Abstract: Metformin is a first-line treatment for type 2 diabetes (T2D) due to its excellent blood glucose-lowering effects, safety, and multiple metabolic benefits. However, significant side effects related to dosages are also observed in clinical practice. Therefore, reducing the dosage while achieving satisfactory glycemic control becomes a crucial step in optimizing clinical treatment. Recent studies have shown that static magnetic fields (SMFs) have certain ameliorative effects on diabetic mice, but the combinational effects of SMFs and hypoglycemic agents are still unknown. In this study, the effects on high-fat diet and streptozotocin-induced T2D mice by combining a downward, moderate-intensity SMF with metformin were investigated. The fasting blood glucose, glucose tolerance, GLP-1 levels, and insulin secretion were all assessed. The results revealed that although the antihyperglycemic effect of SMF combined with lower-dose metformin (150 mg/kg) was not greater than that of higher-dose metformin (250 mg/kg), it was superior to SMF or low-dose metformin alone. Furthermore, 16S rRNA gene sequencing analysis of intestinal contents revealed that the abundance ofRuminococcusandAdlercreutzia, which were positively related to diabetes, were significantly decreased by the combinational treatment of SMF and metformin. The abundance of probiotics such asLactobacillusandOscillospirawere also increased after SMF exposure. Therefore, this study showed that this type of SMF could improve the intestinal microflora of diabetic mice and enhance the hypoglycemic effect of low-dose metformin, which could potentially provide a new feasible, safe and effective combination strategy for the treatment of diabetes

Key words: diabetes, static magnetic fields, metformin, gut microbiota, combined treatment