J Diabetes 2019 Dec 29;11(12):982-992. Epub 2019 Jul 29.
Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao-Tong University, School of Medicine, Shanghai Key Laboratory for Endocrine Tumours, Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai Institute for Endocrinology, Shanghai, China.
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-naïve type 2 diabetes (T2D) patients.
Methods: In all, 282 drug-naïve T2D patients (123 normal weight [NW], with body mass index [BMI] between 19.0 and <25.0 kg/m ; 159 overweight/obese [OW/OB], with BMI ≥25.0 kg/m ) 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.