Combined effect of interventions with pure or enriched mixtures of (poly)phenols and anti-diabetic medication in type 2 diabetes management: a meta-analysis of randomized controlled human trials

Eur J Nutr. 2020 Jun;59(4):1329-1343. doi: 10.1007/s00394-020-02189-1. Epub 2020 Feb 12.


Purpose: (Poly)phenols have been reported to confer protective effects against type 2 diabetes but the precise association remains elusive. This meta-analysis aimed to assess the effects of (poly)phenol intake on well-established biomarkers in people with type 2 diabetes or at risk of developing diabetes.

Methods: A systematic search was conducted using the following selection criteria: (1) human randomized controlled trials involving individuals with prediabetes and type 2 diabetes; (2) one or more of the following biomarkers: glucose, glycated haemoglobin (HbA1c), insulin, pro-insulin, homeostatic model assessment of insulin resistance (HOMA-IR), islet amyloid polypeptide (IAPP)/amylin, pro-IAPP/pro-amylin, glucagon, C-peptide; (3) chronic intervention with pure or enriched mixtures of (poly)phenols. From 488 references, 88 were assessed for eligibility; data were extracted from 27 studies and 20 were used for meta-analysis. The groups included in the meta-analysis were: (poly)phenol mixtures, isoflavones, flavanols, anthocyanins and resveratrol.

Results: Estimated intervention/control mean differences evidenced that, overall, the consumption of (poly)phenols contributed to reduced fasting glucose levels (- 3.32 mg/dL; 95% CI - 5.86, - 0.77; P = 0.011). Hb1Ac was only slightly reduced (- 0.24%; 95% CI - 0.43, - 0.044; P = 0.016) whereas the levels of insulin and HOMA-IR were not altered. Subgroup comparative analyses indicated a stronger effect on blood glucose in individuals with diabetes (- 5.86 mg/dL, 95% CI - 11.34, - 0.39; P = 0.036) and this effect was even stronger in individuals taking anti-diabetic medication (- 10.17 mg/dL, 95% CI - 16.59, - 3.75; P = 0.002).

Conclusions: Our results support that the consumption of (poly)phenols may contribute to lower glucose levels in individuals with type 2 diabetes or at risk of diabetes and that these compounds may also act in combination with anti-diabetic drugs.

Keywords: Antidiabetic therapy; Diabetes; Glucose; Hb1Ac; Insulin; Polyphenol.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Biomarkers / blood
  • Combined Modality Therapy / methods
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Humans
  • Hypoglycemic Agents / blood*
  • Hypoglycemic Agents / therapeutic use*
  • Phenols / blood*
  • Phenols / therapeutic use*
  • Polyphenols / blood
  • Polyphenols / therapeutic use
  • Randomized Controlled Trials as Topic


  • Biomarkers
  • Hypoglycemic Agents
  • Phenols
  • Polyphenols