Bifidobacterium longum BL21 probiotic may improve HbA1c when added to metformin in type 2 diabetes
Last updated May 4, 2026
Key finding
A 12-week double-blind RCT in adults with T2DM found that adding Bifidobacterium longum BL21 to metformin significantly lowered HbA1c by 0.3% and favorably shifted gut microbiota compared to placebo.
This double-blind study tested whether a specific probiotic strain, Bifidobacterium longum BL21, could improve blood sugar control in people with type 2 diabetes already taking metformin. After 12 weeks, those who added the probiotic had a small but meaningful drop in HbA1c compared to placebo, along with beneficial changes in their gut bacteria. No serious side effects occurred.
Quick read
Study at a glance
The essential study design details in one scan.
EvidenceScore™
Moderate
Study type
Randomized Controlled Trials (RCTs)
Follow-up
Short-Term (≤3 mo)
Risk of bias
Some Concerns
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Plain-language summary
What this paper says
A plain-language read of the study’s main message and where it applies.
Study focus
A 12-week double-blind RCT in adults with T2DM found that adding Bifidobacterium longum BL21 to metformin significantly lowered HbA1c by 0.3% and favorably shifted gut microbiota compared to placebo.
Published in
Journal Reference
Publication details and source links for this paper.
Zhu C, Liu Y, Chen Y, et al. Probiotic Supplementation With Bifidobacterium longum Subsp. Longum BL21 Improves Glycemic Control and Modulates Gut Microbiota in Type 2 Diabetes: A Randomized Controlled Trial. Food Sci Nutr. 2026;14(1):e71437.
Main Effects
↓ HbA1c (0.3% reduction vs placebo, p=0.026, meeting ADA MCID threshold)
↑ Beneficial gut bacteria (Bifidobacterium, Faecalibacterium enriched)
→ Fasting glucose, insulin resistance, triglycerides showed non-significant improvement trends
Evidence Suggest
- BL21 significantly reduced HbA1c compared to placebo as an adjunct to metformin (p=0.026)
- Favorable gut microbiota changes with increased SCFA-producing genera and reduced pathogenic taxa
- Safety profile comparable to placebo with no serious adverse events reported
Who this applies to
Adults with type 2 diabetes currently taking metformin who have room for improvement in their blood sugar control and are interested in evidence-based probiotic options as a supportive therapy.
Keep in Mind
The HbA1c reduction of 0.3% is modest compared to prescription diabetes medications. The non-significant findings for fasting glucose and insulin resistance suggest not all metabolic parameters benefited. The study was also relatively small and short, so larger and longer trials are needed to confirm whether this effect lasts and who benefits most.
Between the Lines
- Small sample size without formal a priori power calculation
- 12-week duration may not capture long-term efficacy or sustainability
- Gut microbiota analysis was taxonomic/descriptive without direct SCFA measurement
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