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ORCID ID

Dinda Ayu Permatasari: https://orcid.org/0009-0001-8331-371X

Abdul Khairul Rizki Purba: https://orcid.org/0000-0002-9372-2656

Maftuchah Rochmanti: https://orcid.org/0000-0002-9222-9376

Rizky Alvian Adi Kurniawan: https://orcid.org/0009-0004-8444-3331

Shilvi Haliza Pratiwi: https://orcid.org/0009-0008-9651-8096

Abstract

Metformin is widely recognized as an effective glucose-lowering agent for type 2 diabetes mellitus, while epigallocatechin gallate (EGCG) has exhibited promising antidiabetic and antioxidant properties in experimental settings. This systematic review and meta-analysis aimed to assess the impact of EGCG and metformin on blood glucose concentrations in diabetic zebrafish models and to synthesize the related metabolic and mechanistic findings. The protocol was registered with PROSPERO (CRD420261461237) and the review was conducted in accordance with PRISMA 2020 guidelines. Comprehensive searches were performed in PubMed/MEDLINE, Scopus, Web of Science, and Embase for in vivo zebrafish studies published from January 2010 to August 2025. Inclusion criteria encompassed studies investigating EGCG or metformin in experimentally induced diabetic zebrafish that reported measurable glucose-related outcomes. Blood glucose effects were quantified as mean differences (MDs) with 95% confidence intervals (CIs). Data from metformin studies were synthesized using a random-effects inverse-variance model, whereas the solitary EGCG study was reported as an individual quantitative estimate. Risk of bias was evaluated utilizing SYRCLE's risk-of-bias tool. Three studies fulfilled the inclusion criteria: two assessed metformin and one evaluated EGCG. Metformin administration resulted in a statistically significant reduction in blood glucose relative to untreated diabetic controls (pooled MD –42.45 mg/dL; 95% CI –65.09 to –19.82; p = 0.0002), accompanied by moderate-to-substantial heterogeneity (I2 = 66%). Nevertheless, the pooled estimate was heavily influenced by one study employing graph-extracted outcome data. The single EGCG study demonstrated a pronounced glucose-lowering effect (MD –202.00 mg/dL; 95% CI –214.48 to –189.52; p < 0.00001), precluding pooled analysis or heterogeneity assessment. Secondary outcomes indicated potential influences on tissue regeneration, glucose tolerance, lipid metabolism, metabolic gene expression, and gut microbiota composition, although mechanistic insights remained sparse. Several risk-of-bias domains were rated as unclear due to incomplete reporting of randomization, allocation concealment, and blinding procedures. In conclusion, metformin exhibited a significant pooled glucose-lowering effect in diabetic zebrafish; however, the limited number of studies, considerable methodological variability, and sensitivity to graph-estimated data diminished the strength of the evidence. EGCG showed a substantial individual effect, yet independent replication is necessary to confirm its efficacy. Future investigations should adopt standardized diabetes induction protocols, species-validated dosing regimens, comprehensive numerical outcome reporting, and factorial designs to evaluate metformin, EGCG, and their combined effects.

Keywords

Epigallocatechin gallate (EGCG), Metformin, Zebrafish, Diabetes Mellitus, Blood glucose

First Page

180

Last Page

195

DOI

10.65346/2599-056X.2442

Publication Date

6-30-2026

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