Coronary computed tomography angiography (CTA) allows anatomical visualization of coronary arteries and plaques while positron emission tomography (PET) myocardial perfusion imaging (MPI) provides detailed information on functional consequences of coronary artery plaques. Anatomical and functional imaging can complement each other in the assessment of coronary artery disease (CAD). Diabetes is a risk factor for development of CAD and is associated with adverse clinical outcomes. In turn, lipid-lowering medication (LLM) has a key role in prevention of CAD development and progression and reducing the risk for adverse clinical events. We found that coronary CTA with selective downstream use of PET MPI for functional evaluation enables long-term risk stratification both in symptomatic patients with and without diabetes with suspected CAD. However, diabetes was associated with more advanced CAD and worse long-term clinical outcomes independent of myocardial perfusion results, whereas normal myocardial perfusion was associated with favorable prognosis in patients without diabetes. Quantified coronary atherosclerotic burden was an important predictor of long-term outcomes both in patients with and without diabetes. Moreover, we found that coronary CTA and PET perfusion findings guide subsequent use of LLM, which is associated with outcome benefit in patients with obstructive or ischemic CAD. Yet adherence to LLM declines over time. Multimodality imaging enables comprehensive assessment of CAD severity, helps guide risk stratification, and supports medication adherence in high-risk patients.