Natural Products Targeting GLP-1: Insights into Herbal Therapy for Insulin Resistance and Beta-Cell Function

The rising global prevalence of Type 2 Diabetes Mellitus (T2DM) and obesity has intensified the search for novel therapeutic agents, with Glucagon-like peptide-1 (GLP-1) emerging as a key regulator of glucose homeostasis and insulin secretion. While synthetic GLP-1 receptor agonists (RAs) like semaglutide and tirzepatide dominate clinical use, plant-derived GLP-1 modulators present a promising alternative due to their natural origin, diverse mechanisms, and potential for reduced side effects. This review systematically evaluates 34 medicinal plants—including Agave tequilana (fructans), Berberis vulgaris (berberine), Momordica charantia (bitter melon), and Panax ginseng (ginsenosides)—that exhibit GLP-1 agonist activity through pathways such as DPP-4 inhibition, bitter taste receptor activation, and SCFA-mediated GLP-1 secretion. Comparative analysis reveals that while synthetic agonists offer superior HbA1c reduction (1–2%) and weight loss (5–22.5%), natural compounds provide multimodal benefits, including anti-inflammatory, antioxidant, and beta-cell protective effects. However, clinical evidence remains limited, with most studies confined to preclinical models. Future research should prioritize human trials, bioavailability optimization, and synergistic formulations to harness the full therapeutic potential of plant-derived GLP-1 agonists in metabolic disorders.