Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form.
Subscribe to the Magazine for free
Subscribe for free to keep reading! If you are already subscribed, enter your email address to log back in.
Thanks for subscribing!
Oops! Something went wrong while submitting the form.
Are you a healthcare practitioner?
Thanks for subscribing!
Oops! Something went wrong while submitting the form.

Berberine Vs. Metformin: The Similarities and Differences You Should Know

Medically reviewed by 
Berberine Vs. Metformin: The Similarities and Differences You Should Know

Diabetes impacts nearly 12% of adults in the United States, and approximately of the population is affected by metabolic syndrome. Given the widespread prevalence of these conditions and growing concerns related to pharmaceutical side effects, natural treatment alternatives are gaining popularity. 

Berberine, a vibrant yellow, plant-derived compound, has emerged as a promising alternative to metformin, a commonly prescribed medication for diabetes and related metabolic disorders.

This article offers a detailed comparison of berberine and metformin, highlighting their mechanisms of action, efficacy, potential side effects, and implications for patient care.


Berberine and Metformin: An Overview

Let's get to know Berberine and Metformin on a deeper level:


Berberine is a bioactive compound primarily extracted from the Berberis (barberry) genus of plants. Used traditionally for millennia across different cultures, berberine-rich plants are renowned for their therapeutic properties and applications in a wide range of health issues, including diarrhea, infections, inflammatory diseases, respiratory conditions, and more.

Ongoing clinical studies have emphasized berberine's antioxidant, anti-inflammatory, and immune-modulating properties, demonstrating great potential in regulating blood sugar and lipids, inhibiting cancer cell growth, and supporting a healthy gut microbiome

Researchers are also investigating its possible role in autoimmune diseases, neurodegenerative disorders, depression, and hormonal imbalances such as polycystic ovary syndrome (PCOS).


Metformin is an anti-diabetic drug used as the first-line treatment for type 2 diabetes (T2DM). Beyond its role in T2DM, metformin has numerous off-label indications, including:

Ongoing research is also exploring metformin’s potential roles in aging, cancer, and neurological health.

Mechanisms of Action

Berberine and Metformin have a lot in common but plenty of differences, too. Here is an overview of both:


Both berberine and metformin activate AMP-activated protein kinase (AMPK), an enzyme that regulates cellular energy balance. This has several beneficial effects:

  • Enhances glucose uptake in the muscles, liver, and fat cells.
  • Improves insulin sensitivity, aiding glucose entry into the cells and lowering blood sugar levels.
  • Decreases glucose production in the liver.
  • Improves the breakdown of fats for energy, a process that occurs in the mitochondria.

Additionally, both compounds reduce intestinal absorption of glucose. Emerging evidence also suggests that both berberine and metformin may benefit the gut microbiome, hormone balance, inflammation, and cancer prevention.


It is estimated that up to 75% of individuals with T2DM also have hyperlipidemia. While research suggests that metformin therapy alone has positive effects on lipid profiles, some evidence shows that berberine may offer superior results by way of several potential mechanisms:

  • Increasing LDL receptor (LDLR) activity in the liver to remove LDL (“bad”) cholesterol from the blood.
  • Decreasing the production of proprotein convertase subtilisin/kexin type 9 (PSCK9), a protein that degrades LDLRs. By reducing PSCK9, berberine helps maintain more active LDLRs, thereby lowering cholesterol levels in the blood.
  • Preventing excessive fat accumulation in the blood by reducing the activity of lipoprotein lipase, an enzyme that breaks down fats.

Other notable differences include:

  • Their structure– Whereas berberine is a more complex, plant-derived isoquinoline alkaloid, metformin is a synthetic biguanide compound with a simpler structure.
  • Metformin exhibits superior oral bioavailability compared to berberine.
  • While metformin should be avoided in individuals with liver or kidney disease, berberine may exert protective effects on these vital organs.

Efficacy in Managing Type 2 Diabetes and Metabolic Syndrome

Studies comparing berberine and metformin interventions in T2DM patients report no significant differences in their efficacy for reducing fasting glucose, postprandial glucose, or hemoglobin A1c (HbA1c) levels. However, combining the interventions significantly improves these parameters compared to metformin alone while also reducing the incidence of adverse events.

Additionally, berberine may be more effective than metformin in controlling lipids, with short-term studies showing notably lower levels of triglycerides and total cholesterol. Similar effects are observed in PCOS, another metabolic condition. 

Recent research indicates that berberine may offer more significant cardiovascular disease risk reduction compared to metformin in this patient population. 

This is attributed to its impact on body composition, lipid profiles, and hormonal improvements, including reduced waist size, waist-to-hip ratios, total cholesterol, triglycerides, low-density lipoprotein (LDL), and increased high-density lipoprotein (HDL) and sex hormone binding globulin (SHBG) levels.

Side Effects and Safety Profile

Berberine and Metformin have similar side effects and safety profiles. However, here are the specifics you should know:


The most common potential side effects of berberine are gastrointestinal in nature:

Avoid combining berberine with cyclosporine. Other possible drug interactions include:

  • Dextromethorphan, a cough medicine
  • Anti-diabetic drugs, including metformin
  • Anti-hypertensive drugs, including losartan
  • Anticoagulants/antiplatelet drugs
  • Sedative medications, including midazolam and pentobarbital
  • Tacrolimus, an immunosuppressive drug
  • Any medication that is a substrate of the following cytochrome P450 enzymes: CYP2C9, CYP2D6, or CYP3A4

Berberine use is contraindicated in:

  • Pregnant and breastfeeding women, due to berberine’s uterine-stimulating effects.
  • Infants, as berberine can cause or worsen jaundice and result in kernicterus, a life-threatening condition that causes brain damage.


Common side effects of metformin that affect up to 30% of individuals include:

  • Diarrhea
  • Nausea 
  • Vomiting

Rare side effects:

Contraindications to metformin use:

Cost, Accessibility, and Patient Preference

​​Several factors can impact the choice between berberine and metformin. While berberine typically costs less than metformin, insurance coverage for natural alternatives is often lacking, varying based on individual policies. 

Additionally, obtaining high-quality berberine supplements can be challenging due to issues like poor bioavailability and consumer confusion when navigating the vast dietary supplement market to find an effective product. 

Furthermore, given the often more favorable side effect profiles of natural alternatives like berberine, patients may prefer these options over synthetic treatments like metformin.

Can Berberine and Metformin Be Taken Together?

Evidence supports the safety and efficacy of combining berberine and metformin compared to using either agent alone. It is speculated that their combination may allow for lower dosages of each compound, addressing concerns such as berberine’s poor oral bioavailability and minimizing side effects associated with each substance used separately. 

However, comprehensive studies with larger sample sizes and of longer duration are necessary to fully understand their benefits as a combination therapy.


Key Takeaways

Berberine and metformin are effective options for managing metabolic conditions like type 2 diabetes, metabolic syndrome, and polycystic ovary syndrome, primarily through their shared mechanism of activating AMPK. 

While both interventions demonstrate comparable effects on glucose control, berberine may offer potential advantages in lipid management and cardiovascular risk reduction.

Healthcare providers should stay informed on the latest research and actively engage in open discussions with patients, sharing the benefits and potential risks of each therapeutic option. 

By customizing treatment plans according to each individual’s unique needs and preferences, providers can ensure the delivery of safe and optimal care.

The information provided is not intended to be a substitute for professional medical advice. Always consult with your doctor or other qualified healthcare provider before taking any dietary supplement or making any changes to your diet or exercise routine.
Learn More
No items found.

Lab Tests in This Article

No items found.

Achuff, J. (Ed.). (2024, February 6). How to Lower Your Patient’s Triglycerides Using Root Cause Medicine. Rupa Health.

Ataei, S., Prashant Kesharwani, & Amirhossein Sahebkar. (2022). Berberine: Ins and outs of a nature-made PCSK9 inhibitor. EXCLI Journal, 21, 1099–1110.

Athyros, V. G., Doumas, M., Imprialos, K. P., Stavropoulos, K., Georgianou, E., Katsimardou, A., & Karagiannis, A. (2018). Diabetes and lipid metabolism. Hormones, 17(1), 61–67.

Bertagna, B. (2024, February 29). The Role of Berberine in Restoring Hormonal Balance in PCOS. Rupa Health.

Blake, K. (2023, November 14). Integrative Strategies for Neurodegenerative Disease Management. Rupa Health.

Centers for Disease Control and Prevention. (2022, October 25). By the numbers: Diabetes in America. Centers for Disease Control and Prevention.

Chen, S., Gan, D., Lin, S., Zhong, Y., Chen, M., Zou, X., Shao, Z., & Xiao, G. (2022). Metformin in aging and aging-related diseases: clinical applications and relevant mechanisms. Theranostics, 12(6), 2722–2740.

Cleveland Clinic. (2022, November 23). Metabolic Acidosis: Causes, Symptoms, Diagnosis & Treatment. Cleveland Clinic.

Cleveland Clinic. (2023, June 13). Lactic Acidosis: Symptoms, Causes, Treatment & What It Is. Cleveland Clinic.

Cloyd, J. (2023a, March 8). Butyrate 101: Everything You Need to Know About This Short Chain Fatty Acid. Rupa Health.

Cloyd, J. (2023b, June 28). Complementary and Integrative Medicine Options for Patients With Liver Disease: Comprehensive Lab Testing, Nutrition, and Supplement Suggestions. Rupa Health.

Cloyd, J. (2023c, July 20). A functional medicine PCOS protocol: Comprehensive testing, therapeutic diet, and supplements. Rupa Health.

Cloyd, J. (2023d, July 28). A Functional Medicine Diarrhea Protocol: Comprehensive Lab Testing, Therapeutic Diet, and Supplements. Rupa Health.

Cloyd, J. (2023e, November 13). The Anti-Inflammatory Lifestyle: From Diet to Mindfulness. Rupa Health.

Cloyd, J. (2023f, December 19). How to Interpret Your Creatinine Blood Test. Rupa Health.

Cloyd, J. (2024a, January 2). A Functional Medicine Approach to Prediabetes. Rupa Health.

Cloyd, J. (2024b, January 17). Testing Your Patient's Hemoglobin A1c Levels: A Crucial Tool for Diabetes Management. Rupa Health.

Cloyd, J. (2024c, January 25). What is the Gut Microbiome? Rupa Health.

Cloyd, J. (2024d, March 1). What is Hyperlipidemia? Symptoms, Testing, and Treatments. Rupa Health.

Cloyd, J. (2024e, March 5). How to Lower LDL Cholesterol Naturally: Evidence-Based Recommendations. Rupa Health.

Cloyd, J. (2024f, March 6). How to Increase HDL Cholesterol: A Root Cause Medicine Approach. Rupa Health.

Cloyd, K. (2023, December 19). How to interpret your lipid panel results. Rupa Health.

Corcoran, C., & Jacobs, T. F. (2023, August 17). Metformin.; StatPearls Publishing.

Cross, L. V., & Thomas, J. R. (2020). Safety and Efficacy of Dietary Supplements for Diabetes. Diabetes Spectrum, 34(1), 67–72.

Daglis, S. (2024a, February 21). Decoding the Glucose Level in Your Basic Metabolic Panel. Rupa Health.

Daglis, S. (2024b, March 12). Emerging Therapies for Lipid Disorders: PCSK9 Inhibitors and Beyond. Rupa Health.

DeCesaris, L. (2023, July 18). Mitochondria - What They Are, Why We Should Care, and How to Support Them Using Functional Medicine Strategies. Rupa Health.

Ezzamouri, B., Rosario, D., Bidkhori, G., Lee, S., Uhlen, M., & Shoaie, S. (2023). Metabolic modelling of the human gut microbiome in type 2 diabetes patients in response to metformin treatment. Npj Systems Biology and Applications, 9(1), 1–8.

Gao, Y., Nie, K., Wang, H., Dong, H., & Tang, Y. (2024). Research progress on antidepressant effects and mechanisms of berberine. Frontiers in Pharmacology, 15.

Garrison, K. (2024, April 5). Luteinizing Hormone Function: Key Player in Reproductive Health. Rupa Health.

Gillani, S., Ghayedi, N., Roosta, P., Seddigh, P., & Nasiri, O. (2021). Effect of Metformin on Lipid Profiles of Type 2 Diabetes Mellitus: A Metaanalysis of Randomized Controlled Trials. Journal of Pharmacy and Bioallied Sciences, 13(1), 76.

Guo, H.-H., Shen, H.-R., Wang, L.-L., Luo, Z.-G., Zhang, J.-L., Zhang, H.-J., Gao, T.-L., Han, Y.-X., & Jiang, J.-D. (2023). Berberine is a potential alternative for metformin with good regulatory effect on lipids in treating metabolic diseases. Biomedicine & Pharmacotherapy, 163, 114754–114754.

Henry, E. (2022, January 4). How To Reverse Weight Gain And Slowed Metabolism. Rupa Health.

Johns Hopkins Medicine. (n.d.). Rhinitis.

Khakham, C. (2023a, March 28). An integrative medicine approach to kidney disease. Rupa Health.

Khakham, C. (2023b, April 6). Understanding Your Risk of Cardiovascular Disease With Functional Medicine Labs. Rupa Health.

Kim, J., Yang, G., Kim, Y., Kim, J., & Ha, J. (2016). AMPK activators: mechanisms of action and physiological activities. Experimental & Molecular Medicine, 48(4), e224–e224.

Koppen, L. M., Whitaker, A., Rosene, A., & Beckett, R. D. (2017). Efficacy of Berberine Alone and in Combination for the Treatment of Hyperlipidemia: A Systematic Review. Journal of Evidence-Based Complementary & Alternative Medicine, 22(4), 956–968.

Lan, J., Zhao, Y., Dong, F., Yan, Z., Zheng, W., Fan, J., & Sun, G. (2015). Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. Journal of Ethnopharmacology, 161, 69–81.

Lin, H., Ao, H., Guo, G., & Liu, M. (2023). The Role and Mechanism of Metformin in Inflammatory Diseases. Journal of Inflammation Research, Volume 16, 5545–5564.

Loan, A., Syal, C., Lui, M., He, L., & Wang, J. (2023). Promising use of metformin in treating neurological disorders: biomarker-guided therapies. Neural Regeneration Research, 19(5), 1045–1055.

Maholy, N. (2023, May 23). A Functional Medicine Treatment Protocol for Metabolic Syndrome: Testing, Nutrition, and Supplements. Rupa Health.

Manikandan, P., & Nagini, S. (2018). Cytochrome P450 Structure, Function and Clinical Significance: A Review. Current Drug Targets, 19(1).

Mishra, N., Verma, R., & Jadaun, P. (2022). Study on the Effect of Berberine, Myoinositol, and Metformin in Women with Polycystic Ovary Syndrome: A Prospective Randomised Study. Cureus, 14(1).

National Center for Complementary and Integrative Health. (2023, June). In the News: Berberine. NCCIH.

National Heart, Lung, and Blood Institute. (2022a, March 24). Heart Failure - What Is Heart Failure? | NHLBI, NIH.

National Heart, Lung, and Blood Institute. (2022b, May 18). Metabolic Syndrome - What Is Metabolic Syndrome? | NHLBI, NIH.

National Library of Medicine. (2024, February 22). Berberine: MedlinePlus Supplements.

Neag, M. A., Mocan, A., Echeverría, J., Pop, R. M., Bocsan, C. I., Crişan, G., & Buzoianu, A. D. (2018). Berberine: Botanical Occurrence, Traditional Uses, Extraction Methods, and Relevance in Cardiovascular, Metabolic, Hepatic, and Renal Disorders. Frontiers in Pharmacology, 9(557).

Neibling, K. (2023, February 27). Integrative Medicine Treatment for Headaches. Rupa Health.

Och, A., Och, M., Nowak, R., Podgórska, D., & Podgórski, R. (2022). Berberine, a Herbal Metabolite in the Metabolic Syndrome: The Risk Factors, Course, and Consequences of the Disease. Molecules (Basel, Switzerland), 27(4), 1351.

Orbeta, R. (2022, June 6). 10 Type 2 Diabetes Risk Factors You May Not Know About. Rupa Health.

Preston, J. (2022, November 10). What’s The Difference Between Good And Bad Dietary Fat? Rupa Health.

Preston, J. (2023a, July 3). Integrative Medicine and Gestational Diabetes: A Multidisciplinary Approach to Management. Rupa Health.

Preston, J. (2023b, September 22). Addressing Inflammation in Chronic Diseases: A Functional Medicine Perspective. Rupa Health.

Stanford, J. (2024, March 19). Exploring the Link Between Insulin Resistance and Obesity. Rupa Health.

Sweetnich, J. (2023a, March 10). Are Your Supplements Making You Constipated? Rupa Health.

Sweetnich, J. (2023b, March 13). Are Your Supplements Causing Diarrhea? Rupa Health.

Sweetnich, J. (2023c, April 25). Complementary and Integrative Medicine Approaches to Type 2 Diabetes Management. Rupa Health.

Sweetnich, J. (2023d, April 26). Unlocking the Benefits of Vitamin B12: The Importance of Maintaining Optimal Levels. Rupa Health.

Sweetnich, J. (2023e, May 19). Overview of The Liver 101: Top Conditions, Specialty Testing, and Integrative Medicine Treatment Options. Rupa Health.

Sweetnich, J. (2023f, June 8). Integrative Treatment Options for The Most Common Pulmonary Disorders: Specialty Testing, Nutrition, Supplements. Rupa Health.

Sweetnich, J. (2023g, June 30). Top 5 Antioxidants That Can Improve Your Health and How To Test Your Patient’s Levels. Rupa Health.

Teeter, L. A. (2023, April 25). Complementary and Integrative Medicine for The Treatment of Autoimmune Diseases. Rupa Health.

University of Rochester Medical Center. (2024). Sex Hormone Binding Globulin (Blood) - Health Encyclopedia - University of Rochester Medical Center (A. Finke, C. Haldeman-Englert, & T. Novick, Eds.).

Wang, H., Zhang, H., Gao, Z., Zhang, Q., & Gu, C. (2022). The mechanism of berberine alleviating metabolic disorder based on gut microbiome. Frontiers in Cellular and Infection Microbiology, 12.

Wang, H., Zhu, C., Ying, Y., Luo, L., Huang, D., & Luo, Z. (2017). Metformin and berberine, two versatile drugs in treatment of common metabolic diseases. Oncotarget, 9(11), 10135–10146.

Wang, L., Liu, D., Wei, G., & Ge, H. (2021). Berberine and Metformin in the Treatment of Type 2 Diabetes Mellitus: A Systemic Review and Meta-Analysis of Randomized Clinical Trials. Health, 13(11), 1314–1329.

Wei, W., Zhao, H., Wang, A., Sui, M., Liang, K., Deng, H., Ma, Y., Zhang, Y., Zhang, H., & Guan, Y. (2012). A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndrome. European Journal of Endocrinology, 166(1), 99–105.

Weinberg, J. (2022, December 19). How Short Chain Fatty Acids Affects Our Mood, Digestion, and Metabolism. Rupa Health.

Weinberg, J. L. (2023, February 21). 5 Lab Test To Run on Your Hypoglycemia Patients. Rupa Health.

Weinberg, J. L. (2024, February 2). A Functional Medicine Approach to Jaundice. Rupa Health.

Wu, H., Huang, D., Zhou, H., Sima, X., Wu, Z., Sun, Y., Wang, L., Ruan, Y., Wu, Q., Wu, F., She, T., Chu, Y., Huang, Q., Ning, Z., & Zhang, H. (2022). Metformin: A promising drug for human cancers (Review). Oncology Letters, 24(1).

Xie, L., Zhang, D., Ma, H., He, H., Xia, Q., Shen, W., Chang, H., Deng, Y., Wu, Q., Cong, J., Wang, C. C., & Wu, X. (2019). The Effect of Berberine on Reproduction and Metabolism in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Control Trials. Evidence-Based Complementary and Alternative Medicine, 2019, 1–14.

Xie, W., Su, F., Wang, G., Peng, Z., Xu, Y., Zhang, Y., Xu, N., Hou, K., Hu, Z., Chen, Y., & Chen, R. (2022). Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Frontiers in Pharmacology, 13, 1015045.

Xiong, R.-G., Huang, S.-Y., Wu, S.-X., Zhou, D.-D., Yang, Z.-J., Saimaiti, A., Zhao, C.-N., Shang, A., Zhang, Y.-J., Gan, R.-Y., & Li, H.-B. (2022). Anticancer Effects and Mechanisms of Berberine from Medicinal Herbs: An Update Review. Molecules (Basel, Switzerland), 27(14), 4523.

Yang, J., Yin, J., Gao, H., Xu, L., Wang, Y., Xu, L., & Li, M. (2012). Berberine Improves Insulin Sensitivity by Inhibiting Fat Store and Adjusting Adipokines Profile in Human Preadipocytes and Metabolic Syndrome Patients. Evidence-Based Complementary and Alternative Medicine : ECAM, 2012.

Yin, J., Xing, H., & Ye, J. (2008). Efficacy of Berberine in Patients with Type 2 Diabetes Mellitus. Metabolism, 57(5), 712–717.

Subscribe to the Magazine for free to keep reading!
Subscribe for free to keep reading, If you are already subscribed, enter your email address to log back in.
Thanks for subscribing!
Oops! Something went wrong while submitting the form.
Are you a healthcare practitioner?
Thanks for subscribing!
Oops! Something went wrong while submitting the form.