who don’t like needles (let alone injecting them into their own bodies). But others might view once-a-week injections as the easier option because you don’t have to remember to take a pill every day.

Still getting metformin and semaglutide mixed up? Totally understandable. Find answers to frequently asked questions about these weight loss drugs below.

Is Metformin the Same as Ozempic?

No. While both may be prescribed for diabetes treatment or off-label for weight loss, each is a different type of medication. Ozempic contains the active ingredient semaglutide and uses a different mechanism than metformin to lower blood sugar.

Is Semaglutide the Same as Ozempic?

Yes and no. Both contain the same active ingredient (semaglutide), but Ozempic is the brand-name version, and there’s currently no FDA-approved generic version. Also, Ozempic is specifically an injectable, whereas semaglutide is available in oral tablets too (like Rybelsus).

Can You Take Metformin and Semaglutide Together?

Semaglutide can be taken alone or with other diabetes medications, such as metformin. For instance, your healthcare provider may recommend a combination of Ozempic and metformin if your blood sugar levels aren’t controlled with just one medication on its own. But for weight loss, they’d most likely only prescribe one at a time.

Which Costs More, Metformin or Semaglutide?

The cost of metformin versus the cost of semaglutide can vary based on a couple of factors — mainly, which weight loss drugs are covered by insurance.

Since metformin has been around for decades, many lower-cost generic versions are available.

Meanwhile, brand-name versions of semaglutide like Ozempic and Wegovy  typically aren’t covered by insurance, which can make them quite costly.

The average cost of semaglutide without insurance (specifically, Ozempic) can average around $900 per month — and even approach $1,000.

So, considering cost, metformin has a clear advantage. But you should still check with your insurance provider about what medications are covered.

Before asking your healthcare provider about Ozempic for weight loss, you might consider looking into alternatives. There are other off-label medications for weight loss beyond semaglutide and metformin. 

For instance, a combination of naltrexone (used to treat alcohol dependence) and the antidepressant bupropion (called Contrave®) can be used to curb your appetite or make you feel fuller sooner.

Then there’s liraglutide. Like Ozempic and Wegovy, this injectable weight loss medication works similarly to semaglutide to suppress appetite.

The short answer: It depends.

When figuring out which medication is better, you’ll want to factor in your medical history, health goals, insurance coverage and budget.

Here’s what to keep in mind about metformin and semaglutide:

  • While both semaglutide and metformin treat type 2 diabetes, there are differences in how they work, side effects, dosages and how each drug is taken.

  • Semaglutide, a GLP-1 receptor agonist, is prescribed under the brand names Ozempic, Rybelsus and Wegovy. Metformin comes as an oral tablet medication called a biguanide.

  • Metformin has the potential to cause modest weight loss while treating diabetes. Semaglutide, on the other hand, manages blood sugar levels while resulting in significant weight loss for many who take it.

If you’re trying to determine whether metformin or semaglutide is right for you, consult a healthcare professional. They can assess your health goals and let you know if there are any drug interactions to be aware of if you’re taking other medications.

Fortunately, there are plenty of ways to find a weight loss treatment that works best for you. Explore treatment options at Hers to get started.

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