Effects of empagliflozin alone and in combination with exercise on the soleus muscle in obese type 2 diabetic rats

This study assessed whether empagliflozin (EMPA) combined with endurance exercise further improves the soleus muscle in spontaneously diabetic Torii fatty rats, a model of obese type 2 diabetes. Male rats were divided into untreated control, exercise, EMPA, or EMPA + exercise groups. Age-matched Sprague-Dawley rats served as nondiabetic controls. Treadmill training and EMPA (0.03% in chow) were provided from 8 to 16 weeks of age. Both EMPA and the combined intervention improved blood glucose and insulin resistance. Additionally, the combined treatment reduced total cholesterol and triglycerides compared with EMPA alone. The cross-sectional area of type I fibers in the soleus tended to improve with all interventions. Combination treatment significantly enhanced citrate synthase activity, mitochondrial functional protein expression, and autophagic flux. These findings suggest that although EMPA does not adversely affect the soleus muscle, combining it with endurance exercise confers superior benefits via improved mitochondrial status, autophagy, and lipid metabolism.