Key Points

• Ozempic (semaglutide) and metformin are both used to treat type 2 diabetes, but they have not been directly compared in clinical trials.
• Both medications lower hemoglobin A1C levels by a similar percentage in separate studies.
• The choice between Ozempic and metformin depends on factors such as administration method, side effects, and cost.
• Ozempic is brand-name only, while metformin is available in generic versions, making it more affordable.

Mechanism of Action: How Ozempic and Metformin Work Differently

Ozempic (semaglutide) and metformin both help manage blood sugar levels but work in different ways:

Metformin

Metformin is a biguanide that is taken by mouth up to a few times daily. It works in different ways to manage blood glucose levels:

• Reduces glucose production in the liver
• Improves insulin sensitivity
• Slows down absorption of glucose from the intestines

Ozempic

Ozempic (semaglutide) is an injectable GLP-1 receptor agonist, meaning it mimics a naturally occurring hormone in your body called glucagon-like peptide-1. It is injected under the skin once a week. It works by:

• Stimulating insulin release to lower blood sugar
• Slowing digestion, increasing fullness and reducing appetite

How Effective Are Metformin and Ozempic?

Though no direct comparison studies exist, separate trials show both medications effectively lower hemoglobin A1C (HbA1c) levels:

• Ozempic lowered HbA1c by 1.4-1.6% over 30 weeks (study of 388 patients).
• Metformin lowered HbA1c by 1.4% over 29 weeks (study of 286 patients).

Individual responses vary based on dose, lifestyle, and concurrent medications.

Comparing Weight Loss: What Clinical Studies Show

Neither Ozempic nor metformin are FDA-approved for weight loss, but both have been associated with modest weight reduction. Both Ozempic and metformin can support weight loss, but studies show Ozempic generally leads to more significant results.

Metformin and Weight Loss

Experts classify metformin as a weight-neutral treatment option for patients with type 2 diabetes. It has the potential to cause a small amount of weight loss in some patients.

• Patients lost 0.6 kg (1.4 lbs) in a 29-week clinical trial.
• Another study showed a 2.9 kg (6.4 lbs) loss over five years.

Ozempic and Weight Loss

Because Ozempic slows down how fast food moves through your digestive tract, it can decrease your appetite and result in lower calorie consumption. This can lead to weight loss in some patients.

In a 30-week study:

• Ozempic 0.5 mg users lost 3.8 kg (8.3 lbs).
• Ozempic 1 mg users lost 4.7 kg (10.3 lbs).
• Placebo users lost 1.2 kg (2.6 lbs).

In major trials, people using Ozempic with diet and exercise lost an average of 14.9–17.4% of their body weight over 68 weeks—far exceeding typical results with metformin alone, which often yield more modest weight reductions.

Weight loss with Ozempic is seen in people with type 2 diabetes, as well as those without diabetes but who are overweight or obese. In contrast, metformin tends to have mild-to-moderate effects on weight, with greatest benefit among those with insulin resistance or polycystic ovary syndrome (PCOS)

Patient Suitability: Which Medication for Whom?

Metformin is commonly recommended as a first-line therapy for most adults newly diagnosed with type 2 diabetes, thanks to its long track record, safety profile, low risk of causing low blood sugar, and affordability. Patients with moderate kidney disease, liver issues, or at risk for lactic acidosis may require closer monitoring or alternatives.

Ozempic is usually added when blood sugar remains high despite metformin, or for people who would benefit from greater weight loss or cardiovascular protection (such as those with existing heart disease) or kidney protection (those with chronic kidney disease). Ozempic is generally not given to people with a history of certain thyroid cancers or pancreatitis.

Related questions

• Mounjaro vs Ozempic: Which is right for you?
• Ozempic Side Effects to Watch For
• What are the long-term side effects of Ozempic?

Can You Take Metformin and Ozempic Together?

Yes. Studies show no interaction between the two medications. Since they work differently, they are often prescribed together for better blood sugar control. It’s becoming increasingly common to combine Ozempic with metformin, as their complementary mechanisms may deliver greater blood sugar reduction and enhanced weight loss.

Healthcare providers typically start with metformin, add Ozempic if needed, and encourage patients to maintain regular communication about side effects or changes in health status. Therapy is individualized and patients are closely monitored for gastrointestinal side effects and hypoglycemia.

During clinical studies submitted to the FDA for approval, some patients with type 2 diabetes took both Ozempic and metformin. If your blood sugar is not well controlled with one medication alone, your healthcare provider may recommend adding on another medication.

Side Effects of Metformin and Ozempic

Both medications commonly cause gastrointestinal side effects. Additionally, metformin can raise the risk for lactic acidosis. Some patients have reported pancreatitis while taking Ozempic.

Common Side Effects of Metformin (>5%)

• Diarrhea
• Nausea/vomiting
• Excessive gas
• Feeling weak
• Indigestion
• Stomach discomfort
• Headache

Common Side Effects of Ozempic (≥5%)

• Nausea
• Vomiting
• Diarrhea
• Stomach pain
• Constipation

Serious Risks

• Metformin: Risk of lactic acidosis (rare but serious condition).
• Ozempic: Reports of pancreatitis, gallbladder disease, and ileus in some users.
• Both drugs may cause hypoglycemia when used with other diabetes medications.

Below is a comparison table of side effects typically seen with Ozempic and metformin.

Side Effect	Metformin	Ozempic
Nausea	26%	16%
Diarrhea	53%	9%
Constipation	Rare	5%
Vomiting	26%	5%
Abdominal Pain	6%	7%

Cost Comparison and Insurance

For cost-sensitive patients, metformin is often available for as little as $4–$15/month as a generic. Ozempic, being brand-only, usually costs $850–$1,100/month without insurance, though copay assistance programs and insurance coverage can lower out-of-pocket expenses to $25–$45 monthly in some cases. Coverage and eligibility may vary by country, insurance plan, and clinical indication.

Key Takeaways

Ozempic and metformin are both effective for type 2 diabetes, but they work differently. Metformin is usually the first-line treatment due to its long-standing safety profile and affordability, while Ozempic may be considered when additional blood sugar or weight management is needed.

This is not all the information you need to know about metformin and Ozempic for safe and effective use and does not take the place of talking to your doctor about your treatment. Review the full product information here, and discuss this information and any questions you have with your doctor or other health care provider.

References

1. Fornes, A., Huff, J., Pritchard, R. I., & Godfrey, M. (2022). Once-Weekly Semaglutide for Weight Management: A Clinical Review. The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians, 38(4), 239–246. https://doi.org/10.1177/87551225221092681
2. Hausner, H., et. al. (2017). Effect of Semaglutide on the Pharmacokinetics of Metformin, Warfarin, Atorvastatin and Digoxin in Healthy Subjects. In: Clinical Pharmacokinetics. DOI: https://doi.org/10.1007%2Fs40262-017-0532-6
3. Kahn, S. E., et. al. (2006). Glycemic Durability of Rosiglitazone, Metformin, or Glyburide Monotherapy. In: The New England Journal of Medicine. DOI: https://doi.org/10.1056/nejmoa066224
4. Metformin [package insert]. (Updated 01/2023). ScieGen Pharmaceuticals Inc. Accessed 07/04/2024 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4e4c4ba9-65c6-4273-8f6b-2423ab521dad
5. Ozempic [package insert]. (Updated 09/2023). Novo Nordisk. Accessed 07/04/2024 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=adec4fd2-6858-4c99-91d4-531f5f2a2d79
6. Van Gaal, L., et. al. (2015). Weight Management in Type 2 Diabetes: Current and Emerging Approaches to Treatment. In: Diabetes Care. DOI: https://doi.org/10.2337/dc14-1630
7. Walling, A. D. 2003. Metformin for polycystic ovary syndrome. AAFP. https://www.aafp.org/pubs/afp/issues/2003/1201/p2265a.html

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