Diabetes mellitus (DM), and its micro and macrovascular complications, is one of the
biggest challenges for world public health. Despite overall improvement in prevention, diagnosis and
treatment, its incidence is expected to continue increasing over the next years. Nowadays, finding
therapies to prevent or retard the progression of diabetic complications remains an unmet need
due to the complexity of mechanisms involved, which include inflammation, oxidative stress and
angiogenesis, among others. Flavonoids are natural antioxidant compounds that have been shown
to possess anti-diabetic properties. Moreover, increasing scientific evidence has demonstrated their
potential anti-inflammatory and anti-oxidant effects. Consequently, the use of these compounds
as anti-diabetic drugs has generated growing interest, as is reflected in the numerous in vitro
and in vivo studies related to this field. Therefore, the aim of this review is to assess the recent
pre-clinical and clinical research about the potential effect of flavonoids in the amelioration of diabetic
complications. In brief, we provide updated information concerning the discrepancy between the
numerous experimental studies supporting the eficacy of flavonoids on diabetic complications and
the lack of appropriate and well-designed clinical trials. Due to the well-described beneficial effects
on different mechanisms involved in diabetic complications, the excellent tolerability and low cost,
future randomized controlled studies with compounds that have adequate bioavailability should be evaluated as add-on therapy on well-established anti-diabetic drugsThis paper was not funded. The authors work has been supported by FEDER-ISCIII Funds (PI17/00130,
PI17/01495), Spanish Ministry of Economy and Competitiveness (RTI2018-098788-B-100, DTS17/00203, DTS19/00093,
RYC-2017-22369), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN) and Spanish Society
of Atherosclerosis (SEA). TCO is an employee of FAES Pharma. The authors (except JAM) have an ongoing
research project in common with FAES Pharma on Flavonoids in diabetic complications under the auspices of the
joint-RETOS Collaborations Project 2017 (RTC-2017-6089-1), program supported by Spanish Ministry of Economy and Competitiveness