Treatment of Type 2 Diabetes and Dyslipidemia with the Natural Plant Alkaloid Berberine
Abstract
Context: Berberine, a natural plant alkaloid, is usually used as an antibiotic drug. The potential glucose-lowering effect of berberine was noted when it was used for diarrhea in diabetic patients. In vitro and in vivo studies have then showed its effects on hyperglycemia and dyslipidemia. Objective: The objective of the study was to evaluate the efficacy and safety of berberine in the treatment of type 2 diabetic patients with dyslipidemia. Design: One hundred sixteen patients with type 2 diabetes and dyslipidemia were randomly allocated to receive berberine (1.0 g daily) and the placebo for 3 months. The primary outcomes were changes in plasma glucose and serum lipid concentrations. Glucose disposal rate (GDR) was measured using a hyperinsulinemic euglycemic clamp to assess insulin sensitivity. Results: In the berberine group, fasting and postload plasma glucose decreased from 7.0 ± 0.8 to 5.6 ± 0.9 and from 12.0 ± 2.7 to 8.9 ± 2.8 mm/liter, HbA1c from 7.5 ± 1.0% to 6.6 ± 0.7%, triglyceride from 2.51 ± 2.04 to 1.61 ± 1.10 mm/liter, total cholesterol from 5.31 ± 0.98 to 4.35 ± 0.96 mm/liter, and low-density lipoprotein-cholesterol from 3.23 ± 0.81 to 2.55 ± 0.77 mm/liter, with all parameters differing from placebo significantly (P < 0.0001, P < 0.0001, P < 0.0001, P = 0.001, P < 0.0001, and P <0.0001, respectively). The glucose disposal rate was increased after berberine treatment (P = 0.037), although no significant change was found between berberine and placebo groups (P = 0.063). Mild to moderate constipation was observed in five participants in the berberine group. Conclusions: Berberine is effective and safe in the treatment of type 2 diabetes and dyslipidemia.
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Two cases of liver function abnormalities were reported in one study in the berberine group, while two studies reported no increase or a decrease in liver transaminases with berberine.
“Two cases of liver function abnormalities were reported in one study in the berberine group,(29) although two studies reported no increase or a decrease in liver transaminases with berberine.(32, 34)”
From Overall and sex-specific effect of berberine for dyslipidemia: systematic review and meta-analysis of placebo-controlled trials (2022) · cites this paper as [32]
The lack of FPG effect in the 90-day subgroup was likely due to most participants in this subgroup having normal blood glucose levels, as berberine does not significantly affect normal values for these indicators.
“Further analysis suggested that this was likely due to most participants in this subgroup having normal blood glucose levels, as berberine does not significantly affect normal values for these indicators (Zhang et al., 2008; An et al., 2014; Wang et al., 2016b).”
From Efficacy and safety of berberine on the components of metabolic syndrome: a systematic review and meta-analysis of randomized placebo-controlled trials (2025) · cites this paper as Zhang et al., 2008
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“In addition, a randomized, double-blind, placebo-controlled and multiple-center trial [3] showed that treatment with berberine (0.”
BackgroundLiu, Z., Liu, Q., Xu, B., Wu, J., Guo, C. H., Zhu, F., Yang, Q., Gao, G., Gong, Y., & Shao, C. (2009) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2008.12.009 · Cited by 140 · see citing works
Lipid-lowering effect of berberine in human subjects and rats
Hu, Y., Ehli, E. A., Kittelsrud, J. M., Ronan, P. J., Munger, K. A., Downey, T., Bohlen, K., Callahan, L. B., Munson, V., Jahnke, M., et al. (2012) · Phytomedicine · doi:10.1016/j.phymed.2012.05.009 · Cited by 136 · see citing works
“) when compared to other berberine trials (Kong et al. 2008; Yin et al. 2008; Zhang et al. 2008).”
BackgroundResultInfluentialBerberine Modulates Gut Microbiota and Reduces Insulin Resistance via the TLR4 Signaling Pathway
Liu, D., Zhang, Y., Liu, Y., Hou, L.-Q., Li, S., Tian, H., & Zhao, T.-Y. (2018) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0043-125066 · Cited by 136 · see citing works
“Low-dose berberine has also been proven to have beneficial effects for T2DM and dyslipidemia with few side effects [13, 14].”
Self-citationAnti-Diabetic Agents from Natural Products — An Update from 2004 to 2009
Qi, L., Liu, E., Chu, C., Peng, Y., Cai, H., & Li, P. (2010) · Current Topics in Medicinal Chemistry · doi:10.2174/156802610790980620 · Cited by 135 · see citing works
“Li’s group performed a randomized, double-blind, placebo controlled trial in four centers to evaluate the efficacy and safety of berberine in the treatment of DM and dyslipidemia, demonstrating that berberine is effective and safe in the treatment of type 2 DM and dyslipidemia [43].”
MethodBerberine promotes the recruitment and activation of brown adipose tissue in mice and humans
Wu, L., Xia, M., Duan, Y., Zhang, L., Jiang, H., Hu, X., Yan, H., Zhang, Y., Gu, Y., Shi, H., et al. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1706-y · Cited by 135 · see citing works
Self-citationAffuso, F., Ruvolo, A., Micillo, F., Saccà, L., & Fazio, S. (2009) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2009.05.017 · Cited by 135 · see citing works
“In addition, berberine, a natural plant alkaloid, is not only effective in lowering lipids and in the treatment of type 2 diabetes [13], but it also upregulates the number and function of circulating endothelial progenitor cells (EPCs), leading to increased nitric oxide production and endothelial function [14].”
BackgroundInfluentialAnsari, N., & Khodagholi, F. (2013) · Current Neuropharmacology · doi:10.2174/1570159x11311040005 · Cited by 131 · see citing works
“Gastrointestinal symptoms such as diarrhea, constipation, flatulence and abdominal pain were the main reported side effects of BBR treatment in human subjects [191, 192].”
BackgroundHarrison, S. A., Gunn, N., Neff, G. W., Kohli, A., Liu, L., Flyer, A., Goldkind, L., & Bisceglie, A. M. D. (2021) · Nature Communications · doi:10.1038/s41467-021-25701-5 · Cited by 131 · see citing works
Liang, Y., Xu, X., Yin, M., Zhang, Y., Huang, L., Chen, R., & Ni, J. (2018) · Endocrine Journal · doi:10.1507/endocrj.ej18-0109 · Cited by 130 · see citing works
“2008 [15] Randomized, double-blind, placebocontrolled and multiple-center trial 58/52 Newly diagnosed 51 ± 9/51 ± 10 Berberine/ placebo 0.”
BackgroundMethodSelf-citationJu, J., Li, J., Lin, Q., & Xu, H. (2018) · Phytomedicine · doi:10.1016/j.phymed.2018.09.212 · Cited by 124 · see citing works
Modulating the Microbiota as a Therapeutic Intervention for Type 2 Diabetes
Huda, M. N., Kim, M., & Bennett, B. J. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.632335 · Cited by 129 · see citing works
Berberine is an insulin secretagogue targeting the KCNH6 potassium channel
Zhao, M., Lü, J., Li, S., Wang, H., Cao, X., Li, Q., Shi, T., Matsunaga, K., Chen, C., Huang, H., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25952-2 · Cited by 123 · see citing works
Self-citationBerberine as a promising anti-diabetic nephropathy drug: An analysis of its effects and mechanisms
Ni, W., Ding, H., & Tang, L. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.04.017 · Cited by 120 · see citing works
“In addition to evidence from animal models and cultured cells, the anti-inflammatory effect of berberine has also been identified in clinical studies (Zhang et al., 2008).”
BackgroundQin, X., Guo, B.-S., Wan, B., Fang, L., Lü, L., Wu, L., Zang, Y. Q., & Zhang, J. Z. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903853 · Cited by 122 · see citing works
“The finding related to the IL-6–reducing effect of BBR is consistent with other reports that BBR treatment results in decreased expression of IL-6 in macrophages (44) and that reduced serum IL-6 levels were found in individuals treated with BBR in controlled clinical trials (36).”
BackgroundResultAntidiabetic claims of Tinospora cordifolia (Willd.) Miers: critical appraisal and role in therapy
Sharma, R., Amin, H., Galib, & Prajapati, P. (2015) · Asian Pacific Journal of Tropical Biomedicine · doi:10.1016/s2221-1691(15)30173-8 · Cited by 118 · see citing works
“Hypoglycaemic Decreases the blood glucose level and increases glucose tolerance [15]”
BackgroundEffect of berberine administration on metabolic syndrome, insulin sensitivity, and insulin secretion
Pérez-Rubio, K. G., González-Ortiz, M., Martínez-Abundis, E., Robles-Cervantes, J. A., & Espinel-Bermúdez, M. C. (2013) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2012.0183 · Cited by 113 · see citing works
“This was certainly due to an increment in insulin sensitivity and decrease in insulin secretion.(14,15) Similar findings regarding metabolic control have recently been published with the administration of berberine alone or in combination with other nutraceutical compounds.”
Gao, K., Yang, R., Zhang, J., Wang, Z., Jia, C., Zhang, F., Li, S., Wang, J., Murtaza, G., Xie, H., et al. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.01.011 · Cited by 117 · see citing works
Tian, J., Jin, D., Bao, Q. D., Ding, Q., Zhang, H., Gao, Z., Song, J., Lian, F., & Tong, X. (2019) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13760 · Cited by 117 · see citing works
“05).(19) One RCT revealed that Tangke soft capsules reduced the levels of HbAlc, FPG and 2hPG compared with baseline levels (P < .”
BackgroundXu, Y., Yu, T., Ma, G., Zheng, L., Jiang, X., Yang, F., Wang, Z., Li, N., He, Z., Song, X., et al. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.62556 · Cited by 110 · see citing works
“It has received increasing attention for a variety of metabolic benefits in recent years[24, 25].”
BackgroundTabeshpour, J., Imenshahidi, M., & Hosseinzadeh, H. (2017) · Europe PMC (PubMed Central) · doi:10.22038/ijbms.2017.8682 · Cited by 115 · see citing works
Li, M., Shu, X., Xu, H., Zhang, C., Yang, L., Zhang, L. R., & Ji, G. (2016) · Journal of Translational Medicine · doi:10.1186/s12967-016-0987-5 · Cited by 114 · see citing works
“anti-microbial medicine, possesses an anti-hyperlipidemic potential [7, 8].”
Belwal, T., Bisht, A., Devkota, H. P., Ullah, H., Khan, H. Z., Pandey, A., BHATT, I. D., & Echeverría, J. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00041 · Cited by 115 · see citing works
Guo, J., Chen, H., Zhang, X., Lou, W., Zhang, P., Qiu, Y., Zhang, C., Wang, Y., & Liu, W. J. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/2074610 · Cited by 110 · see citing works
Self-citationTeodoro, J. S., Duarte, F. V., Gomes, A. P., Varela, A. T. I. F., Peixoto, F., Rolo, A. P., & Palmeira, C. M. (2013) · Mitochondrion · doi:10.1016/j.mito.2013.09.002 · Cited by 111 · see citing works
“, 2011), but also increasing insulin expression, β-cell regeneration, antioxidant enzyme activity, glucose uptake, while decreasing lipid peroxidation (Wang et al., 2009a; Zhang et al., 2008; Zhou et al., 2009) and cholesterol and triglyceride synthesis (Brusq et al.”
BackgroundYe, Y., Liu, X., Wu, N., Han, Y., Wang, J., Yu, Y., & Chen, Q. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.653887 · Cited by 109 · see citing works
Marazzi, G., Cacciotti, L., Pelliccia, F., Iaia, L., Volterrani, M., Caminiti, G., Sposato, B., Massaro, R., Grieco, F., & Rosano, G. (2011) · Advances in Therapy · doi:10.1007/s12325-011-0082-5 · Cited by 107 · see citing works
Zhang, W., Yan-cheng, X. U., Fang-jian, G. U. O., Ye, M., & Li, M. (2008) · Chinese Medical Journal · doi:10.1097/00029330-200811010-00003 · Cited by 107 · see citing works
Protective effect of berberine against LPS-induced injury in the intestine: a review
Izadparast, F., Riahi‐Zanjani, B., Yarmohammadi, F., Hayes, A. W., & Karimi, G. (2022) · Cell Cycle · doi:10.1080/15384101.2022.2100682 · Cited by 109 · see citing works
“Berberine has a diverse range of pharmacological actions, including anticancer [21–23], antidiabetic [24–26], antiobesity, anti-hyperlipidemic [25,27], cardio protective [25,28], and spatial memory improvement [25,29], immunosuppressive [30] properties, as well as antioxidant and anti-inflam matory activity [31,32].”
BackgroundBioactivities of berberine metabolites after transformation through CYP450 isoenzymes
Li, Y., Ren, G., Wang, Y.-X., Kong, W.-J., Yang, P., Wang, Y.-M., Li, Y.-H., Yi, H., Li, Z.-R., Song, D.-Q., et al. (2011) · Journal of Translational Medicine · doi:10.1186/1479-5876-9-62 · Cited by 109 · see citing works
“Clinical studies showed that oral administration of BBR caused significant reduction of blood cholesterol, triglyceride as well as glucose in patients with hyperlipidemia and type 2 diabetes [2,3,5-7], with no side-effects on liver, kidney and muscle [2,5].”
BackgroundSelf-citationWang, S., Ren, H., Zhong, H., Zhao, X., Li, C., Ma, J., Gu, X., Xue, Y., Huang, S., Yang, J., et al. (2021) · Gut Microbes · doi:10.1080/19490976.2021.2003176 · Cited by 108 · see citing works
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Berberine inhibits PTP1B activity and mimics insulin action
Chen, C., Zhang, Y., & Huang, C. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.05.153 · Cited by 106 · see citing works
Self-citationIqbal, M. J., Quispe, C., Javed, Z., Sadia, H., Qadri, Q. R., Raza, S., Salehi, B., Martins, N. A., Mohamed, Z. A., Mohammed, J. S., et al. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.624494 · Cited by 106 · see citing works
“Pharmacokinetic profile of berberine has been reported in plenty of studies that it has low rate of absorption, especially when taken orally (Zhang et al., 2008; Alolga et al., 2016).”
BackgroundSarna, L. K., Wu, N., Hwang, S., Siow, Y. L., & Karmin, O. (2010) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y09-136 · Cited by 107 · see citing works
Berberine Inhibits Inflammatory Response and Ameliorates Insulin Resistance in Hepatocytes
Lou, T., Zhang, Z., Xi, Z., Liu, K., Li, L., Liu, B., & Huang, F. (2010) · Inflammation · doi:10.1007/s10753-010-9276-2 · Cited by 104 · see citing works
“modulation in sugar and lipid metabolic disorders [14].”
BackgroundProtective Effects of Berberine on Doxorubicin-Induced Hepatotoxicity in Mice
Zhao, X., Zhang, J., Tong, N., Chen, Y., & Luo, Y. (2012) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.35.796 · Cited by 105 · see citing works
Berberine as a Promising Safe Anti-Cancer Agent- Is there a Role for Mitochondria?
Diogo, C. V., Machado, N. G., Barbosa, I. A., Serafim, T. L., Burgeiro, A., & Oliveira, P. J. (2011) · Current Drug Targets · doi:10.2174/138945011795528930 · Cited by 104 · see citing works
“[108] Zhang Y, Li X, Zou D, Liu W, Yang J, Zhu N, et al.”
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Self-citationBerberine and Its Study as an Antidiabetic Compound
Utami, A. R., Maksum, I. P., & Deawati, Y. (2023) · Biology · doi:10.3390/biology12070973 · Cited by 110 · see citing works
- Authors
- Zhang, Y., Li, X., Zou, D., Liu, W., Yang, J., Zhu, N., Huo, L., Wang, M., Hong, J., Wu, P., Ren, G., & Ning, G.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Second Military Medical University (CN)
- Department of Endocrinology (J.Y., G.R.), Min-Hang Hospital, Shanghai 201100, People’s Republic of China
- Corresponding author
- Ning, Guang
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2008-07-01
- Volume
- 93
- Issue
- 7
- Pages
- 2559-2565
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1969395627
- Cited by
- 573
- References
- 23
- Citations by year
- 2026: 30 · 2025: 27 · 2024: 28 · 2023: 33 · 2022: 41 · 2021: 54 · 2020: 46 · 2019: 42 · 2018: 33 · 2017: 23 · 2016: 29 · 2015: 32 · 2014: 34 · 2013: 31 · 2012: 25
- FWCI
- 14.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- berberine, type 2 diabetes, dyslipidemia, glucose-lowering effect, insulin sensitivity, glucose disposal rate, hyperinsulinemic-euglycemic clamp, HbA1c, serum lipids, triglycerides, LDL cholesterol, total cholesterol, plant alkaloids, constipation, drug safety, antidiabetic therapy, lipid-lowering therapy
- MeSH terms
- Adult, Aged, Berberine, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Glycated Hemoglobin, Humans, Insulin, Insulin Resistance, Cholesterol, LDL, Male, Middle Aged, Triglycerides, Dyslipidemias
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