The Effect of Resveratrol on Fasting Blood Glucose Levels as a Parameter of Type 2 Diabetes Mellitus
Abstract
characterized by chronic hyperglycemia, insulin resistance, and increased oxidative stress. Resveratrol, a naturally occurring polyphenolic compound, has been widely investigated for its potential antidiabetic effects in preclinical studies, although findings across animal models remain inconsistent and require systematic synthesis. This study aimed to review and synthesize evidence on the effects of resveratrol on glycemic regulation, insulin signaling, lipid metabolism, and oxidative stress in animal models of T2DM. The review followed PRISMA 2020 guidelines. Electronic searches were conducted in PubMed, Scopus, Sinta, and Google Scholar for articles published between 2019 and 2024. Eligible studies were original experimental investigations employing animal models of T2DM with resveratrol as the primary intervention. Owing to heterogeneity in study designs and outcome measures, data were synthesized using a qualitative narrative approach. Seven studies met the inclusion criteria. Overall, resveratrol administration was associated with reductions in fasting blood glucose, improvements in insulin sensitivity, and modulation of key insulin signaling pathways, particularly the PI3K Akt FOXO1 axis. Most studies also reported favorable effects on lipid profiles and reductions in oxidative stress markers. Although one study reported no significant improvement in glycemic indices, the overall pattern indicated consistent positive metabolic effects. This systematic review suggests that resveratrol exerts antidiabetic effects in animal models of T2DM by improving glycemic control, insulin signaling, lipid metabolism, and oxidative stress regulation. However, further well designed studies are needed to clarify dose response relationships and facilitate clinical translation.
References
Adelita, M., Arto, K. S., & Deliana, M. (2020). Kontrol Metabolik pada Diabetes Melitus Tipe-1. Cermin Dunia Kedokteran, 47(3), 227–232. https://doi.org/10.55175/CDK.V47I3.360
Alanazi, A. Z., Alqinyah, M., Alhamed, A. S., Mohammed, H., Raish, M., Aljerian, K., Alsabhan, J. F., & Alhazzani, K. (2024). Cardioprotective Effects of Liposomal Resveratrol in Diabetic Rats: Unveiling Antioxidant and Anti-Inflammatory Benefits. Redox Report, 29(1). https://doi.org/10.1080/13510002.2024.2416835
Andrejic, N., Božovic, I., Moradi, H., Tataei, R., & Knezevic, N. N. (2025). Neuropathic pain management: A focused review of current treatments and novel data from main ongoing clinical trials. Expert opinion on investigational drugs, 34(4), 287-299. https://doi.org/10.1080/13543784.2025.2473692
Bakri, A. H., Bamahry, A., Pratama, A. A., Haidir Bima, I., & Yanti, A. K. E. (2023). Relationship between Age, Gender and Body Mass Index (BMI) with HbA1c Levels at Ibnu Sina Hospital Makassar. Fakumi Medical Journal: Jurnal Mahasiswa Kedokteran, 3(9), 677–684. https://doi.org/10.33096/fmj.v3i9.297
Bejenaru, L. E., Biţă, A., Belu, I., Segneanu, A. E., Radu, A., Dumitru, A., ... & Bejenaru, C. (2024). Resveratrol: A review on the biological activity and applications. Applied Sciences, 14(11), 4534. https://doi.org/10.3390/app14114534
Das, S., Behera, J. P., Rojaramani, Y., & Mohanty, R. R. (2019). Effects of Resveratrol on Oxidative Stress in High Fat Diet /Streptozocin Induced Diabetic Wistar Albino Rats. International Journal of Basic & Clinical Pharmacology, 8(3), 482. https://doi.org/10.18203/2319-2003.ijbcp20190651
Dwivedi, S., & Sikarwar, M. S. (2025). Diabetic nephropathy: pathogenesis, mechanisms, and therapeutic strategies. Hormone and Metabolic Research, 57(01), 7-17. https://doi.org/10.1055/a-2435-8264
Guan, H., Tian, J., Wang, Y., Niu, P., Zhang, Y., Zhang, Y., ... & Tong, X. (2024). Advances in secondary prevention mechanisms of macrovascular complications in type 2 diabetes mellitus patients: a comprehensive review. European Journal of Medical Research, 29(1), 152. https://doi.org/10.1186/s40001-024-01739-1
Hawilla, A., Zulkarnain, A. K., & Lukitaningsih, E. (2023). Stabilitas dan Sifat Fisik Sediaan Mikroemulgel Resveratrol Sebagai Tabir Surya dan Antiaging Secara In Vitro. Majalah Farmaseutik.
Hou, C. Y., Chen, Y. W., Hazeena, S. H., Tain, Y. L., Hsieh, C. W., Chen, D. Q., ... & Shih, M. K. (2024). Cardiovascular risk of dietary trimethylamine oxide precursors and the therapeutic potential of resveratrol and its derivatives. FEBS Open Bio, 14(3), 358-379.
Hussein, A. A., Ahmed, N. A., Sakr, H. I., Atia, T., & Ahmed, O. M. (2024). Omentin roles in physiology and pathophysiology: an up-to-date comprehensive review. Archives of Physiology and Biochemistry, 130(6), 800-813. https://doi.org/10.1080/13813455.2023.2283685
Jadon, A. S., Kaushik, M. P., Anitha, K., Bhatt, S., Bhadauriya, P., & Sharma, M. (2024). Types of diabetes mellitus, mechanism of insulin resistance and associated complications. In Biochemical immunology of diabetes and associated complications (pp. 1-18). Academic Press. https://doi.org/10.1016/B978-0-443-13195-0.00001-6
Koca, B. E., Sarıtaş, S., Bechelany, M., & Karav, S. (2025). The Functional Role of Polyphenols Across the Human Lifespan. International Journal of Molecular Sciences, 26(22), 11074. https://doi.org/10.3390/ijms262211074
Kosmas, C. E., Bousvarou, M. D., Kostara, C. E., Papakonstantinou, E. J., Salamou, E., & Guzman, E. (2023). Insulin resistance and cardiovascular disease. Journal of International Medical Research, 51(3), 03000605231164548. https://doi.org/10.1177/03000605231164548
Koushki, M., Farahani, M., Yekta, R. F., Frazizadeh, N., Bahari, P., Parsamanesh, N., ... & Amiri-Dashatan, N. (2024). Potential role of resveratrol in prevention and therapy of diabetic complications: a critical review. Food & nutrition research, 68, 10-29219. https://doi.org/10.29219/fnr.v68.9731
Laily, W. N., Wati, D. A., Suci Ayu, R. N., & Pratiwi, A. R. (2022). Hubungan Tingkat Konsumsi Bahan Makanan Sumber Isoflavon dan Serat Dengan Kadar Hba1c Pasien Diabetes Mellitus Tipe II di Rumah Sakit DR. H. Bob Bazar Lampung Selatan. Jurnal Kedokteran Dan Kesehatan: Publikasi Ilmiah Fakultas Kedokteran Universitas Sriwijaya, 9(2), 153–160. https://doi.org/10.32539/JKK.V9I2.17014
Lestari, Zulkarnain, & Sijid, S. A. (2021). Diabetes Melitus: Review Etiologi, Patofisiologi, Gejala, Penyebab, Cara Pemeriksaan, Cara Pengobatan Dan Cara Pencegahan. Prosiding Biologi Achieving The Sustainable Development Goals With Biodiversity In Confronting Climate Change - Jurnal UIN Alauddin.
Mahjabeen, W., Khan, D. A., & Mirza, S. A. (2022). Role of Resveratrol Supplementation in Regulation of Glucose Hemostasis, Inflammation and Oxidative Stress in Patients with Diabetes Mellitus Type 2: A Randomized, Placebo-Controlled Trial. Complementary Therapies in Medicine, 66, 102819. https://doi.org/10.1016/j.ctim.2022.102819
Meng, X., Zhou, J., Zhao, C.-N., Gan, R.-Y., & Li, H.-B. (2020). Health Benefits and Molecular Mechanisms of Resveratrol: A Narrative Review. Foods, 9(3), 340. https://doi.org/10.3390/foods9030340
Munir, K. M., Chandrasekaran, S., Gao, F., & Quon, M. J. (2013). Mechanisms for food polyphenols to ameliorate insulin resistance and endothelial dysfunction: therapeutic implications for diabetes and its cardiovascular complications. American Journal of Physiology-Endocrinology and Metabolism, 305(6), E679-E686. https://doi.org/10.1152/ajpendo.00377.2013
Oyenihi, O. R., Oyenihi, A. B., Adeyanju, A. A., & Oguntibeju, O. O. (2016). Antidiabetic effects of resveratrol: the way forward in its clinical utility. Journal of diabetes research, 2016(1), 9737483. https://doi.org/10.1155/2016/9737483
Rahman, M. A., Jalouli, M., Bhajan, S. K., Al-Zharani, M., & Harrath, A. H. (2025). The Role of Hypoxia-Inducible Factor-1α (HIF-1α) in the Progression of Ovarian Cancer: Perspectives on Female Infertility. Cells, 14(6), 437. https://doi.org/10.3390/cells14060437
Ren, Z. Q., Zheng, S. Y., Sun, Z., Luo, Y., Wang, Y. T., Yi, P., ... & Xiao, W. F. (2025). Resveratrol: Molecular Mechanisms, Health Benefits, and Potential Adverse Effects. MedComm, 6(6), e70252. https://doi.org/10.1002/mco2.70252
Restrepo Tique, M., Araque, O., & Sanchez-Echeverri, L. A. (2024). Technological advances in the diagnosis of cardiovascular disease: a public health strategy. International Journal of Environmental Research and Public Health, 21(8), 1083. https://doi.org/10.3390/ijerph21081083
Sagita, P., Apriliana, E., Mussabiq, S., & Soleha, T. U. (2021). Pengaruh Pemberian Daun Sirsak (Annona muricata) terhadap Penyakit Diabetes Melitus. Jurnal Medika Hutama, 3(01 Oktober), 1265–1272. https://jurnalmedikahutama.com/index.php/JMH/article/view/262
Sapra, A., & Bhandari, P. (2023). Diabetes. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK551501/
Shaito, A., Posadino, A. M., Younes, N., Hasan, H., Halabi, S., Alhababi, D., Al-Mohannadi, A., Abdel-Rahman, W. M., Eid, A. H., Nasrallah, G. K., & Pintus, G. (2020). Potential Adverse Effects of Resveratrol: A Literature Review. International Journal of Molecular Sciences, 21(6), 2084. https://doi.org/10.3390/ijms21062084
Shu, L., Hou, G., Zhao, H., Huang, W., Song, G., & Ma, H. (2020). Resveratrol Improves High-Fat Diet-Induced Insulin Resistance in Mice by Downregulating the lncRNA NONMMUT008655.2. American Journal of Translational Research, 12(1), 1–18.
Singh, A., & Bodakhe, S. H. (2022). Resveratrol Attenuates Behavioural Impairment Associated with Learning and Memory in Rats with Diabetes Induced by a High‐Fat Diet and Streptozotocin. British Journal of Pharmacology, 179(19), 4673–4691. https://doi.org/10.1111/bph.15895
Soliman, A. Y., Elguindy, N. M., Saleh, A. M., & Balbaa, M. (2025). Biochemical and molecular evaluation of resveratrol and selenium nanoparticles in managing type 2 diabetes and its complications. Scientific Reports, 15(1), 25565. https://doi.org/10.1038/s41598-025-11156-x
Szkudelska, K., Deniziak, M., Sassek, M., Szkudelski, I., Noskowiak, W., & Szkudelski, T. (2021). Resveratrol Affects Insulin Signaling in Type 2 Diabetic Goto-Kakizaki Rats. International Journal of Molecular Sciences, 22(5), 2469. https://doi.org/10.3390/ijms22052469
Tamba, L. M., Taileleu, N., & Undaryati, Y. M. (2024). Health Problems in Female Reproductive Organs. Journal of Global Research in Public Health, 9(2), 94-101. https://doi.org/10.30994/jgrph.v9i2.543
Trofin, A. M., Scripcariu, D. V., Filipiuc, S. I., Neagu, A. N., Filipiuc, L. E., Tamba, B. I., ... & Uritu, C. M. (2025). From Nature to Nanomedicine: Enhancing the Antitumor Efficacy of Rhein, Curcumin, and Resveratrol. Medicina, 61(6), 981. https://doi.org/10.3390/medicina61060981
Tshivhase, A. M., Matsha, T., & Raghubeer, S. (2024). Resveratrol attenuates high glucose-induced inflammation and improves glucose metabolism in HepG2 cells. Scientific Reports, 14(1), 1106. https://doi.org/10.1038/s41598-023-50084-6
van Raalte, D. H., Bjornstad, P., Cherney, D. Z., de Boer, I. H., Fioretto, P., Gordin, D., ... & Heerspink, H. J. (2024). Combination therapy for kidney disease in people with diabetes mellitus. Nature Reviews Nephrology, 20(7), 433-446. https://doi.org/10.1038/s41581-024-00827-z
Vikal, A., Maurya, R., Bhowmik, S., Khare, S., Raikwar, S., Patel, P., & Kurmi, B. D. (2024). Resveratrol: A comprehensive review of its multifaceted health benefits, mechanisms of action, and potential therapeutic applications in chronic disease. Pharmacological Research-Natural Products, 3, 100047. https://doi.org/10.1016/j.prenap.2024.100047
Widiasari, K. R., Wijaya, I. M. K., & Suputra, P. A. (2021). Diabetes Melitus Tipe 2: Faktor Risiko, Diagnosis, dan Tatalaksana. Ganesha Medicine, 1(2), 114. https://doi.org/10.23887/gm.v1i2.40006
Yameny, A. A. (2025). Diabetes Mellitus: A Comprehensive Review of Types, Pathophysiology, Complications, and Standards of Care in Diabetes 2025. Journal of Medical and Life Science, 7(1), 134-141.
Yau, M., Maclaren, N. K., & Sperling, M. A. (2021). Etiology and Pathogenesis of Diabetes Mellitus in Children and Adolescents. MDText.com, Inc.
Yuliana, L. W., Amanah, N. S., & Azelia, N. (2024). Penatalaksanaan Holistik pada Wanita Usia 58 Tahun dengan Neuropati Diabetik dan Hipertensi melalui Pendekatan Dokter Keluarga. Jurnal Penelitian Perawat Profesional, 6(5), 2107–2122. https://doi.org/10.37287/JPPP.V6I5.3165
Yusuf, N. O., Idris, A., Abdulazeez, J., Folorunsho, P. J., Isah, H. A., & Dawud, F. A. (2024). Effect of Resveratrol on Total Protein and Albumin in Type 2 Diabetes Wound Healing in Rats. Mediterranean Journal of Pharmacy and Pharmaceutical Sciences, 4(1), 126–132. https://doi.org/10.5281/zenodo.10827045
Zhang, S., Zhang, S., Zhang, Y., Wang, H., Chen, Y., & Lu, H. (2024). Activation of NRF2 by epiberberine improves oxidative stress and insulin resistance in T2DM mice and IR-HepG2 cells in an AMPK dependent manner. Journal of Ethnopharmacology, 327, 117931. https://doi.org/10.1016/j.jep.2024.117931
Copyright (c) 2025 Journal La Medihealtico
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
