Berberine and insulin resistance in non-diabetic adults: An updated systematic review and meta-analysis of randomized controlled trials

Abstract

Berberine is a plant alkaloid with insulin-sensitizing properties. Recent meta-analyses have addressed glycemic endpoints and components of the metabolic syndrome, but none has specifically synthesized its effect on insulin resistance measured by the homeostatic model assessment of insulin resistance in non-diabetic populations. The objective was to estimate that effect in non-diabetic adults. We searched PubMed for randomized controlled trials comparing berberine, in any salt, formulation or dose, alone or as an add-on, with a non-berberine control or an active comparator, in non-diabetic adults with insulin resistance or metabolic risk. The primary outcome was the mean difference in the homeostatic model assessment of insulin resistance. A random-effects model was fitted by restricted maximum likelihood, with subgroup and leave-one-out sensitivity analyses and risk-of-bias appraisal using the RoB 2 tool. Of 56 records, nine trials met eligibility and six, comprising 485 participants, provided extractable data. Berberine reduced insulin resistance versus control by a mean difference of −0.95 (95% confidence interval −1.29 to −0.61), with substantial heterogeneity. The effect was larger and homogeneous in polycystic ovary syndrome and smaller in the metabolic and prediabetic subgroup. The prediction interval crossed the null. Five of six pooled trials carried some concerns and the single low-risk trial, which was the largest, showed no effect. In conclusion, berberine was associated with a reduction in insulin resistance, most consistently in polycystic ovary syndrome, but the pooled effect was driven by smaller trials at higher risk of bias. Larger and methodologically rigorous trials are needed before any clinical recommendation.