Effect of Acarbose and Vildagliptin on Plasma Trimethylamine N-oxide Levels in Patients with Type 2 Diabetes Mellitus: A 6-month, Two-arm Randomized Controlled Trial

Xinhui Yang ¹ Xiuying Zhang ² Chen Sun ¹ Cuiling Zhao ¹ Xiangshuang Kong ¹ Zhun Shi ³ Huahui Ren ³ Huanzi Zhong ³ Mingming Zhao ^4* Linong Ji ^2* Yufeng Li ^5*

• ¹ Department of Endocrinology, Beijing Friendship Hospital Pinggu Campus, Capital Medical University, Beijing, China
• ² Department of Endocrinology and Metabolism, Peking University People’s Hospital, Peking University Diabetes Centre, Beijing, China
• ³ BGI Genomics, Shenzhen, China
• ⁴ Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China
• ⁵ Beijing Friendship Hospital, Capital Medical University, Beijing, China

Aim: We aimed to assess the effects of acarbose and vildagliptin on levels of plasma trimethylamine N-oxide (TMAO) and its metabolic precursor in overweight and obese patients with type 2 diabetes mellitus and ascertain the correlation between TMAO and characteristics of diabetes. Methods: This study employed a randomized, controlled, open interventional design and recruited 100 participants who were overweight/obese and newly diagnosed with type 2 diabetes at Pinggu Hospital, Beijing Friendship Hospital, Capital Medical University, between December 2016 and December 2017. Using the sealed envelope method, participants were randomly allocated (1:1) to either the acarbose group (n = 50) or the vildagliptin group (n = 50). Participants received 6 months of treatment with oral glucose-lowering medications, acarbose, or vildagliptin. Anthropometric measurements, including height, weight, waist and hip circumferences, and blood pressure, were recorded at baseline and 3 and 6 months after the intervention. Blood samples were obtained to assess blood glucose, insulin, gut hormones, TMAO, and metabolic precursors. Data analysis focused on intragroup and intergroup variations. Results: Baseline characteristics, including weight, BMI, waist and hip circumferences, blood glucose, and gut hormone levels, were comparable between the acarbose and vildagliptin groups (all p>0.05). Intragroup analysis indicated a significant decrease in TMAO levels at 6 months compared with baseline (adjusted p<0.05). L-carnitine and γ-butyrobetaine levels significantly increased at 6 months (all adjusted p<0.05), whereas betaine and choline levels remained non-significant throughout the intervention. Intergroup analysis revealed significantly lower TMAO levels in the acarbose group at 6 months (p<0.05), without significant intergroup differences in L-carnitine, γ-butyrobetaine, choline, or betaine levels (all p>0.05). In the acarbose group, positive correlations were observed between changes in TMAO and BMI, waist circumference, postprandial glucose, fasting insulin, fasting C-peptide, and HOMA-IR from baseline to 6 months (p<0.05). Conclusions: Both acarbose and vildagliptin treatments significantly reduced TMAO levels in newly diagnosed T2DM patients, with a more pronounced reduction observed in the acarbose group. Furthermore, the decline in TMAO levels correlated significantly with improvements in insulin resistance parameters.