Berberine vs Metformin (Side Effects, Dosage, Benefits)

berberine vs metformin

Metformin is a commonly prescribed commercial pharmaceutical for individuals at risk for or who have developed type 2 diabetes.  While there are countless promising findings surrounding Metformin’s efficacy in blood glucose management, what about an option for those who practice more holistic forms of therapies? 

In recent years, Berberine has been gaining recognizable momentum within the medical field for treating type 2 diabetes.  Many have even begun claiming it the golden “Metformin alternative.” If you are someone looking for a natural solution to treating your blood sugar levels, Berberine is worth taking a deeper look into.

What Is Metformin?

Metformin was originally developed in Europe from natural compounds found in a plant called the French Lilac or Goat’s Rue, Galega officinalis

Its active ingredient, guanidine, was often used as an herbal remedy in the Middle Ages to treat symptoms of diabetes, such as excessive urination.

Throughout centuries of exploration, the pharmaceutical drug we are familiar with today, Metformin, was developed in 1992 and FDA-approved in 1994

Who should take Metformin? 

In modern-day medicine, Metformin is one of the first lines of defense in the management and treatment of type 2 diabetes. When combined with specific diet and exercise changes, it helps stabilize blood glucose (blood sugar) levels. 

Metformin also helps prevent diabetes in people at high risk for developing type 2 diabetes.

Additionally, Metformin is used to help treat or relieve symptoms from polycystic ovary syndrome (PCOS).

How does Metformin work?

Diabetes mellitus (DM) creates abnormally high glucose levels due to an insufficient amount of insulin being released, or an improper cellular response to insulin. 

insulin sensitivity

Metformin works by helping restore the body’s response to insulin. It does this in a variety of ways, including:

Insulin Sensitivity

  1. Increases sensitivity to insulin: Insulin is the hormone that helps move sugar from your bloodstream to your cells to give them energy. When there is an overload of sugar in the bloodstream, your cells stop efficiently responding to insulin as efficiently, which is known as insulin resistance.  Metformin helps decrease insulin resistance so your cells respond to insulin and can absorb and use sugar properly.

Improves Glucose Uptake

  1. Lowers glucose uptake: One major way sugar enters your body is through diet. During the digestive process, food is broken down and makes its way to the intestines, which is where sugar is absorbed into the bloodstream. Metformin helps limit the amount of sugar that’s absorbed in the intestines, thus limiting the amount of sugar that enters your bloodstream.

Lowers Glucose Production

  1. Lowers sugar production: Your body produces its own sugar by the liver through a process called glycogenolysis. Metformin helps lower the amount of sugar your liver makes.

What are the side effects of Metformin?

Metformin is generally prescribed for long-term use. Side effects are typically mild, but common. They include nausea, upset stomach, diarrhea, weakness, or a metallic taste in the mouth. 

Metformin does not usually cause hypoglycemia, however, low blood sugar levels can occur if it is used with other anti-diabetic drugs, including insulin and sulfonylureas (glyburide, glimepiride, glipizide) to treat diabetes.

Although rare, an allergic reaction or lactic acidosis (a buildup of lactic acid in the bloodstream) may occur.

What Is Berberine?

Berberine is a naturally occurring chemical found in numerous medicinal plants like European barberry, goldthread, and China Gold. 

what is berberine
European barberry

It contains many pharmacological properties such as antiviral, antidiarrheal, and antibacterial and has been used for centuries in Chinese and Ayurvedic medicine practices for various ailments, including digestive issues and infections.

European barberry

Recently, Berberine treatment has been pushed into the spotlight for its anti-diabetic activity and hypoglycemic effects in several type 2 diabetes clinical studies. 

When I worked for the Fond du Lac band of Ojibwa at the Care Clinic (Center for American Indian Resources), I had the pleasure of working with Dr. Lorraine Turner.

Dr. Turner, like the Native American people, prefers to use natural remedies, if and whenever able. 

I learned from Dr. Turner that Berberine can be used in conjunction with other diabetes treatments, including Metformin and insulin.

As an example, Dr. Turner and I shared a female patient in her mid 60s with type 2 diabetes. She started on Berberine, 500 mg, twice daily. She tolerated berberine treatment with minimal side effects, with some  mild abdominal pain. 

The patient’s blood glucose levels improved, including her postprandial blood glucose levels. She was delighted when I was able to significantly reduce her insulin dose.

We also noticed a decrease in blood pressure, as well as a decrease in total cholesterol.

Who should take Berberine?

Due to Berberine’s favorable effects against insulin resistance, it is popularly used among individuals with type 2 diabetes. 

Berberine is also an excellent form of therapy for individuals with metabolic syndrome, which includes the following symptoms: hypertension, high cholesterol, triglyceride abnormalities, abdominal obesity, and elevated blood sugar levels, all of which increase the risk of developing type 2 diabetes and heart disease.

Individuals who experience polycystic ovary syndrome (PCOS) also benefit from the use of Metformin, as it helps lessen the symptoms.

Berberine may also be useful for general health protection from high blood pressure, establishing healthful lipid parameters including total cholesterol and serum triglycerides, favoring weight loss, and promoting overall “anti-aging.”

How does Berberine work?

Like Metformin, Berberine’s primary mechanism is helping the body become more responsive to insulin and lower blood sugar levels. 

Several clinical studies have surfaced supporting its effectiveness to be comparable to Metformin. 

Berberine helps treat diabetes by:

  • Decreasing insulin resistance
  • Increasing the breakdown of sugar (glycolysis)
  • Decreasing sugar production by the liver (glycogenolysis)
  • Slowing the breakdown of carbohydrates in the gut

What are the side effects of Berberine?

Generally, Berberine appears to be safe and well tolerated. Possible side effects include abdominal pain, diarrhea, constipation, and/or flatulence. 

Like other medications or supplements, side effects of berberine usually occur within the first few weeks of starting. 

The severity of side effects may depend on your dosage, a combination of any other drugs you’re taking, or your own personal response to new therapies. Berberine may not act the same way in each individual. 

Clinical studies demonstrate Berberine may support healthy body function, however, more research is required to confirm the long-term safety and side effects of Berberine.  

How Does Berberine and Metformin Lower Blood Sugar?

Metformin and Berberine are found to help support healthful blood sugar levels. Both compounds do this by increasing the effects of insulin, aka they have been coined “insulin sensitizers”. 

how to lower blood sugar

They have identical effects on AMP-activated protein kinase, or AMPK.

AMPK is present in every cell and acts as a basic regulator of metabolism that facilitates the uptake of glucose. 

They both increase the activity of AMPK, thus slowing the metabolic pathway and leading to increased fat and glycogen breakdown, as well as decreased glucose and fat storage.

Berberine vs Metformin Recommended Dosage

Metformin Dosage

Metformin is a pharmaceutical drug that requires a prescription from your doctor or medical provider. Dosage varies depending on the strength, form, and brand of Metformin you are prescribed.

Metformin IR (Immediate release) is the standard prescription. Patients usually start with a 500 mg tablet, and increase their dose by 500 mg each week to goal. 

The maximum dose for Metformin IR is 2500 mg. People usually take this medication one to two times daily with meals, sometimes three times a day.

Popularly prescribed brands of Metformin include Glucophage, Glumetza, and Fortamet.

Metformin also comes in an extended release form, Metformin ER. The extended release form allows you to take your entire dose in one tablet, usually once per day.

Berberine Dosage

Berberine supplements are readily available in health stores and online for purchase without a prescription. 

Currently, there is no recommended dosage of Berberine, however, most studies administer 900-1500 milligrams per day with a typical regimen of taking 500 mg two or three times per day with meals.

Berberine has a half-life that spans over several hours, making it necessary to spread the dosage throughout the day. 

It is important to discuss options with your doctor or medical provider before purchasing Berberine supplements.

Comparing Metformin vs Berberine

When comparing Berberine and Metformin, studies have shown Berberine to exhibit equal effects on glucose metabolism and blood-sugar-lowering properties as Metformin.

  1. Both compounds help to lower several glucose and insulin indicators in individuals with type 2 diabetes, including fasting blood glucose (FBG), postprandial blood glucose (PBG), fasting insulin, and postprandial insulin. However, the most notable finding for both Berberine and Metformin is their identical ability to lower HbA1c up to 2 points with regular and dedicated use.

Which Has Higher Bioavailability? (Ability to be absorbed by the body)

Several factors can interfere with the rate at which a medication or supplement is absorbed and used within the body. 

Parameters such as forms of dosage, chemical properties, and gut health may all hinder bioavailability.  

Typically, many anti-diabetic medications have a lower bioavailability due to their high solubility and low permeability chemical makeup. 

Metformin is absorbed by the body at moderate rates with an absolute oral bioavailability of 40% to 60%.  

Berberine, on the other hand, has a rather unimpressive absolute oral bioavailability of less than 1%. This may be due to its hydrophilic (easily dissolves in water) structure and its inability to cross the plasma membrane lining of intestinal cells.

Approximately 56% of oral Berberine is not absorbed, and an additional 43.5% is lost due to metabolism in the intestines. 

However, studies are in the works for developing methods of increased absorption involving Milk Thistle, water-soluble derivatives, and encapsulation in nanotubes.

Additional Benefits of Berberine

Reduces Oxidative Stress

A buildup of chronic inflammation is the foundation of several diseases and illnesses. 

Reactive oxygen species (ROS) are key molecules that play an important role in the progression of inflammation.  ROS are produced by a molecule called nicotinamide adenine dinucleotide phosphate hydrogen (NADPH).

It has been found Berberine helps reduce oxidative stress and inflammation by inhibiting the expression of NADPH, thus reducing the production of ROS.    

Protects Against Bacterial Infections

In addition to the improvement in blood sugar levels, Berberine has anti-inflammatory and immune-supporting properties that do not appear to be present in Metformin. 

Due to this, Berberine has successfully been used in the treatment of bacterial and fungal infections.

Berberine allows for excess cholesterol to move to the liver for further processing and excretion, thus helping to lower low-density lipoprotein (LDL) cholesterol levels and increasing high-density lipoprotein (HDL) levels to prevent the risk of heart diseases and strokes and improving overall heart health.

Reduces High Cholesterol

Berberine allows for excess cholesterol to move to the liver for further processing and excretion. 

how to reduce cholesterol

This helps to lower low-density lipoprotein (LDL) cholesterol, or “bad” cholesterol levels and increasing high-density lipoprotein (HDL), or “good” cholesterol levels to prevent the risk of heart disease and stroke and to improve overall heart health.

Inhibits Cancer and Tumor Formation

Berberine has been found to stimulate mitochondrial apoptotic pathways, allowing increased apoptosis (cell death).

This behavior has been found to help patients with breast, lung, prostate, colorectal, and gastric cancer as a natural anti-carcinogen that prohibits tumor formation.

Is Berberine as Effective as Metformin

Several studies have shown Berberine to be comparably beneficial to lowering blood sugar as Metformin. 

A review of 14 studies found berberine to be equally effective at lowering blood sugar as commercial type 2 diabetes medications, including Metformin, Avandia, and Glucotrol.

Can Berberine and Metformin be taken together?

Research shows the synergistic actions of Berberine and Metformin when taken in combination may enhance blood sugar lowering effects. 

One thought behind this is Berberine’s ability to improve intestinal health for higher tolerance of Metformin treatment.

Can Berberine damage the liver?

There is currently no evidence that Berberine harms liver function tests and/or overall liver health.

Medical researchers have discovered Berberine may improve liver health and blood lipids in individuals with Non-Alcoholic Fatty Liver Disease (NAFLD) due to its impressive influence on lipid metabolism.  

Can Berberine damage the kidneys?

In a randomized controlled clinical trial with patients with diabetic nephropathy (damage to the kidneys), results demonstrated that berberine may improve diabetic nephropathy. 

Participants taking berberine for six months experienced significant improvements in two important markers for kidney function, including the albumin/creatinine ratio in urine. 

Can you substitute Berberine for Metformin?

Evidence suggests Berberine is a safe and powerful blood-sugar lowering herbal supplement that may be as effective as commercial type 2 diabetes drugs, such as Metformin. 

Furthermore, Berberine may be a promising blood-sugar lowering alternative for individuals who cannot take type 2 diabetes medications due to liver, kidney, or heart disease.

It is important to consult with your doctor or healthcare provider before taking berberine to discuss potential risks and/or drug interactions.

Is Berberine Safe To Take Long Term?

Several clinical investigations determined Berberine to be safe and well-tolerated for long-term use provided you do not have additional chronic medical conditions.  If the symptoms or side effects mentioned above are present, it is recommended to discontinue the use of Berberine and consult your doctor or health care provider immediately.

Can you Substitute Berberine for Metformin?

Pilot studies show that berberine produces results that are compatible to Metformin. If you are considering Berberine in place of Metformin, or adding Berberine to your current prescription plan, talk to your Medical providers or your diabetes care specialist to discuss what will work best for you.

How much will Berberine Lower my A1c?

Berberine is comparable to Metformin, in that it can lower A1c by about 2%. Berberine reduced triglycerides and total cholesterol, but it was not statistically significant. Further studies are needed. 

Is Berberine Intended for Long-term Use?

The berberine treatment trials lasted from a few weeks to up to 2 years, so no long-term studies have been done. However, people have taken berberine-rich plants for years, with no reported symptoms. It has long been used in traditional Chinese medicine, which supports long-term use. 

Berberine vs Metformin Conclusion

Berberine is a generally safe and well-tolerated herbal supplement with a plethora of noteworthy therapeutic benefits.  

Typically, Berberine is administered as an oral supplement and performs equivalently to commercial diabetes medications, such as Metformin, concerning hypoglycemic effects on type 2 diabetes.

Although its absorption level is limited, continuous clinical studies are being performed to further investigate Berberine’s full potential to be used as an herbal alternative to diabetic drug therapy.

Talk with your medical care provider or diabetes care and education specialist if you are interested in learning more.


Berberine vs. Metformin | Dr. Whitaker | Healthy Directions

Efficacy of Berberine in Patients with Type 2 Diabetes – PMC (

Metformin: Current knowledge – PMC (

A bird’s eye view on a therapeutically ‘wonder molecule’: Berberine – ScienceDirect

Side effects and benefits – Pros and Cons (

Berberine and Metformin for Longevity | Thrivous®

Diabetes and Berberine: Safety, Dosage, and Review (

Metformin (Oral Route) Proper Use – Mayo Clinic

Metformin: historical overview | SpringerLink

Berberine vs Metformin: Which Is Better For Diabetes? (

Berberine vs Metformin – RENUE BY SCIENCE – Bioavailable NAD+ Boosters

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