Saxagliptin alters bile acid profiles and yields metabolic benefits in drug naïve overweight or obese type 2 diabetes

BACKGROUND: The aim of the present study was to investigate the metabolic benefits of saxagliptin and its effects on serum bile acids (BAs) in normal weight and overweight/obese drug-naive type 2 diabetes (T2D) patients. METHODS: In all, 282 drug-naive T2D patients (123 normal weight [NW], with body mass index [BMI] between 19.0 and /=25.0 kg/m(2) ) were enrolled in the study and treated with saxagliptin 5 mg daily for 24 weeks. Serum BAs were assayed by liquid chromatography with tandem mass spectrometry. RESULTS: At 24 weeks, HbA1c was significantly reduced in both groups, but the HbA1c levels were lower in the OW/OB than NW group. Moreover, significant decreases were seen at 24 weeks in C-reactive protein (CRP), aspartate aminotransferase, alanine aminotransferase, waist circumference, and systolic blood pressure in the OW/OB group. Interestingly, cholic acid, glycocholic acid, glycochenodeoxycholic acid, glycodeoxycholic acid (GDCA), and glycoursodeoxycholic acid (GUDCA) were increased in both groups after treatment, whereas chenodeoxycholic acid and deoxycholic acid (DCA) were specifically increased in the OW/OB group. Increased DCA and GDCA concentrations were significantly associated with decreased HbA1c or fasting blood glucose and CRP levels, whereas increased GDCA and GUDCA concentrations were associated with decreased waist circumference in the OW/OB group during treatment. In the NW group, increased GUDCA concentrations were significantly associated with a decrease in HbA1c. CONCLUSIONS: Type 2 diabetes patients with OW/OB exhibited greater improvement in glycemic control and additional metabolic benefits after saxagliptin treatment. Saxagliptin significantly increased the BA pool, and DCA and GDCA were associated with metabolic improvements in OW/OB T2D patients.