Pharmacokinetic and Pharmacodynamics Interactions between Andrographis paniculata, Andrographolide, and Oral Antidiabetic Drugs: A Systematic Review of Preclinical Evidence

Herb–drug interactions between Andrographis paniculata, its constituent andrographolide, and oral antidiabetic drugs may alter drug exposure and glycemic responses. In this systematic review, we assessed the pharmacokinetic and pharmacodynamics interactions between A. paniculata or andrographolide and oral antidiabetic drugs. We searched PubMed, Scopus, ScienceDirect, SpringerLink, Web of Science, EBSCOhost, Portal Garuda, and other databases for articles published through August 2025. Search terms included free-text and Medical Subject Headings (MeSH) keywords: “Herb–Drug Interactions,” andrographolide, Andrographis paniculata, and oral antidiabetic drugs (MeSH: Hypoglycemic Agents). Sixty-one records were identified; 10 preclinical reports were included, and no eligible human clinical studies were found. Heterogeneity in preparation type, dosing, and study design precluded meta-analysis; therefore, a narrative synthesis was performed. Across the included studies, combinations of A. paniculata or andrographolide with sulfonylureas often significantly increased drug exposure (maximum plasma concentration [Cmax]; area under the concentration–time curve [AUC]) and enhanced glucose-lowering. Repeated andrographolide dosing significantly reduced glipizide exposure and attenuated its effects. Tolbutamide exhibited pharmacokinetic–pharmacodynamics dissociation, with significantly reduced exposure but preserved hypoglycemic activity. Saxagliptin exposure increased with reduced clearance; repaglinide showed higher Cmax and AUC with augmented glucose-lowering effects; metformin exhibited increased exposure with enhanced glycemic control; and acarbose showed no meaningful change. Overall, the findings suggest that A. paniculata and andrographolide potentiate the pharmacokinetic/pharmacodynamics effects of some oral antidiabetic drugs, whereas acarbose shows no interaction. Glipizide exhibits either synergistic or antagonistic effects depending on the preparation type. These context-dependent findings highlight the need for preparation-specific evaluation and clinical verification.