Currently submitted to: Journal of Medical Internet Research
Date Submitted: Sep 10, 2026
Open Peer Review Period: Sep 11, 2026 - Nov 6, 2026
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Berberine for Type 2 Diabetes: A Bayesian Network Meta-Analysis of Dose-Specific Comparisons With First-Line Antidiabetic Agents
ABSTRACT
Background:
Background:
Berberine is widely used off-label for type 2 diabetes mellitus (T2DM) without regulatory approval or guideline endorsement, and dose-specific comparisons with first-line antidiabetic drugs are lacking.
Objective:
Objective:
This study aimed to compare berberine doses with placebo and standard antidiabetic agents across glycemic, metabolic, and safety outcomes.
Methods:
Methods:
We searched PubMed, Embase, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov from inception to January 1, 2026, for randomized controlled trials (RCTs) comparing oral berberine monotherapy with placebo or any active antidiabetic drug in adults with T2DM, and performed a random-effects Bayesian network meta-analysis with SUCRA ranking and CINeMA certainty assessment.
Results:
Results:
We included 16 RCTs with 1460 participants. Berberine 1500 mg/day produced the greatest HbA1c reduction versus placebo (mean difference −1.13%, 95% CrI −1.98 to −0.52; SUCRA 97.9%) and significantly lowered HbA1c versus metformin 1500 mg/day (−1.07%, −1.66 to −0.49) and rosiglitazone 4 mg/day (−1.12%, −2.15 to −0.08). Berberine 2000 mg/day gave the largest fasting glucose reduction versus placebo (−1.93 mmol/L, −3.59 to −0.29). Effects on lipids and body mass index were small, generally nonsignificant, and below minimal clinically important differences. Gastrointestinal events increased at higher doses, but sparse data precluded precise estimates.
Conclusions:
Conclusion: Berberine 1500 mg/day showed superior glycemic control versus placebo, metformin, and rosiglitazone, whereas metabolic benefits were modest and higher doses raised tolerability concerns. Confirmatory trials are needed before guideline recommendations can be made. Clinical Trial: The protocol for this systematic review and network meta-analysis was registered prospectively with PROSPERO (CRD420251088450). We conducted the review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for meta-analyses (Appendix 1)
Citation
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