Long-term efficacy of dapagliflozin combined with Bifidobacterium triple viable tablets on metabolic syndrome and gut microbiota in overweight/obese patients with type 2 diabetes.

Background: The rising global prevalence of type 2 diabetes (T2D) necessitates innovative therapies targeting glycemic control and metabolic complications. SGLT2 inhibitors improve cardiorenal outcomes and may modulate gut microbiota, while specific probiotics demonstrate glycemic and lipid benefits. However, synergistic effects of combining SGLT2 inhibitors with probiotics remain unexplored.

Methods: This 24-week randomized controlled trial enrolled 120 overweight/obese T2D patients (BMI ≥ 24 kg/m2, HbA1c ≥ 7.0%). Participants were randomized to dapagliflozin (10 mg/day) alone (control, n = 60) or dapagliflozin plus triple viable tablets, containing Bifidobacterium longum, Lactobacillus acidophilus and Enterococcus faecalis (six tablets/day, ≥1.0 × 107 CFU/g/strain; experimental, n = 60). The primary outcome was HbA1c change; secondary outcomes included weight, lipid profiles, blood pressure, gut microbiota (qPCR quantification), and safety. Analyses used mixed-effects models (completers: 57 control, 58 experimental) and Spearman correlations.

Results: The experimental group showed superior improvements in weight (-5.2 kg vs -3.1 kg), HbA1c (-1.8% vs -0.8%), LDL-C (-0.5 vs -0.3 mmol/L), HDL-C (+0.17 vs +0.07 mmol/L), and HOMA-IR (-1.2 vs -0.6) compared to controls (all P < 0.05). Gut microbiota analysis revealed increased Bifidobacterium (7.3 vs 5.5 log CFU/g, P < 0.001), reduced Enterobacteriaceae (4.5 vs 6.5 log CFU/g, P = 0.003), and a higher gram-positive/negative ratio (1.12 vs 0.70, P = 0.001). Bifidobacterium abundance correlated with HbA1c reduction (r = -0.42, P = 0.008), while gram-positive/negative ratio was linked to improved HDL-C (r = 0.26, P = 0.041). Adverse events were comparable between groups (28.3 vs 25.0%, P = 0.672).

Conclusions: Combining dapagliflozin with Bifidobacterium probiotics enhances metabolic outcomes and favorably modulates gut microbiota in T2D patients. These findings support microbiota-targeted adjunctive therapy to optimize SGLT2 inhibitor efficacy.