Dibifree, a dietary phytomix, improves glycemic control and adiposity via modulation of the gut-pancreas-adipose-immune axis in type 2 diabetes.

Dibifree as add-on therapy significantly reduced HbA1c compared with placebo in a randomized controlled trial.

• Study design: 7-month randomized, double-blind, placebo-controlled crossover trial with 40 adults with T2D.
• Dibifree was administered at 15 g/day as add-on therapy for two 3-month sessions separated by a 1-month wash-out.
• HbA1c was a primary endpoint and was significantly reduced compared to placebo.
• Effects were sustained after wash-out and upon re-challenge with Dibifree.

Dibifree significantly reduced fasting and postprandial glucose compared with placebo.

• Fasting glucose and postprandial glucose were both primary endpoints.
• Reductions were statistically significant compared to the placebo arm.
• Effects persisted after the wash-out period and were reproduced upon re-challenge.
• The crossover design allowed placebo recipients to switch to Dibifree in the second session, providing additional within-subject comparisons.

Dibifree reduced body fat percentage in T2D patients.

• Body fat percentage decreased in Dibifree-treated subjects.
• Body weight was listed as a primary endpoint alongside glycemic measures.
• Reduction in adiposity was consistent with in vitro findings of suppressed adipogenesis.
• This was observed in the context of an add-on therapy to existing diabetes treatment.

Transcriptomic profiling of Dibifree-treated cell lines revealed reversal of diabetic gene signatures and enrichment of multiple metabolic pathways.

• Pathways enriched included cAMP/GLP-1, insulin secretion, AGE-RAGE, and IL-10 pathways.
• Analysis involved transcriptomic profiling of treated cell lines followed by pathway enrichment analyses.
• Results indicated a reversal of diabetic gene expression signatures.
• These findings provided a mechanistic basis for the multi-target effects of Dibifree.

Dibifree demonstrated enhanced GLP-1 secretion and inhibition of DPP-4 and α-glucosidase in functional assays.

• Incretin activity was assessed via in vitro assays showing enhanced GLP-1 secretion.
• DPP-4 inhibition was confirmed, which would prolong endogenous GLP-1 activity.
• α-glucosidase inhibition was demonstrated, consistent with delayed carbohydrate absorption.
• Improved glucose tolerance was also observed in T2D mice in vivo.

Dibifree reduced advanced glycation end-product (AGE) formation in functional assays.

• Inhibition of AGE formation was demonstrated in vitro.
• This activity corresponded to enrichment of the AGE-RAGE pathway in transcriptomic analyses.
• Reduction of AGE formation is relevant to prevention of diabetic complications.
• This was one of several multi-target mechanisms identified for Dibifree.

Dibifree suppressed adipogenesis and promoted M2 macrophage polarization in functional assays.

• In vitro assays demonstrated suppression of adipogenesis, consistent with the observed reduction in body fat percentage in clinical participants.
• Promotion of M2 macrophage polarization was demonstrated, indicating an anti-inflammatory immune modulation effect.
• These findings corresponded to IL-10 pathway enrichment in transcriptomic analyses.
• These mechanisms were described as relevant to metabolic and immune regulation in T2D.

Dibifree was formulated as a dietary phytomix using food-derived anti-diabetic bioactivities and administered at 15 g/day.

• Dibifree was developed by integrating dietary and therapeutic strategies for T2D management.
• The dose was 15 g/day administered as add-on therapy to existing treatments.
• The product is described as a functional food intervention.
• Mechanistic studies used integrated bioinformatics and functional assays to elucidate the basis of its effects.