Abstract
AIMS: Dapagliflozin and sitagliptin exhibit variable efficacy in managing type 2 diabetes mellitus (T2DM), with outcomes influenced by factors like body mass index (BMI). However, biochemical determinants of treatment response remain poorly defined. This study aimed to determine whether baseline alanine aminotransferase (ALT) levels can independently predict differential responses to these drugs. MATERIALS AND METHODS: This post hoc analysis of the Dapagliflozin Versus Sitagliptin for Type 2 Diabetes-Cardiovascular Risk (DIVERSITY-CVR) study, a randomized, open-label trial in Japan, included 340 patients with T2DM on metformin monotherapy or no treatment. Analysis of variance and regression analyses were conducted, adjusting for allocation factors (glycated haemoglobin [HbA1c] ≥/< 8.5%, BMI ≥/< 27 kg/m(2), metformin >/≤ 0.5 g/day). Three models (M1-M3) included baseline HbA1c, BMI and/or allocation adjustment factors. Co-primary endpoints were HbA1c and time in range. RESULTS: Baseline ALT levels were significantly associated with changes in HbA1c and time in range at 24 weeks. Patients with lower ALT showed better response to sitagliptin, while those with higher ALT exhibited enhanced efficacy with dapagliflozin across all models (p < 0.05). Regression analysis revealed significant interactions between ALT, BMI and HbA1c (p = 0.02, 0.03). A significant correlation between baseline ALT and HbA1c change was observed in the total cohort (p = 0.03) and sitagliptin group (p < 0.01). CONCLUSIONS: Baseline ALT is a potential predictor of differential efficacy between dapagliflozin and sitagliptin in T2DM, independent of BMI. Lower ALT correlated with enhanced sitagliptin efficacy, whereas higher ALT favoured dapagliflozin for glycaemic control. TRIAL REGISTRATION: The DIVERSITY-CVR study was registered with the University Hospital Medical Information Network Clinical Trial Registry (UMIN000028014).