In a 3-year, longitudinal, observational study (DISCOVER), changes in health-related quality of life (HRQoL) were examined in patients with type 2 diabetes initiating a second–line glucose-lowering therapy. Findings showed HRQoL continued to be stable during follow-up but some patient features and use of sulfonylureas or insulin were linked with low or reducing HRQoL, potentially warranting the use of alternative therapies.

• In participants, mean baseline physical component summary (n = 7,428), mental component summary (n = 7,453), and Hypoglycemia Fear Survey II (n = 5,005) scores were 48.0, 45.4, and 15.4, respectively, and continued to be stable during follow-up.

• Latent class growth modelling unveiled subgroups with low or declining HRQoL.

• Older age, more comorbidities, and a lower socioeconomic status were present among patients in these subgroups when compared with other subgroups.

• The subgroup with the highest fear of hypoglycemia had the highest use of insulin and sulfonylureas.