Updated: Nov 20, 2025, 3:37pm

Metformin vs Semaglutide: Weight Loss, PCOS, Side Effects, Cost

Written By Stephanie Wright

Registered Nurse & Health Writer

Dr. Hirenkumar Italia

Expert Review | Board-Certified Family Physician

Content

Quick Answer: Metformin vs Semaglutide

Category	Metformin	Semaglutide (Ozempic/Wegovy/Rybelsus)
Class/Mechanism	Biguanide; lowers liver glucose production, improves insulin sensitivity	GLP-1 receptor agonist; increases insulin secretion, reduces appetite, slows digestion
Indications	Type 2 diabetes, insulin resistance, PCOS (off-label)	Type 2 diabetes (Ozempic/Rybelsus), chronic weight management (Wegovy)
Typical Weight Loss	~ 3% of body weight	~10–15% of body weight
Common Side Effects	GI upset, diarrhea, B12 deficiency	Nausea, vomiting, constipation, delayed gastric emptying
Serious Risks	Rare lactic acidosis (Boxed Warning)	Pancreatitis, gallbladder disease, retinopathy warning, thyroid C-cell tumors (rodent data)
Form	Oral tablet (generic)	Weekly injection / daily oral tablet
Cost (2025)	$4–$30 per month generic	Metformin generic often $4–$30/mo; Ozempic historically ~$900–$1,000 list but select $499/mo DTC cash options emerged in 2025; coverage varies; Rybelsus: ~ $984.58
Who It Fits	Low-cost first-line T2D or PCOS management	Clinically meaningful weight loss or T2D with cardiovascular risk

Updated November 2025

CTA: Start your telehealth intake—see if you qualify for semaglutide or tirzepatide.

Bottom line: Health experts find people lose more weight on average. Doctors often use metformin to treat insulin resistance and support people with Polycystic Ovarian Syndrome (PCOS).

How They Work (Mechanisms & Indications)

When comparing metformin vs semaglutide, it helps to first understand how each works. Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist. The goal is to simulate the hormones of the gut to:

Trigger the pancreas to release insulin when glucose rises
Block the liver’s release of glucose
Slows stomach emptying
Reduces appetite

Ozempic and Wegovy are weekly injectables. Rybelsus is the only daily oral GLP-1 pill right now. Semaglutide and other GLP-1s can treat type 2 diabetes and chronic weight management.

Metformin works differently. It’s a biguanide class of medication that hinders glucose production in the liver and increases insulin sensitivity. Metformin has long been regarded as the first-line therapy for type 2 diabetes and often prescribed off-label to treat PCOS-related insulin resistance.

Doctors only recently started to prescribe semaglutide and other GLP-1 drugs to help people with type 2 diabetes or obesity achieve meaningful weight loss and improve heart health. But they’ve relied on metformin as a foundational treatment for diabetes for decades.

Metformin vs Semaglutide Weight Loss: What to Expect (Timelines & Percentages)

When comparing metformin vs semaglutide weight loss, the results change over time:

Semaglutide: A recent study of adults taking semaglutide 2.4 mg weekly lost about 15% of their body weight in 68 weeks, compared to 2% with placebo. More than half lost at least 15% of their weight.
Metformin: In the Diabetes Prevention Program (DPP), approximately 29% of people taking metformin lost at least 5% of their weight, compared to 63% in the lifestyle group and 13% in the placebo group. Over the long term (years 6–15), those on metformin maintained a weight loss of approximately 6% of their starting weight—more than the lifestyle or placebo groups.
Combination therapy: Early evidence suggests that taking metformin with semaglutide may improve outcomes in people with insulin insulin resistance.

CTA: Prefer double-digit weight loss? Start a telehealth evaluation for semaglutide.

Metformin vs Ozempic for PCOS

Health guidelines recommend lifestyle management as a precedent over medication therapy. But, you can follow it with metformin if you’re a woman with a BMI greater than or equal to 25 and other symptoms. The drug works to improve insulin sensitivity while also helping restore regular menstrual cycles. Metformin remains the first-line metabolic therapy.

Emerging studies suggest that adding semaglutide to metformin enhances:

Weight loss
Insulin resistance
Reproductive outcomes

All of this is compared to taking metformin alone for PCOS. But GLP-1s, like Ozempic, remain off-label treatment only for PCOS. Any decisions should be made with an OB-GYN or endocrinologist before beginning therapy to stay safe.

CTA: Chat with a clinician about whether semaglutide is appropriate off-label for PCOS-related weight concerns.

Side Effects & Safety: Metformin vs Semaglutide

Semaglutide (Ozempic/Wegovy/Rybelsus)

Thyroid C-cell tumor warning: Animal studies suggest that semaglutide may increase the risk of thyroid tumors. Avoid taking it if you or a family member has a history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN 2).
Pancreatitis risk: Listen to your body for persistent, severe abdominal pain, as it may be a sign of pancreatitis (inflammation of the pancreas).
Retinopathy warning: Rapid improvement in blood sugar levels may worsen diabetic retinopathy in individuals with a history of the condition.
Gallbladder events and delayed gastric emptying: The slower digestion can impact how your body absorbs oral medications.
Common side effects: Nausea, vomiting, constipation, abdominal pain

Clinical takeaway: When comparing the side effects of metformin vs semaglutide, know that both require routine monitoring. Semaglutide might be a bit tougher on the body with the added endocrine and gallbladder precautions. In contrast, metformin requires kidney and B12 monitoring. You and your healthcare provider can work together to see which risk profile fits your health status.

Metformin

Boxed Warning: Lactic acidosis is a rare but serious side effect of metformin. It occurs more often in people with kidney problems or respiratory conditions.
Vitamin B12 deficiency: Low vitamin B12 levels are sometimes a result of taking metformin. Your healthcare provider will likely monitor your levels and prescribe a supplement, if needed.
Common side effects: Indigestion, upset stomach, metallic taste

Takeaway: Both medications are generally safe when taken as prescribed. Your healthcare provider may assess your pancreas and thyroid health before starting therapy with semaglutide. They may also check your kidney function and B12 levels with metformin use.

Cost & Coverage: Cost of Ozempic vs Metformin

Metformin (generic): Widely available for $4-$30 per month. The price depends on the formulation, insurance coverage, and any applicable coupons.
Ozempic (semaglutide): The list price ranges from $900 to $1,000. However, there are select cash-pay and DTC programs that are likely more budget-friendly. Insurance coverage varies depending on your diagnosis, health, and plan of care.
Rybelsus (oral semaglutide): The advertised price is currently around $984.

CTA: Check eligibility — our intake reviews coverage and cash-pay options and can prescribe semaglutide or tirzepatide when appropriate.

Metformin vs Ozempic: Which Is Better?

When deciding metformin vs Ozempic which is better, think about your health goals:

For weight loss: Semaglutide tends to deliver the most noticeable results. Studies show it can help people lose around 10–15% of their body weight, far more than what’s typically seen with metformin.
For cost and simplicity: Metformin is the clear winner. It’s affordable, widely available, and easy to take as part of a daily routine.
For PCOS management: Lifestyle changes—like balanced eating, regular exercise, and stress control—remain the first and smartest step. Adding metformin can further support hormone balance and insulin sensitivity. Some people may also benefit from a GLP-1 if weight or metabolic issues continue.
For type 2 diabetes with heart concerns: GLP-1 medications have shown strong evidence of lowering cardiovascular risk, making them a great choice for people managing both diabetes and heart health.

Bottom line: Semaglutide helps you lose weight faster with better results. But metformin is reliable and budget-friendly for people living with PCOS and insulin resistance.

CTA: Answer a few questions — get a personalized plan and see if you qualify for semaglutide or tirzepatide.

How to Start Safely (Screening, Titration, Follow-Up)

If you’re considering starting metformin vs semaglutide, you need to know what to expect in terms of dosing and monitoring.

Semaglutide Titration

Semaglutide therapy begins at a low dose and then increases gradually each month. The goal is to lessen the side effects as you progress. With each dose, you can still expect some discomfort like nausea and constipation. Typically, side effects subside within a month or two.

Metformin Initiation

Metformin comes in an extended-release tablet to deliver the medication gradually into the body. It’s best when taken with meals to improve tolerance and reduce side effects. Your healthcare provider may need to monitor your vitamin B12 levels and kidney function while using it.

Lifestyle Pairing

Both medications may cause stomach upset. The best way to curb the discomfort from the dual therapy is:

Eating protein-rich meals
Getting adequate fiber daily
Drinking at least 8-10 glasses of water daily
Perform a mix of strength training and cardio exercises to boost results

CTA: Start your telehealth intake—meet a clinician, get labs ordered if needed, and begin evidence-based dosing.

Frequently Asked Questions (FAQs)

1. Is metformin or semaglutide better for weight loss?

Semaglutide works better for weight loss than metformin. In studies, people taking semaglutide 2.4 mg weekly lost about 15% of their body weight in 68 weeks, while those on metformin lost around 5–6% on average. Metformin can still be helpful for those living with insulin resistance. Early research also suggests that combining it with other medications may enhance results for some people.

2. Can I take metformin and Ozempic together?

Yes! Combination therapy is a promising option to help treat your type 2 diabetes. It’s also increasingly used off-label for PCOS to boost weight loss and insulin resistance.

3. What are the biggest risks?

Semaglutide: pancreatitis, gallbladder disease, retinopathy warning. Metformin: B12 deficiency and rare lactic acidosis.

4. How much do Ozempic and metformin cost?

Metformin: $4–$30 with coupons. Ozempic: DTC cash options are available for around $499 (2025) for eligible patients.

5. Is Ozempic approved for PCOS?

Not yet. Ozempic is not FDA-approved for PCOS. However, metformin is approved.

Ready to talk? Complete your secure intake—OnlineSemaglutide.org can prescribe semaglutide or tirzepatide when clinically appropriate.