To systematically evaluate the efficacy and safety of berberine alone or combined with oral hypoglycemic agents in type 2 diabetes mellitus (T2DM), and explore whether baseline glycemic status affects treatment effect consistency.

We systematically searched PubMed, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP databases from inception to January 1, 2026. We included T2DM clinical studies using berberine alone or combined with standard glucose-lowering therapies. Outcomes included fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), 2-hour postprandial blood glucose (2hPBG), and safety (adverse events, hypoglycemia). Subgroup analyses were performed by baseline FPG/HbA1c; publication bias was assessed via funnel plots and Egger’s test.

Thirty-three studies (3,131 participants) were included, with intervention durations of 14 days to 6 months and berberine doses of 0.9-2.4 g/day. Compared with controls, berberine significantly reduced FPG (WMD=-0.78 mmol/L), HbA1c (WMD=-0.63%), and 2hPBG (MD=-1.11 mmol/L). Subgroup effects were directionally consistent; HbA1c reduction was greater in patients with baseline HbA1c≥9.0% (-0.79% vs -0.58%). Berberine was associated with lower risks of total adverse events (RR=0.73) and hypoglycemia (RR=0.59). No significant publication bias was detected.

Berberine as adjunctive therapy improves glycemic control in T2DM without increasing safety risk, and may reduce adverse events and hypoglycemia. Baseline glycemic status may affect effect magnitude. Further high-quality randomized controlled trials are needed to confirm optimal populations and clinical applications.