The effect of linagliptin treatment on gut microbiota in patients with HNF1A-MODY or type 2 diabetes - A preliminary cohort study

Abstract

Introduction. Many studies have evaluated the relationship between diabetes and microbiota. In animal models, the dipeptidyl peptidase-4 inhibitors altered the gut microbiota. We investigated whether linagliptin alters the gastrointestinal flora in humans. Materials and methods. This prospective cohort study enrolled 24 patients: 5 patients with maturity onset diabetes of the young associated with HNF1A mutation and 19 patients with type 2 diabetes mellitus. Stool samples were collected at baseline and 4 weeks after treatment intensification with either linagliptin or a sulphonylurea alongside current treatment. Faecal 16S rRNA was analysed by next-generation sequencing. Results. Nine patients initiated linagliptin whereas 15 patients initiated or increased the dose of a sulphonylurea. After linagliptin treatment, we did not observe changes in taxa in L2-L7 based on analysis of composition of microbiomes (ANCOM). The same held true for pairwise alpha diversity (Shannon diversity, p = 0.59; Pielou's measure of evenness, p = 0.68; and observed operational taxonomic units [OTUs], p = 0.77) and beta diversity distances (unweighted UniFrac, p = 0.99; weighted UniFrac, p = 0.93; Bray-Curtis, p = 0.98; and Jaccard, p = 0.99). Similarly, after sulphonylurea intensification, we did not observe changes in taxa in L2-L7 in ANCOM, nor were there changes in alpha diversity (Shannon diversity, p = 0.19; Pielou's measure of evenness, p = 0.21; and observed OTUs, p = 0.42) or beta diversity distances (unweighted UniFrac, p = 0.99; weighted UniFrac, p = 0.99; Bray-Curtis, p = 1; and Jaccard, p = 0.99). Conclusion. We did not observe changes in colonic microbiota 4 weeks after addition of linagliptin to current diabetes treatment. Further studies are required to determine whether linagliptin influences the colonic microbiota in humans.