Totum-63, a plant-based polyphenol-rich extract, in prediabetes or early-stage type 2 diabetes: an international, multicenter, randomized controlled trial.

This multicenter, parallel-arm, superiority, randomized, double-blind, placebo-controlled study evaluates the efficacy of Totum-63 (T63), a polyphenol-rich blend of plant extracts, in improving fasting plasma glucose (FPG) in individuals with prediabetes or early-stage type 2 diabetes (T2D). Individuals from seven European countries with FPG between 110-220 mg/dL were randomized to receive placebo (PBO, n = 210), T63 (5 g/d) distributed thrice daily (T63 TID, n = 212) or twice daily (T63 BID, open-label arm, n = 214) over six months. Individuals were randomly assigned using a dynamic randomization algorithm, stratified by their glycemic status at baseline (FPG < 126 mg/dL or FPG ≥ 126) and the investigational site country. The primary outcome was the FPG change in T63 TID compared to PBO in the intention-to-treat population. Secondary assessments included changes in diabetes biomarkers, lipid profile, anthropometric measurements and subpopulation analyses based on glycemic status. During the whole study, neither the investigators nor the subjects were aware of the product they tested, except in the open arm. After six months, FPG was significantly reduced in the T63 TID group (PBO-adjusted mixed model estimated difference, PBO-AD = -3.8 mg/dL, 95% CI: [-5.9; -1.7], p = 0.0149) and the T63 BID group (PBO-AD = -5.5 mg/dL, 95% CI: [-9.7; -1.3] p < 0.001). Hence, T63 may represent a non-pharmaceutical strategy for T2D prevention. ClinicalTrials.gov Identifier: NCT04423302. Funding: This trial was funded by Valbiotis®.