Semaglutide treatment alleviated glucose metabolism disorders and improved cardiac dysfunction in diabetic mice. Additionally, semaglutide reduced oxidative stress and apoptosis in diabetic hearts, activated the SIRT1/AMPK pathway, and restored Cx43 expression, which had been reduced in diabetic mouse myocardium. ECG abnormalities, such as significantly prolonged RR, QRS, QT, and QTc intervals, were reversed following semaglutide treatment. Here, GJA1 is linked to glucose metabolism disease.