Diabetes is associated with increased fracture risk in human bone, especially in the elderly population. In the present study, we investigate how simulated advanced glycation end-products (AGEs) and materials heterogeneity affect crack growth trajectory in human cortical bone. We used a phase field fracture framework on 2D models of cortical microstructure created from human tibias to analyze crack propagation. The increased AGEs level results in a higher rate of crack formation. The simulations also indicate that the mismatch between the fracture properties (e.g., critical energy release rate) of osteons and interstitial tissue can alter the post-yielding behavior. The results show that if the critical energy release rate of cement lines is lower than that of osteons and the surrounding interstitial matrix, cracks can be arrested by cement lines. Additionally, activation of toughening mechanisms such as crack merging and branching depends on bone microstructural morphology (i.e., osteons geometrical parameters, canals, and lacunae porosities). In conclusion, the present findings suggest that materials heterogeneity of microstructural features and the crack-microstructure interactions can play important roles in bone fragility.