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Berberine vs. Metformin: Can One Replace the Other?

Inadequate management of weight and blood sugar can escalate into chronic illnesses, such as diabetes. To address these concerns, medications like metformin and berberine are commonly employed for weight loss and blood sugar regulation. If you're seeking to regulate your blood sugar and weight effectively, you might be pondering over which compound suits you best. This article highlights the disparities between berberine and metformin, encompassing their uses, side effects, benefits, and associated risks.

How does berberine work?

Berberine is a natural supplement that has been used in Eastern medicine for centuries. More recently, berberine has been highlighted for its role in blood sugar control and weight management.

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Berberine targets an enzyme called AMP-activated protein kinase (AMPK). This enzyme is involved in the regulation of cellular carbohydrate and fat metabolism. Berberine’s chemical structure is different from medications used to lower blood glucose. Here are some of the ways that berberine impacts blood sugar and body weight:

  • May improve insulin sensitivity. Insulin is a hormone that helps the body turn glucose from the blood into energy that can be used by the cells. Without insulin, sugar in the blood is unable to enter the body’s tissues. When you have insulin resistance, your cells are unable to respond to insulin normally, and extra sugar stays in the blood.
  • May improve glucose metabolism. In other words, it may help your cells use glucose better. If your cells can use sugar from your blood more efficiently, it will lower your blood glucose levels. The exact method by which berberine affects glucose metabolism is still under investigation.
  • May decrease glucose production in the liver. In addition to helping your body use the glucose in your blood effectively, it decreases the amount of sugar created by your liver. Less glucose production means less sugar is released into your blood.

Side effects of berberine

Since berberine is a natural supplement that is not regulated by the FDA, it has not undergone the same type of intensive safety trials as metformin and other medications. People who have used berberine report stomach pain, diarrhea, and constipation.

Metformin and its mechanism of action

Metformin is a prescription medication that is part of a drug class called biguanides. It uses a combination of methods to regulate blood sugar. Let’s explore each method separately.

  • Decreases the amount of glucose produced by the liver. The liver normally produces glucose based on the amount available in the blood. Less sugar released into the bloodstream by the liver means there will be less glucose circulating in the blood.
  • Decreases the amount of glucose that is absorbed in the digestive system. There is more information needed about how metformin decreases glucose absorption, but there are scientific findings that suggest metformin potentially impacts how the colon interacts with glucose.
  • Improves the amount of glucose that body tissues receive and use. This decreases the amount of circulating blood glucose. Constant elevation of sugar in your bloodstream is dangerous and can cause great harm to many bodily organs like your kidneys and eyes, as well as damage your nerves and blood vessels.

Side effects of metformin

Metformin is mostly safe to use. The most common side effects of metformin are related to the digestive tract. Diarrhea, nausea, and vomiting affect 30% of people who take metformin. Metformin can also cause a rare but serious side effect called lactic acidosis in which low blood pH can lead to respiratory emergencies and feelings of fatigue.

Berberine and metformin for different purposes

Berberine has been shown to decrease blood sugar, cholesterol, and weight gain in people with type 2 diabetes. In addition to decreasing blood sugar, metformin has also been shown to regulate fat metabolism. Let’s go into more detail on each of the many different ways berberine and metformin are used.

For blood sugar control

Metformin and berberine have been shown to lower blood sugar in people with or without type 2 diabetes.

Metformin is FDA-approved to lower blood sugar in type 2 diabetes. It currently comes in two types of tablets: immediate release and extended release. Metformin can cause stomach upset and diarrhea, so doses are typically started at 500 mg or 1,000 mg twice daily and increased slowly each week. For type 2 diabetes, the usual maintenance dose of the immediate release tablet is 850 mg or 1,000 mg twice daily. The extended release tablet dosing is usually 2,000 mg taken once or twice daily.

It is also the only medication recommended by the American Diabetes Association for pre-diabetes. If you have pre-diabetes, it means your fasting blood sugar is higher than normal, but not high enough for you to be diagnosed with diabetes. Prevention of type 2 diabetes is an off-label use of metformin, and the typical dosing for pre-diabetes is 850 mg twice daily.

Berberine may reduce inflammation, improve insulin sensitivity of fat tissue, and reduce fat tissue within the body. In one study comparing 36 people taking either berberine or metformin, berberine reduced fasting blood glucose, blood glucose after eating, and HbA1c. Please remember that berberine is not an FDA-approved medication. Although the results from smaller studies like this one are promising, more clinical research in larger groups of people is needed.

Berberine has been studied at various doses in multiple smaller clinical trials. The doses include 200 mg to 400 mg three times daily, 500 mg two to three times daily, and 1,000 mg three times daily for blood sugar control. If you're interested in using berberine to control your blood sugar, you should talk with your physician about which dose is appropriate for you.

For weight loss

Both metformin and berberine have been shown to provide weight loss benefits. Metformin has not been FDA-approved for weight loss, but studies show that people taking metformin daily were able to lose a moderate amount of weight over time. And although berberine is a natural supplement that is not regulated by the FDA, smaller studies also show that it may lead to a decrease in weight or a slimming of the waist.

One study included people with obesity without diabetes and found that people taking 2,550 mg of metformin daily lost about 13 pounds over 28 weeks. In another study of people who were at high risk for type 2 diabetes, participants lost about 4 pounds (2.1k g) and 3.5% of their body mass after using metformin. The weight loss continued with long-term use. Other than stomach upset and diarrhea, metformin was used safely for at least 10 years.

Metformin may be an option to help you lose weight whether you have diabetes or not. If your doctor recommends that you take metformin to help with weight loss, remember that it’s important you continue to take the medication consistently for the best results.

Berberine has also been studied in relation to obesity and excessive fatty tissue within the body. One study examined weight loss benefits in 100 women with polycystic ovarian syndrome and showed that people who took berberine had a significant reduction in the width of their waist, with or without a decrease in weight.

If you are looking to lose excess weight, you should ask your doctor whether metformin or berberine is a good fit for your situation.

For anti-aging

Metformin is being studied for its anti-aging benefits and has been shown to activate AMPK and extend the life span of rodents. Studies on the anti-aging effects of metformin in humans are currently ongoing, so there are still more things that need to be researched. The TAME (Targeting Aging with Metformin) Trial, currently exploring metformin use to target aging in individuals aged 65–79 over a 6-year time frame, and the MILES (Metformin In Longevity Study) Trial are looking into metformin’s ability to delay the progression of age-related diseases.

Berberine has also been studied for its effects on skin aging and life span. Its activation of AMPK has been shown to protect cells from oxidative stress damage and boost overall health in mice. It has not been reported that berberine increases life span in humans.

Other ways you can use berberine and metformin

Metformin is used off-label for polycystic ovarian syndrome (PCOS). For PCOS, the immediate release form of metformin is typically used starting at 500 mg once or twice daily. Every week, the dose is increased by 500 mg. Metformin should only be used for PCOS under the guidance of a physician. If you currently have PCOS and are interested in taking metformin, please talk with your doctor to see if this medication is a good option for you.

The effects of berberine on fertility and the number of live births for women with PCOS have been studied. A recent review on berberine supplementation in women with PCOS concluded that berberine improved the insulin resistance in theca cells with an improvement of the ovulation rate per cycle; this suggests that berberine can be effective in fertility and live birth rates.

If you have PCOS and are looking to become pregnant, you may consider talking to your doctor about adding berberine to your supplement regimen.

Can you take berberine with metformin?

Berberine and metformin have been studied in combination for decreasing blood sugar levels. Studies have shown berberine can help reduce stomach discomfort and diarrhea caused by metformin. It was also shown that when taken together, these medications decrease blood sugar more than they do when taken alone.

If you are interested in taking berberine and metformin together, you should talk to your physician about making safe adjustments to your metformin dose and whether or not adding berberine is a good option for you.

Switching one with the other: is it safe?

If you have been diagnosed with type 2 diabetes, your physician may prescribe metformin as part of your treatment regimen with or without berberine. You should not try to manage your diabetes on your own without your physician. Since metformin is an FDA-approved medication and berberine is a supplement, you will need a prescription to start metformin, but berberine will not require a prescription.

If you are already taking metformin and considering switching to berberine, please do not do so without the guidance of your physician. Metformin should never be stopped abruptly as doing so may cause metformin withdrawal symptoms. Also, since berberine's safety has not been studied in large clinical trials approved by the FDA, your doctor may not agree that berberine is the best option for you.

If you have not been diagnosed with type 2 diabetes and want to lose weight or maintain your blood sugar levels in a healthy range, you may consider berberine as a supplement to help.

In any case, you should always talk with your doctor before starting any new medications or supplements.

Metformin and berberine alternatives

If you're unable to take metformin or berberine, you should discuss other options for managing your blood sugar levels with your physician. Several medications for blood sugar control are available as injections, but there are prescription medications and non-prescription supplements available as tablets or capsules that your doctor may consider.

One drug alternative to metformin is a category of medications called thiazolidinediones. They are a class of prescription drugs that are FDA-approved for lowering blood sugar in people with type 2 diabetes. They work by increasing the body’s sensitivity to insulin.

Alternatives for berberine include inositol and cinnamon supplements. Inositol is not FDA-approved, but it has been shown to mimic insulin in the body and decrease blood glucose levels after eating. Cinnamon supplements are being studied for their ability to help with glucose control in type 2 diabetes when added to other medications. Studies show that cinnamon moderately reduces fasting blood glucose levels with doses ranging from 120 mg to 6,000 mg per day taken between 4 and 16 weeks when combined with current blood glucose-lowering medications. Larger studies are needed to determine if the addition of cinnamon has a meaningful effect on blood glucose control.

In the end, metformin and berberine are two completely different compounds for blood sugar management. Metformin requires a prescription, has been well studied, and is FDA-approved for lowering blood glucose levels. On the other hand, berberine is a natural supplement that does not require a prescription. Berberine has only been studied in smaller populations and is not FDA-approved. Both metformin and berberine have been shown to provide weight loss benefits. If you are considering using metformin or berberine for blood glucose control or weight loss, you should talk to your doctor first to determine the best solution for you.


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