Nicolucci A, Chen H, Cid-Ruzafa J, et al. - Researchers conducted the study for examining factors correlated with health-related quality of life (HRQoL) in patients with type 2 diabetes mellitus (T2D) at the initiation of second-line glucose-lowering therapy. DISCOVER is a 3-year, prospective observational study of patients with T2D starting second-line glucose-lowering therapy, carried out in 38 countries. The physical and mental component summary scores of the 36-Item Short Form Health Survey version 2 (SF-36v2) in 31 countries (n = 8,309) and the Hypoglycaemia Fear Survey-II (HFS-II) in 23 countries (n = 6,516) were used to assess HRQoL at baseline. Using multivariable hierarchical regression models, factors associated with differences in HRQoL were assessed. Female gender, a history of macrovascular complications, and first-line treatment with oral combinations (vs metformin monotherapy) were all associated with significantly lower SF-36v2 scores. Several patient-, disease-, and treatment-related characteristics were found to be related to HRQoL, indicating that a multifactorial approach is required to maintain HRQoL in T2D patients.