Effect of probiotics derivatives (postbiotics and metabiotics) on glycemic control in individuals with type 2 diabetes: a randomized clinical trial (DELI_Diab study)

Introduction: Probiotics have demonstrated positive effects on obesity and type 2 diabetes (T2D) in various studies. Postbiotics, specifically nonliving bacterial lysates derived from cell walls and DNA, are increasingly recognized as safe, stable, and effective alternatives for improving host metabolic health. Aim: DV - NRRL B-68023 as an adjunct to standard antidiabetic therapy. Material and methods: lysate twice daily or a matching placebo. Blinding was ensured through identical masked packaging. The primary efficacy analysis was performed on a per-protocol (PP) population of 42 participants (intervention, n=20; placebo, n=22) who completed the 3-month treatment and 3-month follow-up. Primary endpoints were HbA1c and fasting plasma glucose (FPG). Secondary endpoints included HOMA-2 modeled insulin sensitivity (%S), β-cell function (%B), and anthropometric parameters, evaluated at baseline, 3, and 6 months. The trial was registered at ClinicalTrials.gov (NCT05770076). Results: The primary analysis revealed a significant overall treatment effect for HbA1c (p<0.001). After 3 months, the intervention group showed a mean HbA1c reduction of -0.63% (95% CI: -0.98 to -0.28), while the placebo group significantly worsened (0.50%; 95% CI: 0.17 to 0.84). For FPG, a favorable between-group trend was observed (p=0.086), with a reduction of 1.32 mmol/L in the active group compared to an increase of 0.12 mmol/L in the placebo group. Exploratory analysis showed significant treatment effects for waist circumference (p = 0.021) and insulin sensitivity (%S, p = 0.013). Although within-group improvements were noted for BMI and β-cell function (%B) in the intervention group (p<0.05), between-group differences for these parameters were not statistically significant (p>0.05). Conclusions: lysate significantly improves glycemic control (HbA1c) and reduces waist circumference compared to placebo in T2D patients. While positive trends in insulin sensitivity and anthropometrics were observed, further large-scale studies are required to confirm these metabolic benefits and assess long-term sustainability. Clinical Trial Registration: https://clinicaltrials.gov/keywords, identifier NCT05770076.