Role of resveratrol supplementation in regulation of glucose hemostasis, inflammation and oxidative stress in patients with diabetes mellitus type 2: A randomized, placebo-controlled trial.

Randomized, double-blind, placebo-controlled parallel-group trial in adults with type 2 diabetes aged 18-70 years who had been using oral hypoglycemic agents for at least 1 year, with HbA1c 7-12% and BMI at or below 35 kg/m2. In the resveratrol arm, 55 participants were randomized and 45 completed the study.

Resveratrol 200 mg was taken orally once daily as a capsule with breakfast for 24 weeks, added to ongoing oral hypoglycemic therapy. The active product was 99% pure trans-resveratrol; placebo capsules contained cellulose.

Resveratrol improved glycemic control and insulin resistance versus placebo over 24 weeks, while also reducing inflammatory and oxidative stress markers and favorably modulating circulating microRNAs. Compared with placebo, FPG fell by -0.50 (95% CI -0.94 to -0.06; p = 0.016), HbA1c by -0.45 (-0.88 to -0.02; p = 0.033), insulin by -1.31 (-2.24 to -0.38; p = 0.001), and HOMA-IR by -0.83 (-1.37 to -0.29; p = 0.001). hs-CRP (-0.35), IL-6 (-1.99), TNF-α (-1.25), MDA (-0.36), and microalbuminuria (-0.67) also improved, whereas lipid outcomes did not change significantly. miRNA-34a-5p, miRNA-375-3p, miRNA-21-5p, and miRNA-192-5p were downregulated, while miRNA-126-3p and miRNA-132-3p were upregulated. No adverse effects were reported.

The trial was relatively small in the active arm and lasted only 24 weeks, which limits confidence in durability and generalizability. Fewer participants completed the resveratrol arm than were randomized, and the intervention was tested only as an adjunct to oral hypoglycemic therapy in a single-country setting.