A Northwestern University-led preclinical study in mice found metformin’s glucose-lowering effects are driven primarily by gut cell biology rather than liver-centric mechanisms. In Nature Metabolism, the team reported that metformin inhibits mitochondrial complex I in intestinal epithelium, slowing mitochondrial energy production and promoting glycemic control. By reducing mitochondrial activity, the gut behaves as a glucose sink, increasing intestinal glucose utilization and mitigating postprandial blood sugar rises in the study model. The researchers also reported that phenformin and berberine appear to engage the same gut pathway. The work broadens the mechanistic foundation for biguanide drugs and suggests gut mitochondrial modulation may represent a viable strategy for blood sugar control—potentially informing future therapeutic combinations and biomarker approaches.