Resveratrol as Add-on Therapy in Subjects With Well-Controlled Type 2 Diabetes: A Randomized Controlled Trial

Diabetes Care. 2016 Dec;39(12):2211-2217. doi: 10.2337/dc16-0499. Epub 2016 Oct 6.


Objective: To determine whether resveratrol supplementation can improve insulin sensitivity and promote overall metabolic health on top of standard diabetes care.

Research design and methods: Seventeen subjects with well-controlled type 2 diabetes (T2D) were treated with placebo and 150 mg/day resveratrol (resVida) in a randomized double-blind crossover study for 30 days. The main outcome measure was insulin sensitivity by the hyperinsulinemic-euglycemic clamp technique.

Results: Hepatic and peripheral insulin sensitivity were not affected by resveratrol treatment. Intrahepatic lipid content also remained unaffected by resveratrol; however, the change in intrahepatic lipid content correlated negatively with plasma resveratrol levels (R = -0.68, P = 0.03). Intramyocellular lipid content increased in type 2 muscle fibers (P = 0.03), and systolic blood pressure tended to decrease (P = 0.09) upon resveratrol treatment. In addition, resveratrol significantly improved ex vivo mitochondrial function (state 3 and state U respiration upon malate with octanoyl-carnitine, P < 0.005). Intriguingly, a correlation was found between plasma levels of a metabolite of resveratrol (dihydroresveratrol) and the metformin dose used by the patients (R = 0.66, P = 0.005), suggesting an interaction between metformin and resveratrol. It could be speculated that the lack of a resveratrol-induced insulin-sensitizing effect is caused by this interaction.

Conclusions: Resveratrol supplementation does not improve hepatic or peripheral insulin sensitivity. Our results question the generalized value of resveratrol as an add-on therapy in the treatment of T2D and emphasize the need to perform studies in drug-naive patients with T2D or subjects with prediabetes.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / metabolism
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Double-Blind Method
  • Drug Therapy, Combination
  • Glucose Clamp Technique
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Insulin / administration & dosage
  • Insulin / adverse effects
  • Insulin Resistance / physiology
  • Male
  • Metformin / administration & dosage*
  • Metformin / adverse effects
  • Middle Aged
  • Resveratrol
  • Stilbenes / administration & dosage*
  • Stilbenes / adverse effects
  • Stilbenes / metabolism
  • Stilbenes / pharmacokinetics


  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Stilbenes
  • dihydroresveratrol
  • Metformin
  • Resveratrol