Berberine vs Metformin: Which Is Better For Diabetes? 

Doctors commonly prescribe the compound metformin in the treatment of diabetes.

Berberine is often used for the same condition in alternative medicine.

Is berberine good for diabetes? Healthcare providers and researchers alike often ask this question and compare these two substances.

Instead of looking at metformin vs berberine, what if we thought about using them together? Read on to find out why that may be a possibility (and an effective one at that!).

What is berberine?

Berberine is a Chinese herb. Its Latin name is Coptis chinensis. Berberine is also present in other herbs, including the plant barberry.

People in China have used berberine for diabetes for thousands of years. Berberine has a structure that we call an isoquinoline alkaloid extract.

Berberine supports healthy blood sugar levels as well as healthy heart function. People also use berberine for prediabetes, weight loss, and the treatment of polycystic ovary syndrome (PCOS).

What is metformin?

You may be asking yourself, “is berberine the same as metformin?” Metformin is a pharmaceutical synthetic compound. It comes originally from the French lilac.

Metformin was the first drug that was conventionally used for prediabetes and diabetes. Metformin helps to lower hemoglobin a1c.

It can also assist in weight loss, cancer prevention, and polycystic ovary syndrome. However, most of the research on metformin relates to its role in type 2 diabetes.

Metformin can be used alone. You can also combine it with insulin treatment or with an oral antidiabetic medicine called a sulfonylurea.

Metformin is only available with a prescription from a doctor.   Metformin does not help in type 1 diabetes because these people cannot produce insulin from their pancreas. Patients with type 1 diabetes usually control their blood glucose with insulin injections.

Metformin is also used in the treatment of PCOS. PCOS stands for polycystic ovary syndrome. This is a hormonal condition that affects ovulation and may increase androgen production. Androgens are male hormones responsible for facial hair growth and male pattern baldness.

PCOS increases the risk of developing obesity, depression, infertility, and type 2 diabetes.

How do they work?

Both metformin and berberine increase the activity of the AMPK enzyme. Our bodies activate this enzyme when there is an energy deficit (for example, during fasting or exercise).

Cells will activate the AMPK system to get better access to energy. This improves glucose and fatty acid uptake from the blood. It also increases the breakdown of glycogen and fat. It even prevents the storage of glucose and fat.

So how does AMPK do this? It acts in several different ways. One of these is by phosphorylating enzymes. This has an immediate effect. The other way is by phosphorylating enzyme transcription factors. This leads to a longer-lasting effect.

Both metformin and berberine can increase the body’s consumption of glucose. They can also both inhibit the first complex of the electron transport chain.

When they do this, the entire process becomes less efficient at producing ATP (adenine triphosphate). ATP is the source of energy in the body. As a result, the body will use energy in a way similar to that of a restricted-calorie diet or starvation mode.

Metformin

Metformin decreases the formation of new glucose in the liver (this is what we call gluconeogenesis).

Type 2 diabetes affects the way the body uses glucose as fuel. The two main causes of this are insufficient insulin production by the pancreas and poor cellular response to insulin.

Insulin is the hormone that tells the body’s cells to increase glucose uptake from the bloodstream. In type 2 diabetes, the poor insulin production and/or poor cellular response to insulin causes blood glucose levels to continue rising. This can continue until the circulatory, nervous, and immune systems become damaged.

The body has its own process for creating new glucose. This is gluconeogenesis, where the liver produces glucose from amino acids or lactate. Metformin can inhibit the process of gluconeogenesis. It does this by inhibiting metabolic complexes in the mitochondria of the cells.

Mitochondria have electron transport chains. These are in charge of generating energy. There are four protein complexes within the chain that release energy. They do this through a series of reactions.

Researchers used to think that metformin inhibited complex I. This is the first and biggest of all the energy-producing complexes. However, researchers now believe that metformin inhibits the mitochondrial enzyme glycerol 3-phosphate dehydrogenase (GPD2).

We now know through further investigations metformin actually works on the fourth complex of the mitochondrial electron transport chain, not the first. Metformin’s work on complex IV of the chain inhibits glycerol conversion to glucose and inhibits GPD2.

GPD2 catalyzes one of the steps in the process of converting glycerol to glucose through gluconeogenesis. Metformin is known to significantly reduce gluconeogenesis from glycerol.

This is significant because gluconeogenesis from glycerol is dysregulated in type 2 diabetes. This then leads to more glucose production in the liver. This is why metformin has more effect on lowering glucose in patients with type 2 diabetes than in those without.

Overall, metformin inhibits complex IV. This then inhibits GPD2. This prevents glycerol to glucose conversion, thus preventing high levels of gluconeogenesis in the liver.

Metformin can also prevent glycerol from becoming blood sugar. Glycerol is released when fat is broken down.

40 percent of blood sugar comes from glycerol! That is a significant portion. This is why glycerol is an important substrate to target in diabetes.

Berberine and blood sugar

Berberine appears to work its magic by improving insulin resistance. It increases the activity of the AMPK system and has anti-oxidant and anti-inflammatory properties.

These are two factors that can support managing type 2 diabetes. Berberine aids in the regulation of proinflammatory cytokines and oxidative stress indicators.

Berberine has been found to reduce oxidative stress and inflammation in tissues, according to research. Kidney tissue, adipose tissue, liver tissue, pancreatic tissue, and other tissues are examples.

One research looked at berberine in people with type 2 diabetes. It included 36 persons who had just been diagnosed with type 2 diabetes mellitus. They were given either berberine or metformin at 0.5 grams three times each day.

This was a three-month testing period. What were the outcomes? They discovered that berberine has the same blood sugar-lowering impact as metformin.

The use of berberine led to significant decreases in hemoglobin a1c, from 9.5% to 7.5%. Berberine lowered fasting blood glucose from 10.6 mmol/L to 6.9 mmol/L. Berberine lowered postprandial blood glucose from 19.8 mmol/L to 11.1 mmol/L.

There is also research to show that the therapeutic actions of berberine for diabetes may be due to its regulation of non-coding RNAs (ribonucleic acids). This can help prevent the progression of type 2 diabetes.

Berberine is also helpful through its anti-inflammatory activities. Research shows that berberine has a cytoprotective effect in the beta cells of the pancreas. It does this by slowing a metabolic pathway that causes inflammation.

Dosage of berberine and metformin for diabetes

Berberine

You may be wondering about berberine dosage for diabetes specifically. You might be saying, “how much berberine should I take for diabetes?”

A starting dose of berberine for blood sugar regulation is 500 milligrams. You would normally take this berberine dose for diabetes either at dinner or bedtime.

Your health care provider may increase your dose to 500 milligrams twice per day with meals. Some health care practitioners even use 500 milligrams three times per day.

Talk to your health care provider to see which dose is appropriate for you. Your body absorbs berberine more effectively when you take it with milk thistle. Therefore you may want to consider taking these two herbs together.

Metformin

A typical dose of metformin is 500 milligrams every 12 hours with food. Another option is 850 milligrams once a day with a meal. This dose would then increase every two weeks. Maintenance doses are usually around 1500 to 1550 milligrams per day orally.

How long does it take berberine vs metformin to work?

Berberine

So how quickly does berberine lower blood sugar anyway? Most studies looking at berberine are 90 days long. Therefore, it’s safe to say you can expect results within three months. However, some patients even say they get a blood sugar lowering effect in the first month of taking berberine.

Metformin

Metformin tends to work much more quickly than berberine. It usually takes four to five days to get the full benefit from your metformin medication. This does depend upon your dosage, however.

Comparing berberine vs metformin

Is berberine better than metformin? Many people think of berberine as an over-the-counter metformin substitute.

If you’re deciding whether to use metformin vs berberine to lower blood sugar, it may be good to perform a comparison here.

Berberine and metformin have similar effects on controlling hemoglobin a1c levels. They also have similar effects on fasting blood glucose levels and postprandial blood glucose levels (blood glucose concentrations after eating).

Berberine can reduce hemoglobin a1c from an average of 9.5 to 7.5. Glucocil is a berberine supplement. When glucocil and metformin are taken together, this has an additive effect. This means that hemoglobin a1c, fasting blood glucose, and postprandial glucose levels are lowered further.

Berberine was able to lower HOMA-IR, an indicator of insulin resistance. No research showed that metformin was able to do this.

Berberine also did not affect liver function tests.

Metformin reduces hemoglobin a1c, but in addition to this, it also lowers body weight. When it comes to berberine vs metformin for weight loss, metformin appears to come out on top. It also helps to reduce the risk of death from cardiovascular disease.

Both metformin and berberine support healthy blood sugar levels. They are actually similar in terms of their mechanisms of action and their effects on the body at a cellular level. Both metformin and berberine increase activity of the AMPK enzyme.

The benefits of berberine vs metformin

Berberine benefits for diabetes include the following. Berberine was able to lower both total and low-density lipoprotein (LDL) cholesterol. However, metformin does not have this same effect on cholesterol numbers.

Berberine also has anti-inflammatory and immune-supporting properties that do not appear to be present in metformin.

Metformin can be helpful for other illnesses aside from just type 2 diabetes. These include cardiovascular disease, aging, and certain types of cancer. It is not clear that berberine has the same effect on these conditions.

Side effects of berberine vs metformin

Metformin

The side effects of metformin include the following:

  • Nausea
  • Diarrhea
  • Bloating
  • Gas
  • Abdominal discomfort
  • Lack of appetite

It is important to note that these side effects are fairly common. They appear to be worse in patients who consume a large number of carbohydrates as part of their diet. These side effects have many takers of metformin asking themselves, “what is better than metformin?” Enter berberine.

Berberine

Berberine side effects include the following:

  • Diarrhea
  • Constipation
  • Flatulence
  • Abdominal pain

Though similar to those of metformin, these side effects were either just as severe or less severe than the side effects of metformin.

Can berberine replace metformin?

You may be wondering whether there are natural metformin alternatives. There is a study showing that berberine can replace metformin in part.

This would help to reduce the toxicity and side effects that we can see with a commercial drug such as metformin. Berberine may be a safe and healthy metformin substitute. This is why berberine is sometimes called a metformin supplement.

Are berberine and metformin safe to take long-term?

You may be asking yourself, “is berberine safe to take long-term?”

One retrospective investigation looked at berberine use over 12 months. Researchers concluded that berberine over the year was safe and well-tolerated by participants in the treatment groups of the study.

Researchers say that metformin use in diabetes is safe and well-tolerated. They say that it is durable for at least ten years of treatment! However, recent concerns have developed over the NDMA content of metformin. This is a carcinogen.

Can you take berberine and metformin together?

All this begs the question, “can you take berberine with metformin?” The short answer here is “yes.”

Research shows that the combination of berberine and metformin may enhance their hypoglycemic effects. In other words, these substances are not just additive but synergistic in their actions. In fact, berberine can improve the intestines’ ability to tolerate metformin treatment.

Conclusion

You now have a better idea of what berberine and metformin are. We hope that you have also gleaned from this article how berberine and metformin work inside the body.

This article has covered dosing, benefits, long-term safety, and side effects of these two substances. You also know more information about berberine as a possible metformin replacement and how they can work together.

If you are wondering whether metformin vs berberine or both are right for you, speak to your health care provider about these substances today.

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Sources

  1. Chang, W. (2017). Non-coding RNAs and berberine: A new mechanism of its anti-diabetic activities. Eur J Pharmacol. 15 (795), 8-12. https://pubmed.ncbi.nlm.nih.gov/27915042/ 
  2. Diabetes Prevention Program Research Group. (2012). Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care. 35 (4), 731-7. https://pubmed.ncbi.nlm.nih.gov/22442396/ 
  3. LaMoia, TE; Butrico, GM; Kalpage, HA & Shulman, GI. (2022). Metformin, phenformin, and galegine inhibit complex IV activity and reduce glycerol-derived gluconeogenesis. PNAS. 119 (10), e2122287119. https://pubmed.ncbi.nlm.nih.gov/35238637/ 
  4. Marazzi, G; Cacciotti, L; Pelliccia, F; Iaia, L; Volterrani, M; Caminiti, G; Sposato, B; Massaro, R; Grieco, F & Rosano, G. (2011). Long-term effects of nutraceuticals (berberine, red yeast rice, policosanol) in elderly hypercholesterolemic patients. Adv Ther. 28 (12), 1105-13. https://pubmed.ncbi.nlm.nih.gov/22113535/ 
  5. Prabhakar, PK & Doble, M. (2009). Synergistic effect of phytochemicals in combination with hypoglycemic drugs on glucose uptake in myotubes. Phytomedicine. 16 (12), 1119-26. https://pubmed.ncbi.nlm.nih.gov/19660925/ 
  6. Wang, L; Liu, D; Wei, G & Ge, H. (2021). Berberine and metformin in the treatment of type 2 diabetes mellitus: A systematic review and meta-analysis of randomized clinical trials. Health. 13 (11), epub. https://pubmed.ncbi.nlm.nih.gov/23118793/ 
  7. Zhu, X; Wei, Y; Yang, B; Yin, X & Guo, X. (2020). The mitohormetic response as part of the cytoprotection mechanism of berberine: Berberine induces mitohormesis and mechanisms. Mol Med. 26 (1), 10. https://pubmed.ncbi.nlm.nih.gov/31973689/ 

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