Written by Kyle Ustach | BScEcon
Fact checked by Andrew Lenau, ISSA CPT & Sports Nutritionist
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Have you felt like losing weight is a never-ending battle that you can't win? If the answer is yes, or if you simply struggle with your weight, you may be considering using a weight-loss medication or fat-loss supplement.
Two of the most popular and effective weight loss medications are diabetes drugs semaglutide and metformin. While metformin and semaglutide work by lowering blood sugar, some differences separate them.
In this article, we will dive into the research to compare semaglutide and metformin to help you determine the best weight loss drug for your goals.
Table of Contents:
- What Is Semaglutide?
- What Is Metformin?
- Comparing Semaglutide and Metformin For Weight Loss & Diabetes
- Side Effects
- Cost Differences
- FAQs
What Is Semaglutide?
Semaglutide is a compound referred to as a glucagon-like peptide-1 (GLP-1) receptor agonist, which helps improve blood sugar levels by lowering blood glucose. Semaglutide mimics the GLP-1 hormone in response to eating, which causes an increase in insulin production, therefore leading to better blood sugar control.
In higher doses, semaglutide can reduce appetite and increase satiety, helping you feel full longer. Semaglutide is primarily prescribed for the treatment of type 2 diabetes mellitus and to prevent major cardiovascular events in diabetes patients; however, it is also used for chronic weight management in obese or overweight patients.
Novo Nordisk, a Danish-based pharmaceutical company specializing in diabetes medication, makes all three semaglutide medications. The three FDA-approved brands include Ozempic, Rybelsus, and Wegovy. Ozempic and Wegovy are both once-weekly subcutaneous injections, so their dosing schedule is similar.
Rybelsus is the only oral GLP-1 receptor agonist available. Wegovy is the only medication FDA-approved for weight loss, but Ozempic and Rybelsus are commonly prescribed off-label for weight management.
To learn more about the different types of semaglutide medications, check out our articles comparing Ozempic vs. Wegovy and Ozempic vs. Rybelsus.
What Is Metformin?
Like semaglutide, metformin is a medication primarily prescribed for the treatment of type 2 diabetes mellitus. While semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist, metformin belongs to the drug class called biguanides. Biguanides are oral diabetes medications that lower blood glucose levels.
The active compound in metformin is metformin hydrochloride, which is available by prescription in various forms under the brand names Axpinet, Diagemet, Glumetza, Glucient, Glucophage, Fortamet, Riomet, and Metabet. The drug is available as tablets, a liquid to swallow, and dissolvable powder.
Metformin is primarily used for lowering blood glucose levels in patients with type 2 diabetes mellitus, gestational diabetes, patients with prediabetes, and sometimes in women with polycystic ovary syndrome (PCOS) who have insulin resistance. Like semaglutide, metformin is also prescribed off-label to assist with weight loss and help those with weight-related issues, like high cholesterol and high blood pressure.
Comparing Semaglutide and Metformin
While semaglutide and metformin are both prescription drugs that affect blood sugar levels to treat diabetes or obesity, there are key differences between the two medications. In this section, we will compare the two prescriptions, examining their impacts on weight loss and blood sugar control.
Metformin vs Semaglutide: How They Work
The mechanism of action for semaglutide is activating GLP-1 receptors in response to the body eating. First, GLP-1 receptors in the pancreas increase insulin secretion, causing blood sugar levels to decrease. GLP-1 also lowers blood sugar levels by reducing the release of glucagon, a compound that prevents glucose from entering the blood.
Semaglutide also slows gastric emptying, which helps prevent spikes in blood sugar levels and slows the rate at which nutrients are absorbed. This helps improve satiety and reduce hunger by keeping you full for hours. In higher doses, semaglutide also triggers the brain to reduce appetite1.
Metformin is quite different in that it primarily targets the muscles and liver. Metformin does not directly stimulate insulin secretion but helps the body use insulin more efficiently. Metformin affects blood sugar levels by decreasing glucose production in the liver (gluconeogenesis) and improving insulin sensitivity in muscle cells.
Improving insulin sensitivity in the muscle cells allows them to use more glucose from the bloodstream and can help prevent fat storage. Metformin also decreases the amount of blood sugar that the liver produces and that the stomach or intestines absorb. In other words, it reduces the absorption of fats in the intestines, which can prevent weight gain or promote fat loss. Like semaglutide, metformin also reduces appetite to promote weight loss.
Another important action of metformin is that it activates the enzyme AMP-activated protein kinase (AMPK). AMPK stimulates insulin production and glucose transport in muscles and regulates cellular and organ metabolism2. Since metformin increases the effects of insulin without actually increasing insulin secretion, it is referred to as an “insulin sensitizer.” The primary difference in the mechanism of action is that semaglutide directly stimulates insulin secretion, whereas metformin does it indirectly.
Learn more about semaglutide in our article: How Long Does It Take Semaglutide To Work?
Which Helps Best With Diabetes?
The most common way that studies measure the effectiveness of diabetes is by measuring hemoglobin A1c (HbAc1), or the amount of blood sugar attached to hemoglobin.
One study compared metformin to a lifestyle-change fitness program for diabetes. After roughly 2.8 years, participants who received 850 mg of metformin twice daily reduced the incidence of diabetes by only 31% compared to a reduction of 58% with physical activity3. This shows that simply living a healthier lifestyle is significantly better for preventing diabetes than metformin. Despite this, metformin is effective at treating diabetes because it helps the body use its existing insulin more efficiently.
In contrast, studies have shown that semaglutide effectively improves blood glucose levels in patients with type 2 diabetes. A review of clinical trials showed that semaglutide resulted in lower hemoglobin A1c and weight reductions than the placebo and other diabetes treatments. They concluded that semaglutide is efficient for treating diabetes and weight management4.
Metformin can work to lower hemoglobin A1c (HbAc1) safely and efficiently at a low price, which makes it the first option for several doctors and patients. Semaglutide medications like Ozempic are very expensive due to a current shortage of the medicine, so metformin is often more feasible.
Metformin vs Semaglutide: Weight Loss
When it comes to comparing the two for weight loss, semaglutide has been proven highly effective for reducing body weight and helping users lose weight. One study had 175 overweight or obese patients take weekly semaglutide injections of 1.7 or 2.4 mg for six months. After three months, patients had an average drop in body weight of 5.9% and lost an average of 14.7 lbs (6.7 kg). After six months, users lost 10.9% of total body weight and an average of 27.1 lbs (12.3 kg)5.
To compare metformin for weight loss, one study measured weight loss after six months of metformin up to a dose of 2,500 mg daily. The average weight loss in the metformin group was roughly 12.8 lbs (5.8 kg). (6) So, after six months, users on semaglutide lost an average of 27.1 lbs (12.3 kg) compared to only 12.8 lbs (5.8 kg) with metformin.
Semaglutide users experienced significant weight loss in only three months (14.7 lbs) compared to what metformin users lost in six months.
If after hearing about the weight loss success you can have with semaglutide, you're ready to begin taking it, there are even ultra-convenient ways to go through the process online. Check out Fountain GLP, which prescribes custom-made semaglutide for around $80 per week and enables you to consult with a doctor without leaving home!
For more information on weight loss with semaglutide, check out our articles: How Much Weight Can You Lose On Semaglutide? and 7 Reasons You're Not Losing Weight On Semaglutide.
Dosing & Administration
One of the main differences between metformin and semaglutide is the administration. Metformin is strictly an oral medication, available in tablet form to be taken once or twice daily. Metformin is available in extended-release tablets (ER) and immediate-release (IR).
The typical starting dose for metformin medications is 500 mg once daily, taken with your last meal. Dosing is typically adjusted to 500 mg twice daily or 850 mg once daily, depending on your blood sugar levels. Doctors will almost never prescribe more than 2,000 mg a day to avoid unwanted effects.
Since there are several different brands of metformin, we will compare the typical dose to the three brands of semaglutide. Semaglutide has been proven safe for 68 weeks or longer, so you can stay on the medication long-term as long as the side effects are manageable and it is approved by a healthcare provider.
Metformin has also been proven safe for long-term use, although you should stop both medications when you achieve your weight loss goal.
Metformin versus Ozempic
Ozempic, a form of semaglutide, is a once-weekly subcutaneous injection, typically injected in the upper arm, thigh, and stomach on a rotating schedule. Ozempic users start at 0.25 mg for the first month to slowly introduce the compound and gauge side effects before increasing to 0.50 mg for the maintenance phase.
Users can increase to 1 mg or the maximum of 2 mg per week if necessary. The injection can be done any time, as long as it’s the same day of the week. The Ozempic starter dose of 0.25 is comparable to the starting dose of 500 mg once daily for metformin. Users can increase dosage as needed as long as the side effects are manageable.
Rybelsus vs Metformin
Rybelsus is the most similar type of semaglutide to metformin because it is a daily oral tablet. Rybelsus users start at 3 mg for the first month, then increase to 7 mg as needed, with a max dose of 14 mg.
Rybelsus has strict dosing protocols, requiring the dose to be taken first thing in the morning at the same time every day, 30-60 minutes before eating, with water. Metformin is usually taken twice daily, with your breakfast and final meal. The dosing protocol is not as strict with metformin, but users taking it once daily should take it at night with their final meal.
Metformin vs Wegovy
Wegovy is similar to Ozempic in dosing protocol because they are nearly identical. Wegovy is also a once-weekly injection, where users start at 0.25 mg for the first month before increasing to 0.5 mg. Wegovy also has 1.0 mg, 1.7 mg, and a maximum of 2.4 mg.
Wegovy has slightly higher doses than Ozempic because it is explicitly designed to promote weight loss. In higher doses like Wegovy, semaglutide can act as a powerful appetite suppressant.
Dosing Summary
Here's a snapshot view of the different dosing protocols for each prescription.
|
Meds |
To Start |
Maintain |
Max |
|
Metformin |
500mg |
500mg |
2,000mg |
|
Ozempic |
0.25mg |
0.5mg |
2mg |
|
Rybelsus |
3mg daily |
7mg daily |
14mg |
|
Wegovy |
0.25mg |
0.5mg |
2.4mg |
Semaglutide vs. Metformin: Side Effects
Since both medications affect the digestive system, they have similar side effects and primarily cause gastrointestinal issues. If any issues occur, please contact your healthcare provider immediately.
|
Side Effect |
Semaglutide |
Metformin |
|
Common Side Effects |
|
|
|
Nausea |
✔️ |
✔️ |
|
Vomiting |
✔️ |
✔️ |
|
Abdominal pain |
✔️ |
✔️ |
|
Constipation |
✔️ |
✔️ |
|
Diarrhea |
✔️ |
✔️ |
|
Hypoglycemia (rare) |
✔️ |
✔️ |
|
Loss of appetite |
✔️ |
✔️ |
|
Headache |
✔️ |
✔️ |
|
Rare Side Effects |
|
|
|
Metallic taste in mouth |
|
✔️ |
|
Lactic acidosis |
|
✔️ |
|
Vitamin B12 and B6 deficiency |
|
✔️ |
|
Liver and kidney disease |
|
✔️ |
|
Heart failure |
|
✔️ |
|
Injection site reactions |
✔️ |
|
|
Bleeding |
✔️ |
|
|
Burning feeling in the chest |
✔️ |
|
|
Pancreatitis |
✔️ |
|
|
Gall-bladder disease |
✔️ |
|
|
Loss/change of taste |
✔️ |
|
Metformin is prescribed to children ten or older with diabetes, whereas semaglutide is only approved in adults. Other people who should avoid taking metformin or semaglutide include those with the following:
- Thyroid issues or thyroid tumors
- Gastrointestinal disorders
- History of pancreatitis
- Kidney or liver issues
- Cardiovascular disease or issues
- Women who are pregnant, breastfeeding, or planning on becoming pregnant
- Medical history of diabetic ketoacidosis
- Family history of medullary thyroid carcinoma
In addition, you should not drink alcohol while taking the medication, as drinking alcohol can affect blood sugar levels, increasing your risk of hypoglycemia. To learn more about one side effect in particular, head to our article: Are Headaches A Side Affect Of Ozempic?
Cost Difference Between Metformin and Ozempic
One major difference in medications that affects the rate at which they are prescribed is that metformin is significantly cheaper than Ozempic.
Based on prices from 2023, a one-month supply of metformin (60 tablets of 500 mg) has an average price of around $7, with a maximum price of around $22, and as cheap as $1.62 with a savings card. Due to this cheap price, metformin is usually prescribed as the first medication for new diabetes patients.
On the other hand, the average cost of Ozempic is roughly $916 or higher for a monthly supply without insurance. There are copay savings cards and other affordable options for those with insurance. You can find Ozempic for around $25 a month in the United States with insurance.
Rybelsus is slightly cheaper than Ozempic and can be found for roughly $10 with insurance. Wegovy is more expensive than both, with a monthly cost of roughly $1,349, but there are also saving options for that. These medications are much cheaper worldwide than in the United States, likely due to increased American demand.
You can learn more about semaglutide pricing in our article: How Much Is Semaglutide Without Insurance?
FAQs
In this section, we will answer some of the most common questions related to metformin vs. semaglutide.
Can januvia and ozempic be taken together?
Most doctors recommend against taking Januvia and Ozempic together because it can increase the risk of dangerously low blood sugar and side effects.
Can I take metformin and mounjaro together?
Yes, you can take metformin and Mounjaro together, however, most experts recommend against it. There are no drug interactions, but it can increase the risk of hypoglycemia and other side effects.
Is ozempic better than metformin?
Most people with diabetes start with metformin before trying Ozempic. However, when it comes to metformin or Ozempic for weight loss, Ozempic is significantly better.
What works better than semaglutide?
Mounjaro has been proven more effective than semaglutide on its own at weight management and improving glycemic control.
Will my doctor prescribe semaglutide for weight loss?
Yes, your doctor may prescribe any of the three brands of semaglutide drugs. Although Wegovy is the only semaglutide medication that is FDA-approved for weight loss, doctors often prescribe Ozempic and Rybelsus off-label for weight management.
What can I take instead of semaglutide for weight loss?
Other medications used for weight loss include Mounjaro (tirzepatide) and phentermine. There are also natural options such as berberine or natural fat burner supplements, as well as other diabetes medications.
Which Weight Loss Medicine Is Best For You?
Despite being diabetes medications, people commonly use both prescriptions for weight loss. Semaglutide medications like Ozempic directly stimulate insulin secretion to help stabilize blood sugar levels, whereas metformin affects insulin indirectly.
Metformin decreases glucose production in the liver, improves insulin sensitivity in the muscles, and improves glucose uptake by cells to lower blood sugar levels. Metformin is effective at treating diabetes despite not causing an increase in insulin-like semaglutide. Doctors typically start new diabetes patients on metformin due to its effectiveness and cheap cost.
Semaglutide is far more expensive than metformin but is also far more effective at weight loss. If weight loss is your primary goal and you have insurance or can afford it, I recommend Ozempic or another semaglutide product.
To learn more about how semaglutide stacks up to other similar medications, check out our articles comparing Liraglutide vs Semaglutide and Semaglutide vs Phentermine.
References:
- Mahapatra, Manoj Kumar, et al. “Semaglutide, a Glucagon-like Peptide-1 Receptor Agonist with Cardiovascular Benefits for Management of Type 2 Diabetes.” Reviews in Endocrine and Metabolic Disorders, vol. 23, no. 3, 7 Jan. 2022, https://doi.org/10.1007/s11154-021-09699-1.
- Nasri, Hamid, and Mahmoud Rafieian-Kopaei. “Metformin: Current Knowledge.” Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences, vol. 19, no. 7, 2014, www.ncbi.nlm.nih.gov/pmc/articles/PMC4214027. Accessed 7 Oct. 2023.
- Knowler, William C, et al. “Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin.” The New England Journal of Medicine, vol. 346, no. 6, 2002.
- Miles, Kaitlin E., and Jessica L. Kerr. “Semaglutide for the Treatment of Type 2 Diabetes Mellitus.” Journal of Pharmacy Technology, vol. 34, no. 6, 30 July 2018, https://doi.org/10.1177/8755122518790925.
- Ghusn, Wissam, et al. “Weight Loss Outcomes Associated with Semaglutide Treatment for Patients with Overweight or Obesity.” JAMA Network Open, vol. 5, no. 9, 19 Sept. 2022, p. e2231982, jamanetwork.com/journals/jamanetworkopen/fullarticle/2796491?resultClick=1, https://doi.org/10.1001/jamanetworkopen.2022.31982.
- Seifarth, C, et al. “Effectiveness of Metformin on Weight Loss in Non-Diabetic Individuals with Obesity.” Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [And] German Diabetes Association, vol. 121, no. 1, 2013, www.ncbi.nlm.nih.gov/pubmed/23147210, https://doi.org/10.1055/s-0032-1327734.
Kyle Ustach
Author