Exploring the Comparative Efficacy of Metformin and Resveratrol in the Management of Diabetes-Associated Complications: A Systematic Review of Preclinical Studies

Abstract

Food-derived bioactive compounds such as resveratrol are increasingly explored for their protective effects against metabolic complications. Evidence supports the strong antioxidant properties and therapeutic effects of resveratrol in managing diabetes and its associated complications. However, evidence informing on the comparative or combination effects of this natural compound with an accomplished and well-characterized antidiabetic agent like metformin has not been revised. Thus, we conducted a comprehensive systematic search of the major electronic databases which included MEDLINE, Cochrane Library, and EMBASE. The cumulative evidence strongly supports the comparative effects of metformin and resveratrol in ameliorating diabetes-associated complications in preclinical settings. In particular, both compounds showed strong ameliorative effects against hyperglycemia, dyslipidemia, insulin resistance, a pro-inflammatory response, and lipid peroxidation in various experimental models of diabetes. Enhancing intracellular antioxidant capacity in addition to activating NAD-dependent deacetylase sirtuin-1 (SIRT1) and AMP-activated protein kinase (AMPK) are the prime mechanisms involved in the therapeutic effects of these compounds. Of interest, preclinical evidence also demonstrates that the combination treatment with these compounds may have a greater efficacy in protecting against diabetes. Thus, confirmation of such evidence in well-organized clinical trials remains crucial to uncover novel therapeutic strategies to manage diabetes and its linked complications.

Resveratrol Improves Bnip3-Related Mitophagy and Attenuates High-Fat-Induced Endothelial Dysfunction

“…At nutritionally relevant concentrations, resveratrol increases antioxidative enzyme gene expression and inhibits transcription of proinflammatory cytokines (Lejri et al, 2019;Rao et al, 2019). Previous studies have shown resveratrol promotes glucose metabolism as an adjunctive therapy for the management of diabetes-associated complications (Dludla et al, 2020). Additionally, resveratrol accelerates white adipocyte tissue browning (Li et al, 2020b) and fatty acid oxidation (Zhang et al, 2019d).…”

A Meta-Analysis of the Impact of Resveratrol Supplementation on Markers of Renal Function and Blood Pressure in Type 2 Diabetic Patients on Hypoglycemic Therapy

“…Dietary supplements and functional food ingredients are increasingly being explored for their diverse therapeutic capabilities [18,42,43]. As such, several dietary supplements have gained special interest due to their envisaged ameliorative effects against lifestyle diseases such as T2D and cardiovascular complications [17][18][19]23,24,29].…”

“…Resveratrol is a non-flavonoid polyphenol that naturally occurs as phytoalexin and has been extensively studied in animal models and in diabetic humans [20,43,47]. This explains the general interest in understanding the therapeutic benefits of dietary supplements such as resveratrol in improving human health, especially their synergistic effects when used with established oral glucose-lowering drugs like metformin.…”

Pharmaceutical Drugs and Natural Therapeutic Products for the Treatment of Type 2 Diabetes Mellitus

“…The antidiabetic synergistic effects of biguanides with certain natural substances have been determined. Several studies suggest a synergistic impact of resveratrol and metformin [ 234 ]. Furthermore, decreased blood glucose levels have been observed in STZ-induced diabetic rats receiving garlic extract in combination with metformin [ 235 ].…”