Rybelsus vs. Metformin 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

Waffles versus pancakes, red wine versus white, The Bachelor versus Love Is Blind, Rybelsus® versus metformin — we all have our personal preferences (Team Waffles over here). But when it comes to your health and which medications to take, we’d bet you want to make as informed a choice as possible.

Whether you’re on a health journey to manage obesity, diabetes or both, you’ve probably been bombarded with ads, articles and social media posts about medication options. So how do you choose between metformin versus Rybelsus, two prescription medications for diabetes that may also help with weight loss?

Rybelsus and metformin for weight loss can each be beneficial in reaching the health goals you and your doctor come up with — but there are differences between the medications you’ll want to know about.

Whether Rybelsus or metformin is best for your needs depends on several factors, such as your health, your diabetes treatment plan, whether weight management is a factor and more.

On the surface, Rybelsus versus metformin have many similarities:

  • Both are prescribed for diabetes. Rybelsus and metformin are used to lower blood glucose levels (blood sugar) in adults with type 2 diabetes.

  • Both are offered as oral medications. Rybelsus comes as an oral tablet. Metformin oral medications are available in multiple forms, including extended-release tablets under the brand name Glumetza® and immediate-release tablets.

  • Both are prescribed off-label for weight loss. Although the FDA (U.S. Food and Drug Administration) has only approved these drugs for diabetes, both Rybelsus and metformin are sometimes prescribed as off-label weight loss medications (when an FDA-approved drug is used to treat something other than what it’s approved for).

But with all these similarities, there are key differences between metformin versus Rybelsus for weight loss, diabetes and more.

Both drugs are prescribed to manage blood sugar levels in adults with diabetes, although neither is intended for type 1 diabetes. Metformin is often recommended as a first-line treatment by the American Diabetes Association.

But one big difference between these two medications is how they work.

How Does Rybelsus Work?

Let’s start with Rybelsus. The active ingredient in Rybelsus is semaglutide — the same active ingredient in two other diabetes or weight loss medications you might have heard of, Ozempic® and Wegovy®. Think of Wegovy as the injectable weight loss medication version of Rybelsus.

Along with Ozempic and Wegovy, Rybelsus belongs to a class of medications called glucagon-like peptide-1 receptor agonists — or GLP-1 receptor antagonists for short.

These drugs mimic the hormone GLP-1, essentially boosting insulin production in your body while targeting areas of the brain that regulate appetite. This lowers blood sugar levels while helping to reduce body weight.

How Does Metformin Work?

Metformin works differently. Belonging to a drug class called biguanide, one of the ways this medication is thought to keep blood sugar in check by causing your liver to produce less glucose. 

Metformin may also reduce appetite, potentially leading to weight loss.

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Weight loss treatment that puts you first

So how effective are each of these diabetes drugs when it comes to weight management?

Fortunately, we have receipts on the effectiveness of Rybelsus versus metformin for weight loss. And by receipts, we mean scientific studies, of course.

Does Metformin Cause Weight Loss?

Metformin caused a decrease in body mass index (BMI) in over 1,000 people across 21 studies. It was especially effective in higher doses with long-term treatment, which resulted in larger reductions in BMI.

Does Rybelsus Cause Weight Loss?

Rybelsus and other semaglutide drugs (like Ozempic and Wegovy) have also known significant effects on weight loss across several clinical trials.

Is Rybelsus or Metformin Better for Weight Loss?

But — the burning question on your mind — how does metformin versus Rybelsus for weight loss stack up? Is one better than the other?

A small study comparing GLP-1 receptor agonists and metformin (like Rybelsus or Ozempic versus metformin) found that the group receiving GLP-1 meds lost more weight than the metformin group — around 10 pounds more over 12 weeks.

One thing to keep in mind about this study, however, is that the medications were only tested on 78 people, with only 64 completing the 12-week treatment. The point is, larger studies need to be done comparing metformin versus Rybelsus.

Can You Take Metformin and Rybelsus together?

A healthcare provider might prescribe both metformin and Rybelsus to be taken together to help control glucose production if one isn’t working effectively on its own. As for weight loss, that’s something you’ll need to discuss with a medical professional.

But before you go out and ask your healthcare provider for either prescription, there are a few other things to know.

Rybelsus oral tablets are available in 3, 7 and 14-milligram (mg) dosages. Metformin oral tablets come in three different strengths: 500, 850 and 1,000 milligrams.

But the active ingredients are different, so this doesn’t mean metformin is 100(ish) times as strong as Rybelsus.

In either case, your provider will likely start you on the lowest dose and may increase it over time.

Since metformin is a decades-old drug available in generic form, it’s more affordable.

Meanwhile, a Rybelsus prescription can run you upwards of $1,000 a month. It might be covered by insurance for those with diabetes, but if it’s prescribed off-label for weight loss, you’ll likely have to pay out of pocket.

Of course, every medication comes with the possibility of experiencing side effects — and metformin and Rybelsus are no different.

Side Effects of Rybelsus

The most common side effects of Rybelsus include:

  • Nausea

  • Abdominal pain

  • Diarrhea

  • Decreased appetite

  • Vomiting

  • Constipation

In some cases, people using Rybelsus can develop pancreatitis. This medication also has a black box FDA warning about an increased risk of C-cell thyroid tumors.

Side Effects of Metformin

Metformin can cause similar side effects, including:

  • Diarrhea

  • Nausea

  • Vomiting

  • Abdominal pain

  • Constipation

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

In rare cases, metformin may lead to lactic acidosis. This is when lactic acid builds up in the blood due to muscles being unable to break down glucose.

Considerations and Drug Interactions

Beyond side effects, allergic reactions can happen in rare cases. You’ll also want to check with your healthcare provider about potential drug interactions if you’re currently taking other medications or supplements.

Additionally, your provider can offer medical advice as to which medications might be safe and effective based on any other medical conditions you have, like heart disease or kidney problems.

Your weight loss journey is your own, so it makes sense to want to be as informed as possible about potential medications. But unlike which reality dating show you prefer, which medication you choose can hinge on several factors.

Here’s the takeaway:

  • Both metformin and Rybelsus are prescribed to lower blood sugar levels in people with type 2 diabetes as well as off-label for weight loss.

  • While metformin helps your body produce more insulin and controls appetite to reduce weight, Rybelsus mimics a hormone called glucagon-like peptide-1 to regulate insulin.

  • Both medications have been shown to cause moderate weight loss, although Rybelsus has slightly more of an effect on weight management.

Between seeing the hundredth ad promoting weight loss medications or a local store selling Rybelsus and metformin for weight loss, weight management can be overwhelming.

But it doesn’t have to be (leave the overwhelming feeling for when you can’t decide between waffles or pancakes). Connect with a healthcare professional to learn more about your weight loss treatment options.

11 Sources

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  6. Semenya, A. M., & Wilson, S. A. (2020). Oral Semaglutide (Rybelsus) for the Treatment of Type 2 Diabetes Mellitus. American Family Physician, 102(9), 627-628. Retrieved from https://www.aafp.org/pubs/afp/issues/2020/1115/p627.html
  7. Yerevanian, A., & Soukas, A. A. (2019). Metformin: Mechanisms in Human Obesity and Weight Loss. Current obesity reports, 8(2), 156–164. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520185/
  8. Pu, R., Shi, D., Gan, T., Ren, X., Ba, Y., Huo, Y., Bai, Y., Zheng, T., & Cheng, N. (2020). Effects of metformin in obesity treatment in different populations: a meta-analysis. Therapeutic advances in endocrinology and metabolism, 11, 2042018820926000. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243386/
  9. Gao, L., Huang, H., Zhang, L., Zhang, N., Fu, Y., Zhu, D., Bi, Y., & Feng, W. (2022). Comparison of Beinaglutide Versus Metformin for Weight Loss in Overweight and Obese Non-diabetic Patients. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 130(6), 358–367. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9286864/
  10. Metformin Prices, Coupons, Copay & Patient Assistance. (n.d.). Drugs.com. Retrieved from https://www.drugs.com/price-guide/metform
  11. Rybelsus Prices, Coupons, Copay & Patient Assistance. (n.d.). Drugs.com. Retrieved from https://www.drugs.com/price-guide/rybelsus
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