top of page

Berberine, the Natural Alternative to Metformin?

Written by Trang Tran, Pharm.D. Candidate | Reviewed by Dr. Amy Knaperek, Pharm.D.

Type 2 diabetes is one of the most common chronic diseases and remarkably, there are more than 415 million people with diabetes in the world and the number will be 642 million by 2040. Unfortunately, diabetes is a risk factor for cardiovascular disease, chronic kidney disease, and is associated with many other health complications. Thus, controlling blood sugar level in people with diabetes will help reduce morbidity and mortality.

Despite the availability of blood-sugar lowering medications, adverse effects or subsequent failure after long-term use of these medications may limit the treatment of diabetes. Unlike some botanical products that are mixtures of multiple compounds which makes it difficult to control their quality, berberine is a single purified compound that has been shown to exhibit blood sugar-lowering effect and anti-obesity effect in humans and lab studies.

What is berberine?

Berberine was used in Chinese and Ayurvedic medicine around 3000 B.C. It is the main active component of a Chinese herb Coptis chinensis French, which has been used to treat diabetes for thousands of years. Interestingly, berberine is an over-the-counter drug that is used to treat gastrointestinal infections in China. Not only is berberine usually used as an antibiotic drug for diarrhea in China, but recent studies have reported that berberine may also play a role in lowering blood sugar and cholesterol.

What is the role of berberine in type 2 diabetes?

A pilot study was conducted in Chinese subjects for three months to determine the efficacy of berberine in the treatment of patients with type 2 diabetes. The first part of the study aimed at comparing berberine with metformin (Glucophage), and the second part of the study aimed at evaluating the additive or synergistic effects of berberine on the classical anti-diabetic agents (i.e., combination therapy). Compared to metformin, berberine demonstrated the same effect since it significantly decreased the hemoglobin A1c or HbA1c (which reflects the average blood sugar level over the past 3 months), fasting blood sugar, and postprandial blood sugar. However, triglycerides and total cholesterol were significantly lower in the berberine group compared to the metformin group. Hence, berberine demonstrated its advantage of synergistic effect on both sugar and cholesterol metabolism. In the combination therapy, the addition of berberine reduced HbA1c, fasting blood sugar, and postprandial blood sugar. Additionally, triglyceride, total cholesterol, and low density lipoprotein (LDL-C) were significantly lower than baseline. Moreover, the waist and waist/hip declined significantly.

Furthermore, a systematic literature review and meta-analysis of trials that were conducted among Chinese patients with type 2 diabetes suggests that berberine or berberine combined with oral blood-sugar lowering agent has a significant blood-sugar lowering effect, which appeared to be similar to the effect of oral blood-sugar lowering agent in patients with type 2 diabetes.

A meta-analysis of 21 clinical trials demonstrated the therapeutic effect of berberine in type 2 diabetes, high cholesterol, and high blood pressure. Notably, increased blood sugar, high cholesterol, and high blood pressure are crucial risk factors for cardiovascular diseases.

A systematic literature review found that berberine with lifestyle intervention was more effective in lowering the level of HbA1c than lifestyle intervention alone or placebo.

How does berberine work?

Anti-Diabetic Action

Berberine serves as an insulin sensitizer because it upregulates the insulin receptor expression. In an animal model, berberine has been shown to reduce insulin resistance, and in liver, fat, and muscle cells, berberine has been shown to increase sugar uptake in the absence of insulin. Additional antidiabetic actions of berberine include increasing secretion of insulin and decreasing inflammation. Furthermore, berberine may act as an alpha-glucosidase (an intestinal enzyme that is responsible for digesting ingested carbohydrates) inhibitor, thereby decreasing sugar absorption in the gut.

Cardiovascular Protective Action

By upregulating the LDL receptor gene expression, berberine may help lower LDL-cholesterol (which is commonly known as the “bad” cholesterol).

Anti-Obesity Action

Berberine has been shown to downregulate the generation of fat cells and fatty acids, thereby suggesting its potential role in treating obesity.

Because berberine reduces alanine and aspartate transaminase (these are the enzymes in the liver that are elevated when the liver is damaged) levels in patients with type 2 diabetes, it may indirectly suppress non-alcoholic fatty liver disease.


Clinical studies have evaluated berberine at dosages ranging from 500 mg to 1500 mg per day for as long as 6 months. In one study, berberine 500 mg was taken three times daily at the beginning of each major meal.


Berberine is generally well-tolerated, but adverse effects may include diarrhea, constipation, flatulence, and abdominal pain. The gastrointestinal side effects of berberine may be attributed to its mode of action of inhibiting sugar absorption in the gut.

In the aforementioned pilot study, no significant changes in liver and kidney functions were observed with berberine treatment. Because some first-line drugs for type 2 diabetes are not recommended in the case of liver dysfunction, kidney disease, and heart disease, the safety record of berberine seems promising.

Of note, berberine can interact with prescription drugs. Please consult with your healthcare provider before starting berberine.

The Bottom Line

The benefits of berberine in lowering blood sugar, cholesterol, body weight, and blood pressure as well as its minimal side effect profile render it a possible drug candidate in the treatment of type 2 diabetes. However, further long-term studies with a larger sample size are needed to confirm the therapeutic effect and safety of berberine in other ethnic groups with type 2 diabetes.


  1. Alpha-glucosidase. Alpha-Glucosidase - an overview | ScienceDirect Topics. Accessed February 22, 2022.

  2. Chang W, Chen L, Hatch GM. Berberine as a therapy for type 2 diabetes and its complications: From mechanism of action to clinical studies. Biochem Cell Biol. 2015;93(5):479-486. doi:10.1139/bcb-2014-0107

  3. Dong H, Wang N, Zhao L, Lu F. Berberine in the treatment of type 2 diabetes mellitus: a systematic review and meta-analysis. Evid Based Complement Alternat Med. 2012;2012:591654. doi:10.1155/2012/591654

  4. Liang Y, Xu X, Yin M, et al. Effects of berberine on blood glucose in patients with type 2 diabetes mellitus: a systematic literature review and a meta-analysis. Endocr J. 2019;66(1):51-63. doi:10.1507/endocrj.EJ18-0109

  5. Wang H, Zhu C, Ying Y, Luo L, Huang D, Luo Z. Metformin and berberine, two versatile drugs in treatment of common metabolic diseases. Oncotarget. 2017;9(11):10135-10146. Published 2017 Sep 11. doi:10.18632/oncotarget.20807

  6. Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008;57(5):712-717. doi:10.1016/j.metabol.2008.01.013

  7. Zhang H, Wei J, Xue R, et al. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Metabolism. 2010;59(2):285-292. doi:10.1016/j.metabol.2009.07.029

  8. Zhang Y, Li X, Zou D, et al. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab. 2008;93(7):2559-2565. doi:10.1210/jc.2007-2404

  9. Image link:

114 views0 comments


bottom of page