Bifidobacterium longum BL21 probiotic may improve HbA1c when added to metformin in type 2 diabetes
Key takeaway:
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.
Study at a glance
What was studied
Whether adding BL21 probiotic to metformin improves glycemic control in T2DM
Study type
Randomized Controlled Trials (RCTs)
duration
Short-Term (≤3 mo)
Intervention
Probiotics
Outcomes
HbA1c, Fasting Plasma Glucose, Insulin resistance, Triglycerides, Gut microbiota diversity
Funding
Non-industry sponsored
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 Summary
| Intervention | Outcome | Measured Change | Study Effect |
|---|---|---|---|
 Probiotics (Supplements) |  Fasting Plasma Glucose (Glycemic Control) | Decrease | Limited |
Probiotics (Supplements) |  Gut microbiota diversity (Metabolic Health) | Increase | Strong |
Probiotics (Supplements) | HbA1c (Glycemic Control) | Decrease | Strong |
Probiotics (Supplements) | Insulin resistance (Metabolic Health) | Decrease | Limited |
Probiotics (Supplements) | Triglycerides (Metabolic Health) | Decrease | Limited |
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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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Journal Reference
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.
Sources
Ranked by clinical relevance and evidence quality.
Key References
Most relevant evidence and guidance related to this research.
American Diabetes Association Standards of Care in Diabetes—2025: Pharmacologic Approaches to Glycemic Treatment
Supporting Evidence
Supporting evidence and related resources.
Type 2 diabetes in adults: management
A Guide for People with Type 2 Diabetes | American Diabetes Association
Diabetes Diagnosis & Tests | ADA
International Diabetes Federation - IDF Diabetes Atlas 10th Edition
NIH National Center for Complementary and Integrative Health - Probiotics: What You Need To Know
Comparative Efficacy and Safety of Ecnoglutide in Type 2 Diabetes: A Systematic Review and Meta-Analysis.
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