BACKGROUND: In statins-treated diabetic mellitus (DM) patients, longitudinal coronary CTA (CCTA) evidence is scarce regarding the relationship between coronary Agatston artery calcification scores (CACs) and coronary plaque progression. This study was designed to investigate whether the association between CACs progression and compositional plaque volumes (PVs) progression differed between follow-up low-density lipoprotein cholesterol (LDL-C) controlled and uncontrolled groups in statins-treated DM patients. METHODS: From January 2015 to June 2021, 208 patients who submitted serial clinically indicated CCTAs in our hospital were included in this study. Participants were further subdivided into LDL-C controlled (n = 75) and LDL-C uncontrolled (n = 133) groups according to whether the LDL-C reached the treatment goals at follow-up. Baseline and follow-up CCTA image datasets were quantified analysis at per-patient and per-plaque levels. The annual change of total PV (TPV), calcific PV(CPV), non-calcific PV (NCPV), low-density non-calcific PV (LD-NCPV), and CACs were assessed and further compared according to follow-up LDL-C status. The effect of CACs progression on the annual change of componential PVs was evaluated according to follow-up LDL-C status at both per-patient and per-plaque levels. RESULTS: The annual change of CACs was positively associated with the annual change of TPV (β = 0.43 and 0.61, both p < 0.001), CPV (β = 0.23 and β = 0.19, p < 0.001 and p = 0.004, respectively), NCPV (β = 0.20 and β = 0.42, p < 0.001 and p = 0.006, respectively), and LD-NCPV (β = 0.08 and 0.13, p < 0.001 and p = 0.001, respectively) both on per-patients and per-plaque levels. LDL-C status had no effect on the annual change of TPV, CPV, NCPV, and LD-NCPV (all p > 0.05). After adjusting for confounding factors, on the per-patient level, the increase in CACs was independently associated with annual change of TPV (β = 0.650 and 0.378, respectively, both p < 0.001), CPV (β = 0.169 and 0.232, respectively, p = 0.007 and p < 0.001), NCPV (β = 0.469 and 0.144, respectively, both p = 0.001), and LD-NCPV (β = 0.082 and 0.086, respectively, p = 0.004 and p = 0.006) in LDL-C controlled and LDL-C uncontrolled group. On the per-plaque level, the increase in CACs was independently associated with the annual change of NCPV and LD-NCPV in LDL-C uncontrolled patient (β = 0.188 and 0.106, p < 0.001), but not in LDL-C controlled group (β = 0.268 and 0.056, p = 0.085 and 0.08). CONCLUSIONS: The increase of CACs in statins-treated DM patients indicates the progression of compositional PVs. From a per-plaque perspective, there might be increased instability of individual plaques concomitant with CACs increase in LDL-C uncontrolled patients.