Muhammed Shabil, Jayaraj Patil, Prakasini Satapathy, Abhay M Gaidhane, Kattela Chennakesavulu, Nasir Vadia, Soumya V Menon, Rajashree Panigrahi, Ganesh Bushi, Mahendra Singh, Sanjit Sah, Awakash Turkar, Khang Wen Goh, S. Govinda Rao, Edward Mawejje
Background: Chronic obstructive pulmonary disease (COPD) and Type 2 diabetes mellitus (T2DM) frequently coexist, amplifying morbidity, mortality, and healthcare costs. COPD exacerbations are more frequent and severe in T2DM patients, necessitating therapies addressing both conditions. This systematic review and meta-analysis evaluates the impact of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on COPD exacerbations in T2DM patients. Methods: Following PRISMA guidelines, we searched PubMed, Embase, and Web of Science until March 2025 for studies assessing SGLT-2i effects on COPD exacerbations in T2DM. Eligible studies included adults with T2DM-COPD overlap, reporting exacerbation outcomes. A random-effects meta-analysis and Bayesian hierarchical models were employed, with sensitivity and subgroup analyses. Results: Seven studies (449,530 participants) were included. SGLT-2i use reduced COPD exacerbation risk by 39% (pooled HR: 0.609, 95% CI: 0.431–0.858), with Bayesian analysis supporting a 31% reduction (HR: 0.64, 95% CrI: 0.40–0.88). Subgroup analyses showed superior efficacy vs DPP-4 inhibitors (HR: 0.618, 95% CI: 0.462–0.827) and sulfonylureas (HR: 0.620, 95% CI: 0.526–0.731), and modest benefit over GLP-1RAs (HR: 0.940, 95% CI: 0.890–0.992). Severe exacerbation reduction was non-significant (HR: 0.676, 95% CI: 0.340–1.344). Heterogeneity was high (I2 ≥ 97.9%), but sensitivity analyses confirmed robustness. Conclusions: SGLT-2 inhibitors significantly reduce COPD exacerbations in T2DM patients, offering dual cardiometabolic and respiratory benefits. Their superiority over other antidiabetic agents supports prioritization in high-risk T2DM-COPD populations. Further trials are needed to validate effects on severe exacerbations and elucidate mechanisms. © 2025 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.
Department of Pharmacy Practice, Faculty of Pharmacy, MS Ramaiah University of Applied Sciences, Bangalore, India; Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research, Guwahati, India; Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Tamil Nadu, Chennai, India; Faculty of Data Science and Information Technology, INTI International University, Nilai, Malaysia; Jawaharlal Nehru Medical College, Global Health Academy, School of Epidemiology and Public Health, Datta Meghe Institute of Higher Education, Wardha, India; Department of Chemistry, Sathyabama Institute of Science and Technology, Tamil Nadu, Chennai, India; Marwadi University Research Center, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Marwadi University, Gujarat, Rajkot, India; Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Karnataka, Bangalore, India; Department of Microbiology, IMS and SUM Hospital, Siksha ‘O’ Anusandhan (Deemed to be University), Odisha, Bhubaneswar, India; Department of Biotechnology, Graphic Era (Deemed to be University), Dehradun, India; Graphic Era Hill University, Dehradun, India; SR Sanjeevani Hospital, Kalyanpur, Siraha, Nepal; Department of Paediatrics, Dr. D. Y. Patil Medical College Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed-to-be-University), Maharashtra, Pune, India; Department of Medicine, Korea Universtiy, Seoul, South Korea; Centre for Research Impact and Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Punjab, Rajpura, India; Division of Research and Innovation, Uttaranchal University, Dehradun, India; Faculty of Mathematics and Natural Sciences, Universitas Negeri Padang, Padang, Indonesia; Department of Data Science, Gokaraju Rangaraju Institute of Engineering and Technology, Telangana, Hyderabad, India; School of Public Health, Makerere University College of Health Sciences, Kampala, Uganda
