Zepbound vs. metformin: How they compare for weight loss

When comparing medications for weight loss, there’s lots to consider: Pills or injections, cost and insurance coverage, side effects and risks—and, most importantly, what’s best for your specific body and biology. 

At Found, our MetabolicPrint™ process helps take some of the guesswork out. But when you’re trying to zero in on the right treatment  for your unique weight loss needs, studying different medications side by side is an important part of the process. 

Here, we’re going to look at how the newest weight-loss drug, Zepbound®, stacks up with metformin, one of the oldest type 2 diabetes treatments (which is also prescribed off-label for weight loss). 

When comparing Zepbound vs metformin, which (if either) might be the best choice for you? Let’s explore.

Zepbound vs. metformin: How do they work?

Zepbound, made by Eli Lilly, is a prescription medication the U.S. Food and Drug Administration (FDA) approved for chronic weight management in 2023. A dual-agonist GLP-1/GIP, the drug is intended for people with obesity or for those with excess weight and at least one weight-related health condition like high blood pressure or sleep apnea. Zepbound is a once-weekly injection. 

Tirzepatide, the active ingredient in Zepbound (and Mounjaro®, a Lilly medication that is FDA-approved to treat type 2 diabetes), mimics two of the body’s naturally produced gut hormones. These hormones—glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)—help regulate blood sugar, stomach-emptying, and appetite. Zepbound helps control blood sugar and hunger so people eat less, feel fuller longer, and lose weight. 

Metformin, on the other hand, is the most commonly used oral medication for type 2 diabetes in the world. It’s derived from the medicinal herb goat’s rue, whose effects on blood glucose levels have been noted for over a century. Metformin has been used clinically since the late 1950s and was FDA-approved as a prescription treatment for type 2 diabetes mellitus in the mid-1990s. Now, it’s often prescribed off-label for weight loss. 

Metformin (also called metformin hydrochloride) is available in regular and extended-release tablets, as a generic prescription medication, and under several brand names.

Metformin helps the body regulate blood sugar levels and use insulin more efficiently, which can suppress appetite and has been shown to aid in weight loss. Some recent research suggests metformin may also encourage the production of an “anti-hunger” molecule, much like those triggered naturally by intense exercise. 

Zepbound vs metformin: How much can you lose—and how fast?

Individual results vary, of course. However, in one clinical trial, people who took a maximum tolerated dose of Zepbound (10 mg or 15 mg) each week with diet and exercise lost an average of 20.9% of their body weight after 36 weeks. The study involved people with obesity (a body mass index, or BMI, of 30 or higher) and people with excess weight (a BMI of 27 or higher) with one weight-related health condition. What’s more, those who continued taking the drug maintained that weight loss—and lost an additional 5.5% of body weight over the next 52 weeks. (Use our free BMI calculator to check your body mass index.) 

And metformin? In one study testing intensive lifestyle intervention and metformin use vs placebo, 28.5% of those in the metformin group lost 5% or more of their body weight after one year, while only 13.4% of those taking placebo achieved similar weight loss. In an observational study of 199 patients with a BMI of 27 or greater, 154 were treated with metformin daily, and 45 were untreated as a control. After six months, the average weight loss among those taking metformin was 12.8 to 15.4 pounds, while those who did not receive metformin gained an average of 1.7 to 7.7 pounds. 

On either drug, it may take several months to see noticeable changes in body weight. 

Zepbound vs metformin: How much do they cost per month? 

Without insurance coverage or discount coupons, Zepbound costs upwards of $1,086 for four pre-filled injector weekly pens of any dosage. The list  price is $1,086.37, but pharmacy prices are typically higher. Eli Lilly also makes Zepbound in single-dose vials, available from Lilly Direct. A four-week supply of the two lowest Zepbound dosages (2.5 mg and 5 mg) costs $349 or $499, respectively. There are also 7.5 mg and 10 mg doses in single-dose vials. The vials require users to draw up and inject the medication with a syringe.‍

Costs for metformin vary somewhat depending on dosage, brand name, and type of tablet (regular vs extended-release). Still, metformin can be as much as 100 times less expensive than Zepbound. Recent checks on GoodRx.com found monthly fills of 60 (500 mg) tablets of non-brand-name metformin ranging from $4 to $19 at major pharmacy chains before discounts or insurance. ‍

Zepbound vs metformin: Side effects & warnings

Some of the most commonly reported side effects for both medications are gastrointestinal issues (nausea, vomiting, stomach discomfort, diarrhea, constipation) as patients get used to taking the drug or adjust to a higher dose. 

For Zepbound (tirzepatide), other common side effects include skin reactions at the injection site and feeling tired. Muscle loss may also happen, which is one reason it’s important to strength train and exercise regularly while taking Zepbound.

More serious side effects of Zepbound include low blood sugar (hypoglycemia), severe stomach, kidney, gallbladder or pancreas problems, diabetic retinopathy, and depression or thoughts of suicide. Tell your health care provider if you have severe stomach problems that won’t go away, including abdominal bloating or pain, acid reflux, a feeling of fullness after eating just a few bites of food, nausea, and vomiting, including vomiting undigested food eaten a few hours earlier. These may be symptoms of gastroparesis, a paralysis of the stomach muscles.

Zepbound carries a “black box” warning about thyroid cancer because clinical studies link it to C-cell thyroid tumors in animals. That’s why people who have had thyroid cancer and those with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 should not take Zepbound. Nor should those who are pregnant, breastfeeding, or planning to become pregnant, as Zepbound can cause fetal harm. You can find more detailed side effect and risk information on our dedicated Zepbound page.

And metformin’s side effects? Studies show that in rare cases, long-term use of metformin may lead to pancreatitis, hepatitis, abnormal blood clotting, vitamin B12 deficiency, or reactive hypoglycemia. 

The FDA also has a “black box warning” on metformin, which notes that metformin can increase the risk of developing a serious and potentially fatal condition called lactic acidosis. This is when too much lactic acid builds up in the blood, which can cause low blood pressure, breathing issues, heart failure, and even death.

Additionally, metformin may stimulate ovulation and increase the risk of unintended pregnancy in premenopausal women and those with polycystic ovary syndrome (PCOS). If you’re in a sexual relationship that can result in pregnancy, use at least one form of birth control while on metformin unless you’re planning on getting pregnant. You can find more detailed side effect and risk information on our dedicated metformin page. 

Zepbound vs metformin: Which is better for weight loss? 

In truth, it depends. Every person and each body differs. Research into a single drug is limited in people with overlapping medical conditions and those taking multiple medications. The medication that’s more effective in a clinical trial setting may not be the one that works best—or be the safest and most sustainable—for you. 

That’s why getting your MetabolicPrint, designed by the obesity medicine specialists at Found, can be so helpful. Take the quiz to get started today.

About Found

Found is among the largest medically-supported telehealth weight care platforms in the country, having served more than 250,000 members to date. To discover your MetabolicPrint™ and start your journey with Found, take our quiz. 

Found is not affiliated with or endorsed by Eli Lilly and Co., the owner of the registered trademarks Mounjaro® and Zepbound®. The content provided is for informational purposes only and should not be used as a basis for diagnosing or treating any health condition, or for determining actual costs incurred. Always follow your health care provider’s instructions to ensure safe and effective management of your health conditions. Certain medications are only FDA-approved to treat conditions other than weight but may be prescribed to help aid in weight loss. Prescriptions are up to a medical provider’s discretion. For key risk information by drug, visit the Found medication page.