Mitochondrial DNA Copy Number Is a Potential Biomarker for Treatment Choice Between Metformin and Acarbose

Abstract

Metformin is the first‐line drug for type 2 diabetes (T2D) while acarbose is suggested as a viable alternative in Chinese patients with newly diagnosed T2D. However, few biomarkers have been established to guide the choice between these two agents. Mitochondrial DNA (mtDNA) copy number (mtDNA‐CN) is a biomarker of mitochondrial function, which is associated with various metabolic outcomes. Using data from the trial of Metformin and Acarbose in Chinese as the Initial Hypoglycaemic Treatment (MARCH) (metformin n = 214; acarbose n = 198), we examined whether mtDNA‐CN was associated with response to the drugs in terms of glycemic response and β‐cell function protection response. The glycemic response is defined as the maximum glucose reduction of glycated hemoglobin A1c, fasting plasma glucose, or postprandial blood glucose during 48 weeks. β‐cell function protection response is defined as the maximum increment of insulinogenic index (IGI) or disposition index (DI). For all three glycemic 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 to 1.66) in the metformin group, but less IGI increment (beta: −1.38; 95% CI, −2.52 to −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 β‐cell protection.