Gut Microbiome

Fecal microbiome predicts treatment response after the initiation of semaglutide or empagliflozin uptake.

TL;DR

Semaglutide and empagliflozin use is associated with changes in the gut microbiome after treatment initiation, and the baseline gut microbiome predicted changes in glycohemoglobin for both semaglutide and empagliflozin users.

Key Findings

Semaglutide and empagliflozin initiation was associated with changes in gut microbial community composition, but not in microbial diversity.

  • Changes in the gut microbiome were detected following initiation of both semaglutide and empagliflozin.
  • No significant changes in microbial diversity (alpha or beta diversity) were observed after treatment initiation.
  • Gut microbiome samples were collected at four timepoints: Baseline, Month 1, Month 3, and Month 12.
  • 16S ribosomal RNA gene sequencing was used to characterize the gut microbiome.

The baseline gut microbiome predicted changes in glycohemoglobin (HbA1c) for both semaglutide and empagliflozin users.

  • Pre-treatment gut microbiome composition was associated with subsequent treatment efficacy as measured by changes in glycohemoglobin.
  • This predictive relationship was observed in both drug groups.
  • Pearson correlation was used to identify microbial features associated with the change in clinical parameters.
  • Clinical markers including glycohemoglobin were quantitatively measured before treatment initiation and at Months 3 and 12.

The study design involved type 2 diabetes patients providing fecal, plasma, and urine samples at multiple timepoints during treatment with semaglutide or empagliflozin.

  • Patients donated gut microbiome fecal samples at four timepoints: Baseline, Month 1, Month 3, and Month 12.
  • Plasma and urine samples were collected for quantitative measurement of clinical markers before treatment initiation and at Months 3 and 12.
  • Repeated measures ANOVA paired with paired t-tests were used to analyze the effects of drug initiation on the gut microbiome.
  • The study focused on patients with type 2 diabetes initiating either semaglutide or empagliflozin.

Both semaglutide and empagliflozin impacted the gut microbial community during the treatment period.

  • Specific microbial taxa were altered following initiation of semaglutide and empagliflozin.
  • The bidirectional effects of these novel type 2 diabetes drugs and the gut microbiome had not been clearly described prior to this study.
  • The interaction between medications and the gut microbiome was investigated as potentially bidirectional, consistent with findings for other diabetes medications.

The baseline gut microbiome was identified as a potential predictor of semaglutide treatment effects specifically.

  • The authors concluded that 'the baseline gut microbiome can predict semaglutide treatment effects.'
  • Pre-treatment microbial features were correlated with clinical outcomes using Pearson correlation analysis.
  • This finding suggests a role for the gut microbiome in modulating individual responses to semaglutide therapy.

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Citation

Klemets A, Reppo I, Krigul K, Volke V, Aasmets O, Org E. (2026). Fecal microbiome predicts treatment response after the initiation of semaglutide or empagliflozin uptake.. Scientific reports. https://doi.org/10.1038/s41598-026-36318-3