Gut microbiota in subjects with prediabetes has a low mediating effect on the hypoglycemic outcome of linagliptin/metformin and metformin.

Abstract

Abstract Lifestyle modifications, metformin, and linagliptin reduce the incidence of type 2 diabetes (T2D) in people with prediabetes. The efficacy of such interventions may be enhanced by the gut microbiota (GM), which mediate glucose-lowering effects through short-chain fatty acids (SCFA). We determined the effect of combined linagliptin/metformin vs metformin monotherapy on GM composition and its relationship to insulin sensitivity (IS) and pancreatic β-cell function (Pβf) in patients with prediabetes without previous treatment. A double-blind, randomized parallel clinical trial was conducted in 167 Mexican adults for 12 months. These treatments increased the abundance of GM SCFA-producing bacteria (Metformin (Fusicatenibacter and Blautia) and Linagliptin/metformin (Roseburia, Bifidobacterium and [Eubacterium] hallii group). We performed a mediation analysis with two structural equation models (SEM). SEM shows that bacterial genera are weakly associated with IS and Pβf. Therefore, metabolic improvements observed with these interventions are due to a greater extent to the antidiabetic drug's effect.