How the GLP-1 Drug Dulaglutide Changes Gut Bacteria Over 48 Weeks in People With Type 2 Diabetes | Research

The takeaway

Dulaglutide significantly altered gut microbiome composition after 48 weeks of treatment in newly diagnosed type 2 diabetes patients, suggesting gut bacteria may be part of how the drug works.

48 weeks to see gut changes
No significant microbiome shifts after 1 week, but major compositional changes emerged after 48 weeks of dulaglutide treatment

What the researchers found

After 48 weeks of dulaglutide administration, the composition of intestinal flora changed significantly in newly diagnosed T2DM patients, with a notable reduction in overall bacterial abundance. No significant changes were observed after just 1 week of treatment.

Fasting glucose levels, fasting C-peptide levels, HbA1c levels, and BMI were all found to be closely associated with changes in intestinal flora composition, suggesting that gut microbiome modulation may be one of the mechanisms through which dulaglutide treats type 2 diabetes.

Why it matters

GLP-1 receptor agonists like dulaglutide are among the most widely prescribed diabetes drugs, and understanding all the ways they work is important for optimizing treatment. This study suggests that beyond their known effects on insulin and blood sugar, these drugs may also work partly by reshaping the gut microbiome — opening up new avenues for understanding and improving diabetes treatment.

How the study worked

Researchers used 16S rRNA amplicon sequencing — a DNA-based technique for identifying bacterial species — to analyze stool samples from newly diagnosed type 2 diabetes patients. Samples were collected before treatment, after 1 week, and after 48 weeks of dulaglutide administration. The team then correlated microbiome changes with metabolic markers including fasting glucose, C-peptide, HbA1c, and BMI.

What this study cannot tell us

This was a preliminary study with a relatively small sample size of newly diagnosed patients only. The study used 16S rRNA sequencing, which identifies bacteria at a broad level but may miss functional details. It was a longitudinal observational design, so it cannot prove that dulaglutide directly caused the microbiome changes — other factors like diet changes during treatment could contribute. No control group receiving placebo was mentioned.

How to read the evidence

This is a preliminary longitudinal study in humans, which is stronger than animal research, but the small sample size and lack of a control group limit the strength of the conclusions. It establishes a correlation between dulaglutide use and microbiome changes, not causation.

When this study was published

Published in 2024, this is a recent study reflecting current interest in the gut microbiome's role in GLP-1 drug mechanisms.

The bigger picture

There is growing recognition that the gut microbiome plays a central role in metabolic diseases like type 2 diabetes. This study adds to a body of evidence suggesting that GLP-1 receptor agonists — already blockbuster drugs for diabetes and obesity — may exert some of their benefits through the gut-brain-microbiome axis. Understanding this connection could lead to combination therapies or microbiome-targeted approaches that enhance GLP-1 drug efficacy.

Questions still open

Do the gut microbiome changes caused by dulaglutide contribute to its blood sugar-lowering effects, or are they a secondary consequence?
Would combining dulaglutide with probiotics or other microbiome interventions enhance its diabetes treatment effects?
Do other GLP-1 receptor agonists like semaglutide produce similar gut microbiome changes?

Common questions

Does dulaglutide change your gut bacteria?

According to this study, yes — but it takes time. After 1 week of treatment, no significant changes were seen. After 48 weeks, however, there were major shifts in the types and amounts of gut bacteria, suggesting dulaglutide has a gradual effect on the microbiome.

Could gut bacteria be part of how GLP-1 drugs work for diabetes?

This study suggests it's possible. The researchers found that metabolic markers like blood sugar and HbA1c were closely linked to gut flora changes during dulaglutide treatment, hinting that microbiome modulation may be one mechanism — alongside the drug's known effects on insulin and glucagon.

Read the original research

Correlation between intestinal flora and GLP-1 receptor agonist dulaglutide in type 2 diabetes mellitus treatment-A preliminary longitudinal study.

iScience, 27(5), 109784

View on PubMed ↗Publisher’s paper ↗

Citation

Liang, Lei; Su, XiaoYun; Guan, Yaxin; Wu, Bin; Zhang, Xuxiang; Nian, Xin. (2024). Correlation between intestinal flora and GLP-1 receptor agonist dulaglutide in type 2 diabetes mellitus treatment-A preliminary longitudinal study.. iScience, 27(5), 109784. https://doi.org/10.1016/j.isci.2024.109784