Gut microbiome differences between metformin- and liraglutide-treated T2DM subjects.

INTRODUCTION

Metformin and glucagon-like peptide-1 (GLP-1) agonists are widely used for treating type two diabetes mellitus (T2DM). While recent studies suggest these drugs might modify the gastrointestinal tract (GIT) microbiome, further confirmation is required from human clinical trials.

MATERIALS AND METHODS

Here, we compare, in patients with T2DM, the effects of metformin (n=18 subjects) and liraglutide (n=19), a GLP-1 agonist, on their GIT microbiomes over a 42 day period (n=74 samples) using 16S ribosomal RNA (rRNA) sequencing.

RESULTS

We found that these drugs had markedly different effects on the microbiome composition. At both baseline and Day 42, subjects taking metformin had a significant increase (Baseline adj. =.038, Day 42 adj. =.041) in the relative abundance of the bacterial genus , whereas liraglutide dosing is associated with a significant increase (Baseline adj. =.048, Day 42 adj. =.003) in the genus , a GIT bacteria positively associated with gut barrier homoeostasis. and relative abundances were also significantly associated with duration of subject diabetes (adj <.05). Specifically, there was a significantly higher abundance of in subjects with short and medium durations than those with long duration of diabetes.

DISCUSSION

To our knowledge, this is the first report of GLP-1 agonist-associated changes in the human microbiome and its differentiating effects to metformin. Our study suggests that modulation of the GIT microbiome is a potentially important component in the mechanism of action of these drugs.