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.