Effects of red clover (Trifolium pratense L.) on type 2 diabetes mellitus parameters: a systematic review

Abstract

Background: Red clover (Trifolium pratense) and its isoflavones (formononetin, biochanin A) have been investigated for their potential effects on glucose metabolism and related metabolic outcomes. Methods: A comprehensive systematic search was conducted according to PRISMA guidelines by searching PubMed, Web of Science, Embase, Scopus, and Google scholar for studies evaluating the effects of red clover extracts or isolated isoflavones on glycemic outcomes. Human, animal, and in vitro studies were included. Results: Sixteen studies (18 datasets) met eligibility criteria, including 3 human studies, 11 animal studies, and 4 in-vitro studies. The in vitro studies consistently demonstrated favorable effects of red clover on glucose metabolism, including enhanced β-cell viability, reduced apoptosis, increased insulin secretion, and activation of metabolic pathways such as PPAR-α. Animal studies generally reported improvements in glycemic control and insulin sensitivity, including reductions in fasting glucose and HbA1c and modulation of metabolic regulators such as SIRT1. In contrast, evidence from human trials was limited and inconsistent. Only one randomized controlled trial reported a significant improvement in fasting insulin, whereas no consistent effects were observed for fasting glucose or HbA1c across studies. Interpretation of the clinical evidence is limited by the small number of trials, small sample sizes, and heterogeneity in study populations, interventions, and outcome measures. Conclusion: Preclinical findings suggest that red clover may exert glucose-lowering and insulin-sensitizing effects; however, these findings have not been consistently confirmed in human studies. High-quality, adequately powered randomized controlled trials using standardized red clover preparations are required to establish its efficacy and safety in metabolic disease management. © The Author(s) 2026.