Bifidobacterium longum BL21 probiotic may improve HbA1c when added to metformin in type 2 diabetes

Moderate confidence

some concerns bias

Last updated May 4, 2026

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.