The effects of linagliptin on fat content in diet-induced obese rats were compared with those of the appetite suppressant sibutramine. Female Wistar rats fed a high-fat diet (HFD) for 3 months received vehicle, linagliptin (10 mg/kg) or sibutramine (5 mg/kg) treatment orally, once daily for 6 additional weeks, while continuing the HFD. Magnetic resonance spectroscopy analysis of fat content was performed at baseline and at the end of the 6-week treatment period. Linagliptin treatment profoundly reduced hepatic fat compared with vehicle, with an effect comparable to that of sibutramine. The vehicle-corrected mean change (95% CI) from baseline in hepatic fat and intramyocellular lipid was -59.0% (-104.3%, -13.6%; p = 0.015) and -62.1% (-131.6%, 7.4%; p = 0.073), respectively, for linagliptin compared with -54.3% (-101.5%, -7.1%; p = 0.027) and -72.4% (-142.4%, -2.4%; p = 0.044), respectively, for sibutramine.