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Aims: To describe health-related quality of life (HRQoL) and identify associated factors in patients with type 2 diabetes mellitus (T2DM) treated with oral glucose-lowering drugs (OGLDs)., Methods: This retrospective, cross-sectional analysis included adults with T2DM from 11 Asian countries/regions prospectively enrolled in the Joint Asian Diabetes Evaluation (JADE) Register (2007-2019) with available EuroQol-5D (EQ-5D-3L) data., Results: Of 47,895 included patients, 42,813 were treated with OGLDs + lifestyle modifications (LSM) and 5,082 with LSM only. Among those treated with OGLDs, 60% received sulphonylureas (SUs), of whom 47% received gliclazide. The OGLD + LSM group had a lower mean EQ-5D-3L index score than the LSM-only group (p < 0.001). The most affected EQ-5D-3L dimensions in OGLD + LSM-treated patients were pain/discomfort (26.2%) and anxiety/depression (22.6%). On multivariate analysis, good HRQoL was positively associated with male sex, education level, balanced diet and regular exercise, and negatively with complications/comorbidities, self-reported hypoglycaemia, smoking, HbA1c, age, body mass index and disease duration. Patients receiving gliclazide vs non-gliclazide SUs had lower HbA1c and better HRQoL in all dimensions (p < 0.001)., Conclusions: Demographic, physical and psychosocial-behavioural factors were associated with HRQoL in patients with T2DM. Our real-world data add to previous evidence that gliclazide is an effective OGLD, with most treated patients reporting good HRQoL. A plain language summary of this manuscript is available here., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Lee-Ling Lim reports receiving grants and/or honoraria for consultancy or giving lectures from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Novo Nordisk, Roche, Sanofi, Servier, Viatris Pharmaceutical and Zuellig Pharma. Eric S.H. Lau reports no conflicts of interest. Siew Pheng Chan reports receiving grants and/or honoraria for consultancy or giving lectures from Abbott, AstraZeneca, Boehringer Ingelheim, Merck Serono, Merck Sharp & Dohme, Novo Nordisk, Sanofi, Servier and Zuellig Pharma. Linong Ji reports receiving consulting and lecture fees from Eli Lilly, Novo Nordisk, Merck, Sanofi-Aventis, MSD, Servier and Boehringer Ingelheim. Soo Lim has been a member of advisory boards or has consulted for Merck, Sharp & Dohme, NovoNordisk and Servier, has received grant support from AstraZeneca, Merck, Sharp & Dohme and Astellas, and has served on the speakers' bureau of AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., Merck, Sharp & Dohme, CKD Pharmaceutical and NovoNordisk. Sirinart Sirinvaravong reports receiving honoraria for giving lectures from Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi, Servier and Zuellig Pharma. A. G. Unnikrishnan reports receiving grants via affiliated institutions, advisory board and speaker contracts from AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Sanofi, Serdia, Servier, Novo Nordisk and Roche. Andrea O.Y. Luk reports receiving grants and/or honoraria for consultancy or giving lectures from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Merck Sharp & Dohme, Lee's Pharmaceutical, Roche and Sanofi. The proceeds have been donated to CUHK, the ADA and other charity organizations to support diabetes research and education. Viviana Cortese and Alexandra Durocher are employees of Servier. Juliana C.N. Chan reports receiving research grants through her affiliated institutions, honoraria and speakers' fees from Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Celltrion, Hua Medicine, Powder Pharmaceuticals, Lilly, Merck Sharp & Dohme, Merck Serono, Pfizer, Sanofi, Servier, Viatris Pharmaceutical and Zuellig Pharma, holds patents of genetic markers for predicting diabetes and its complications, and is a cofounder of a biotechnology start-up company, GemVCare, with partial support from the Hong Kong Government Innovation and Technology Commission for providing precision diabetes care and Chief Executive Officer of Asia Diabetes Foundation on a pro bono basis.]., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)