Objective To investigate the effects of liraglutide on the gut microbiota of db/db diabetic mice and the predictive value of the microbial structure for the hypoglycemic efficacy.

Methods The db/db mice were randomly divided into control group and liraglutide group (0.4 μg/g). Fasting blood glucose levels were measured in the mice, and fecal samples were collected to determine the structure of the gut microbiota.

Results Compared with the control group, the liraglutide group exhibited a significant increase in the average number of operational taxonomic unit (OTU) (P < 0.01). The number of observed species, Chao1 index and ACE index were all significantly higher in the liraglutide group than those in the control group (P < 0.05). Additionally, the liraglutide group showed a significant increase in the relative abundance of Firmicutes and a significant decrease in the abundance of Actinobacteria compared with the control group (P < 0.01). The percentage decrease in blood glucose levels in db/db mice was positively correlated with the abundance of Pseudomonadaceae and negatively correlated with the abundances of Clostridiaceae and Peptostreptococcaceae.

Conclusion Liraglutide treatment can modulate the structure of the gut microbiota, increasing the number of OTU and diversity, particularly enhancing the abundance of beneficial bacteria such as Clostridium, Lachnospira and Oscillospira. The gut microbiota structure in mice serves as a predictive factor for the hypoglycemic efficacy of liraglutide, with diabetic mice exhibiting a higher abundance of Pseudomonas being more likely to benefit from liraglutide-induced hypoglycemic therapy.