Berberine vs Metformin: How Do Their Benefits Compare?

• The Contenders|
• How They Compare|
• Side Effects|
• Accessibility and Usage|
• Which Is Right for You?|

When it comes to managing blood sugar, two names are creating buzz:

1. Metformin: The trusted prescription drug
2. Berberine: The ancient herbal supplement gaining fame as “nature’s Ozempic”

As a practitioner of functional medicine, I frequently work with clients who prefer natural or herbal approaches—leaning toward the berberine side of the berberine vs metformin equation. But I totally appreciate that for some people—especially those with type 2 diabetes—a prescription for metformin from their conventional doctor is the best course of action.

Both metformin and berberine have beneficial effects. In this article, we’ll explore their differences to help you determine which option might be the best fit for your own health journey.

Meet the Contenders: Berberine vs Metformin

One is a pharmaceutical mainstay, and the other is steeped in history. Both hold promise for type 2 diabetes and related metabolic issues. First, we’ll take a closer look at metformin before turning our attention to berberine.

What Is Metformin?

Metformin has been the backbone of type 2 diabetes management for decades. It’s also used for gestational diabetes—temporary diabetes during pregnancy. Part of the biguanides class of medications, it brings down blood sugar levels through a triple mechanism 1:

• Reducing glucose production by the liver
• Limiting glucose absorption in the intestines
• Enhancing insulin sensitivity (how effectively the body responds to insulin)

This multi-pronged action helps safeguard against the serious complications associated with prolonged high blood sugar levels. These include cardiovascular disease, nerve damage, vision problems, and skin sores or infections 2.

Benefits Beyond Diabetes

Metformin has also shown benefits for other conditions. For instance, it’s often prescribed off-label for polycystic ovary syndrome (PCOS), a common hormonal condition that affects how the ovaries work and makes it harder to get pregnant.

The lower insulin levels created by metformin help decrease levels of luteinizing hormone and testosterone that have become too high 1. This can help PCOS symptoms and improve fertility.

Some metformin users also find they lose some weight when taking metformin, likely due to its effects on glucose metabolism. However, the drug does not cause significant body weight loss and is not a weight-loss medication 1.

What Is Berberine?

Berberine is a plant-based alkaloid (bitter substance containing nitrogen) used in traditional Chinese medicine 3. Berberine occurs naturally in a variety of different herbs 4, such as barberry and Coptis chinensis (Chinese goldthread).

Traditionally, people have used berberine for wound healing, digestive complaints, and toothaches, as well as fevers and inflammatory conditions 4 5. Research supports that the alkaloid may have anti-inflammatory, antioxidant, anti-microbial, and anti-cancer properties 4 5.

Berberine’s Affects on Metabolic Health

In modern times, berberine has gained recognition for its potential to regulate blood sugar levels and improve metabolic health.

Berberine can improve insulin sensitivity by activating AMP-activated protein kinase (AMPK) and SIRT1, enzymes that play a key role in regulating energy usage 6 7. 

Clinical studies highlight the efficacy of berberine in managing blood sugar.

Specifically, a meta-analysis of 20 randomized controlled trials compared berberine and placebo for effects on blood sugar. It found that on average, 900–2,400 mg/day of berberine for 1–6 months reduced 8:

• Fasting blood glucose levels by 9.4 mg/dL
• HbA1c (a measure of average blood sugar level over the past two to three months) by 2.6% 
• Fasting insulin by 2.36 mU/L

The effects were larger in women, those with type 2 characters, and Asians.

In addition to supporting blood sugar control, berberine has shown potential for:

• Reducing total cholesterol, LDL cholesterol, and triglycerides 9
• Improving intestinal health by fostering a balanced gut microbiome
• Reducing markers of inflammation in humans 10

It is also used for broader applications like tackling metabolic syndrome and supporting weight loss.

How Do Berberine and Metformin Compare?

Guidance from a trusted health practitioner will help you make the best decision when choosing between berberine and metformin. However, conducting your own research is equally valuable. Let’s break down the key aspects of berberine vs metformin and see how the two approaches compare.

Blood Sugar Management

When it comes to managing blood sugar, berberine and metformin are both highly effective. In fact, we have some quality data that directly compare the two. The research in question—a meta-analysis of 46 clinical studies—involved over 4,000 people with type 2 diabetes. It found that 7:

• Berberine and metformin were equally effective at lowering blood glucose. 
• Berberine had better effects than metformin on three separate measures of blood sugar control—HbA1c, fasting plasma glucose, and 2-hour plasma glucose.

The bottom line? Berberine and metformin are effective for managing type 2 diabetes, with berberine sometimes outperforming metformin in specific measures. This is likely due to the additional anti-inflammatory qualities of berberine, which may slightly enhance its impact on reducing HbA1c compared to metformin 10. 

However, metformin is a standardized medicine that is regulated by the FDA and has a clearly defined dosing regime. Berberine is sold as a supplement with less standardization and less clear evidence as to the correct dosage.

If you are looking to use berberine to treat a medical condition like type 2 diabetes it’s essential that you get your physician’s advice and choose an appropriate product and dosage.

Weight Loss and Obesity

Berberine and metformin may contribute to minor weight loss through managing blood sugar, and some other distinct mechanisms. However, neither is a top-tier weight loss solution. And despite the nickname “nature’s Ozempic”, berberine is also not as effective as the GLP-1 hormone-mimicking class of weight loss drugs.

Animal studies suggest that berberine 6 11:

• Increases fatty acid oxidation, a process that encourages fat loss
• Boosts heat production and energy expenditure (calorie burn)

However, berberine’s impact on weight in humans is minimal. According to an umbrella meta-analysis (strong evidence), over 17,000 participants taking 770–1,600 mg of berberine for 2–6 months lost just 2 lbs on average 12.

Meanwhile, metformin may modestly reduce weight by regulating blood sugar and by stimulating the production of an appetite-suppressing substance in the intestine 13  People with prediabetes who took metformin lost an average of 4.6 lbs over 3 years (compared to negligible weight loss in a placebo group). 

However, those who made lifestyle changes instead, including regular exercise, lost a lot more weight—on average 12.4 lb 14.

In summary, improving blood sugar control—which both metformin and berberine excel at—means both can manage weight to a minor degree.

However, diet and lifestyle changes remain far more effective for achieving significant weight loss. Pairing either berberine or metformin with a diet and exercise plan can greatly enhance weight loss outcomes. 

PCOS and Hormonal Benefits 

Both metformin and berberine can be helpful remedies for women with PCOS. 

Metformin is commonly prescribed to regulate menstrual cycles and address insulin resistance, a hallmark of PCOS.

Meanwhile, berberine slightly outperforms metformin in reducing elevated testosterone levels in PCOS 6. Many of my female clients have found a berberine-containing formula very useful for regulating irregular cycles.

In fact, for PCOS, it may not be a question of berberine vs metformin but rather berberine plus metformin. According to one meta-analysis, using the two together led to a very significant decrease in testosterone levels (11.5 ng/dL) 15.  

Cholesterol and Cardiovascular Health

Taking metformin reduces cardiovascular events (such as a blood clot, heart attack, or irregular heartbeats) in people with type 2 diabetes or coronary artery disease 16 17. But for lowering cholesterol levels, berberine takes the lead.

A meta-analysis involving nearly 1,800 participants shows that 900–1,500 mg/day of berberine for 1–6 months 9:

• Reduced total cholesterol and LDL cholesterol by 18 mg/dL 
• Reduced triglycerides by 13 mg/dL
• Increased HDL cholesterol (the good type of cholesterol) by 2.3 mg/dL

Impressively, berberine can reduce cholesterol about as well as the statin drug simvastatin, and it can reduce triglycerides slightly more. 

Combining berberine with simvastatin can reduce the debilitating side effects of statins, like liver enzyme increases and muscle pain. But it may cause more cases of constipation 18.

Gut Health

Metformin’s gastrointestinal side effects include diarrhea, nausea, and vomiting, limiting its appeal for those with sensitive stomachs 1. 

Berberine can also cause some GI symptoms 12. However, it also has the potential to significantly improve intestinal health. At the clinic, we use berberine’s antimicrobial qualities to help people with lingering gut sensitivities and troublesome dysbiosis (gut microbiota imbalance).

Animal studies suggest that berberine may balance gut bacteria and increase populations of friendly Lactobacilli bacteria 19.

IBS

In humans, a study showed berberine may help people with irritable bowel syndrome (IBS) have 20:

• Fewer episodes of diarrhea
• Reduced abdominal pain and urgency
• Improvements in anxiety and depression symptoms 

The study in question showed these benefits in people who took 800 mg/day of berberine for two months. It’s worth noting the study only involved 96 people so more comprehensive data is needed. 

SIBO

A current study is looking at how berberine compares to rifaximin, a prescription antibiotic, for treating symptoms of small intestine bacterial overgrowth (SIBO). We already have clients with SIBO who have found berberine helpful, but it’s good this is being investigated scientifically.

Earlier research found that a combination herbal formula containing berberine worked as well as the antibiotic rifaximin for resolving SIBO. This current research will find out if berberine on its own is just as effective 21. 

Colon Health

Berberine might also lower the risk of colorectal adenoma (colon or rectal polyp) recurrence. In a meta-analysis, recurrence was 31% lower in those taking berberine—a promising finding for long-term colon health 22.

What About Side Effects?

Neither option is completely free of side effects but they differ in their impact.

Metformin

The most common side effects of metformin are nausea, diarrhea, and vomiting 1. Other side effects related to metformin can include:

• Chest discomfort
• Headache
• Sweating more than usual
• Low blood sugar
• Weakness
• Runny, stuffy, itchy nose or sneezing

In rare cases, metformin can contribute to lactic acidosis, a dangerous rise in blood acidity. Long-term use may also contribute to vitamin B12 deficiency. 

Berberine

Berberine can cause GI side effects like flatulence and abdominal discomfort but the effects tend to be milder. Side effects become more noticeable at doses above 300 mg/day 12 23. 

Constipation is the most common side effect of berberine we come across in the clinic. A higher fiber diet and staying well hydrated can help to combat this downside.

Accessibility, Cost, and Usage

Metformin is an affordable and widely available FDA-approved drug, especially in its generic form. On the other hand, over-the-counter berberine supplements can vary significantly in quality and cost.

A key recommendation is to look for berberine supplements that are:

• Third-party tested
• Manufactured to good manufacturing practice (GMP) guidelines to ensure safety and efficacy

These aren’t necessarily the most expensive—you can likely get a good supplement for $1 a day.

At the clinic, we use berberine in the form of berberine hydrochloride (HCl). While this has relatively poor bioavailability, it’s the best-studied form (and there are no data demonstrating our bodies need a more bioavailable form) 24 25. We also don’t know how different berberine formulations or forms might affect health.

Our recommendations for the use of berberine HCl with our clinic clients are as follows:

• Dose
  • Take 770–2,400 mg/day of berberine HCl 9 10 12 26 spread over two to three doses with food
• Duration
  • Up to 12 months is safe (we need more research to know about longer durations)

Which One Is Right for You?

Choosing between berberine vs metformin will depend on your individual health goals and should be a decision you make in conjunction with your doctor or other key healthcare provider.

As a very rough rule of thumb:

• Berberine may appeal if you prefer a natural remedy with benefits for cholesterol, gut health, and inflammation. It could also be ideal for managing prediabetes, metabolic syndrome, or blood sugar levels.
• Metformin could be the choice for you if you need a reliable, prescription-strength treatment for type 2 diabetes mellitus or PCOS, especially when blood sugar control is the primary goal.
• In some cases, combining the two may offer complementary benefits—enhancing glucose metabolism, reducing insulin resistance, and supporting overall metabolic health.

Berberine vs Metformin: A Personal Decision

Whether you lean toward the pharmaceutical power of metformin or the natural wisdom of berberine, taking care of your metabolic health is a positive step. Prioritizing balanced blood sugar levels can have a lasting impact on your overall well-being.

If you would like to take a more natural or integrated approach to your health issues, one of our experienced functional health practitioners can help—just reach out using our website. We can work with you to achieve better overall health via diet, supplements, and other natural means. However, we will always advise when we feel conventional approaches, e.g., metformin for blood sugar control, are best.

The Ruscio Institute has also developed a range of high-quality formulations to help our clients and audience If you’re interested in learning more about these products, please click here. Note that there are many other options available, and we encourage you to research which products may be right for you The information on DrRuscio.com is for educational purposes only It is not a substitute for professional medical advice, diagnosis, or treatment.