Insulin resistance has been shown to be associated with cardiac sympathovagal imbalance, myocardial dysfunction, and cardiac
mitochondrial dysfunction. Whereas
metformin is a widely used
antidiabetic drug to improve
insulin resistance,
vildagliptin is a novel oral
antidiabetic drug in a group of dipeptidyl peptidase-4 inhibitors in which its cardiac effect is unclear. This study aimed to determine the cardiovascular effects of
metformin and
vildagliptin in rats with
insulin resistance induced by high-fat diet. Male Wistar rats were fed with either a normal diet or high-fat diet (n =24 each) for 12 wk. Rats in each group were divided into three subgroups to receive the vehicle,
metformin (30 mg/kg, twice daily), or
vildagliptin (3 mg/kg, once daily) for another 21 d. Heart rate variability (HRV), cardiac function, and cardiac mitochondrial function were determined and compared among these treatment groups. Rats exposed to a high-fat diet developed increased
body weight, visceral fat, plasma
insulin,
cholesterol, oxidative stress, depressed HRV, and cardiac
mitochondrial dysfunction.
Metformin and
vildagliptin did not alter
body weight and plasma
glucose levels but decreased the plasma
insulin, total
cholesterol, and oxidative stress levels. Although both
metformin and
vildagliptin attenuated the depressed HRV, cardiac dysfunction, and cardiac
mitochondrial dysfunction,
vildagliptin was more effective in this prevention. Furthermore, only
vildagliptin prevented cardiac mitochondrial membrane depolarization caused by consumption of a high-fat diet. We concluded that
vildagliptin is more effective in preventing cardiac sympathovagal imbalance and cardiac dysfunction, as well as cardiac
mitochondrial dysfunction, than
metformin in rats with
insulin resistance induced by high-fat diet.