Comparative evaluation of dulaglutide alone vs. dulaglutide combined with probiotics on cardiovascular risk factors in T2DM.

OBJECTIVE: This randomized controlled trial aimed to compare the effects of dulaglutide alone versus dulaglutide combined with probiotics on cardiovascular risk factors, pancreatic beta-cell function, and gut microbiota in patients with type 2 diabetes mellitus (T2DM). METHODS: Sixty overweight/obese adults with T2DM (HbA1c 6.5-11%, BMI ≥ 24 kg/m²) were randomized to a control group (dulaglutide 1.5 mg/week + placebo) or an intervention group (dulaglutide 1.5 mg/week + probiotics containing Bifidobacterium longum, 2 × 10⁹ CFU/dose) for 12 weeks. Outcomes included glycemic control (HbA1c, fasting plasma glucose [FPG], 2-hour postprandial glucose [2hPG]), inflammatory markers (TNF-α, CRP), cardiovascular risk factors (blood pressure, lipids), gut microbiota, and safety. RESULTS: The intervention group showed greater reductions in HbA1c (- 1.06% vs. -0.35%, P = 0.028), FPG (- 4.16 vs. -3.92 mmol/L, P = 0.010), and inflammatory markers (TNF-α: -43.6% vs. -33.3%, P < 0.001). Pancreatic beta-cell function improved significantly (HOMA-β: +34.7% vs. +23.1%, P = 0.034), with increased beneficial gut microbiota (Lactobacillus: +2.1 × 10⁶ vs. +1.3 × 10⁶ CFU/g, P < 0.001). Hypertension incidence (0% vs. 13.3%, P = 0.038) and dyslipidemia (0% vs. 16.7%, P = 0.020) were lower in the intervention group. Both regimens were well-tolerated, with no severe hypoglycemia or renal/hepatic toxicity. CONCLUSION: Combining dulaglutide with probiotics enhances glycemic control, reduces inflammation, and improves cardiovascular risk factors in T2DM more effectively than dulaglutide alone, likely through gut microbiota modulation. This dual approach offers a promising strategy for T2DM management, though larger long-term trials are needed to confirm cardiovascular benefits.