Mitochondrial DNA copy number is a potential biomarker for treatment choice between metformin and acarbose.

Metformin is the first-line drug for type 2 diabetes (T2D) whilst acarbose is suggested as a viable alternative in Chinese patients with newly diagnosed T2D. However, little biomarkers had been established to guide the choice between these two agents. mtDNA copy number (mtDNA-CN) is a biomarker of mitochondrial function, which was associated with various metabolic outcomes. Using data from the trial of Metformin (n = 214) and AcaRbose (n = 198) in Chinese as the initial Hypoglycaemic treatment (MARCH), we examined whether mtDNA-CN was associated with response to the drugs in terms of glycaemic response and β-cell function protection response. The glycaemic response is defined as the maximum glucose reduction of HbA1c, fasting plasma glucose, or postprandial blood glucose during 48 weeks, respectively. β-cell function protection response is defined as the maximum increment of insulinogenic index (IGI) or disposition index (DI). For all three glycaemic responses, mtDNA-CN was not significantly associated with either metformin or acarbose. Importantly, for β-cell function protection response, we found the increased mtDNA-CN was significantly associated with more IGI increment (Beta: 0.84; 95% confidence interval (CI): 0.02 - 1.66) in the metformin group, but less IGI increment (Beta: -1.38; 95%CI: -2.52- -0.23) in the acarbose group. A significant interaction (P = 0.008) between mtDNA-CN and the treatment group was observed. Consistent results were also obtained when DI increment was used as a measure of β-cell function response. This study demonstrated the potential application of mtDNA-CN in guiding the treatment choice between metformin and acarbose based on beta-cell protection.