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

Recognizing the potential of integrating dietary and therapeutic strategies for type 2 diabetes management, Dibifree was developed as a dietary phytomix formulated with food-derived anti-diabetic bioactivities. This study aimed to evaluate the add-on efficacy of Dibifree in T2D patients and to elucidate its mechanistic basis via integrated bioinformatics and functional assays. In a 7-month randomized, double-blind, placebo-controlled crossover trial, 40 adults with T2D received Dibifree (15 g/day) or placebo as add-on therapy for two 3-month sessions separated by a 1-month wash-out, with placebo recipients switched to Dibifree in the second session. Primary endpoints included fasting and postprandial glucose, HbA1c, and body weight. Mechanistic studies involved transcriptomic profiling of treated cell lines, pathway enrichment analyses, and in vitro/in vivo assays on incretin activity, glycation, adipogenesis, and immune modulation. Dibifree as an add-on therapy significantly reduced HbA1c, fasting, and postprandial glucose compared with placebo, with sustained effects after wash-out and re-challenge. Body fat percentage also decreased. Transcriptomic analysis revealed reversal of diabetic gene signatures and enrichment of cAMP/GLP-1, insulin secretion, AGE–RAGE, and IL-10 pathways. Functional assays demonstrated multiple bioactivities, including enhanced GLP-1 secretion, inhibition of DPP-4 and α-glucosidase, and improved glucose tolerance in T2D mice, as well as reduced AGE formation, suppressed adipogenesis, and promotion of M2 macrophage polarization. Dibifree, as a functional food intervention, improved glycemic control and reduced adiposity in T2D patients, with evidence supporting multi-target mechanisms relevant to metabolic and immune regulation.