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

Johan Louw,Tawanda M Nyambuya,Sithandiwe E Mazibuko-Mbeje,Sonia Silvestri,Patrick Orlando,Bongani B Nkambule,Kwazi B Gabuza,Kabelo Mokgalaboni,Christo J F Muller,Vuyolwethu Mxinwa,Rabia Johnson,Luca Tiano,Phiwayinkosi V Dludla

doi:10.3390/nu12030739

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.

Highlights

It has been centuries since diabetes mellitus was first described [1], this metabolic condition continues to greatly impact the quality of life of patients living with diabetes [2,3]
93 studies were initially excluded for being relevant, as much as 26 studies were disregarded because they were reviews, letters to the editor or they did not report on diabetes
Food-derived bioactive compounds are increasingly explored for their ameliorative effects against metabolic diseases

Summary

Introduction

It has been centuries since diabetes mellitus was first described [1], this metabolic condition continues to greatly impact the quality of life of patients living with diabetes [2,3]. Besides being one of the top ten causes of death worldwide [4], patients with diabetes are at an increased risk of comorbidity of complications associated with metabolic disorders such as neuropathy, retinopathy, and cardiovascular diseases (CVDs). These comorbidities significantly reduce the quality of life, and may even accelerate the rate of permanent disability [5,6]. Diabetes is often described in terms of its impact on working-age adults, it is of concern that even in older adults (≥60 years old), this condition accelerates the rate of mortality, while enhancing the risk of institutionalization [7]. The pathological mechanisms implicated in the development of diabetes have been partially described [10,11,12], long-term effective therapeutic strategies to contain this metabolic disorder remain scarce

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Conclusion