Impact of SGLT-2i on COPD exacerbations in patients with type 2 diabetes mellitus: A systematic review and meta-analysis

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Prakasini Satapathy, Abhay M Gaidhane, Nasir Vadia, Soumya V Menon, Kattela Chennakesavulu, Rajashree Panigrahi, Jayaraj Patil, Ganesh Bushi, Mahendra Singh, Awakash Turkar, Sanjit Sah, S. Govinda Rao, Khang Wen Goh, Muhammed Shabil

2025 Diabetes and Metabolism Vol. 51 Issue 4 Review Cited by 6 Quartile

Abstract

Background: Chronic Obstructive Pulmonary Disease (COPD) and Type 2 Diabetes Mellitus (T2DM) often coexist, leading to compounded morbidity, mortality, and healthcare burden. COPD exacerbations significantly impact patients with T2DM, with increased frequency and severity. Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have demonstrated promising benefits in managing both glycemic control and respiratory health. This systematic review and meta-analysis aim to assess the impact of SGLT-2 inhibitors on COPD exacerbations in T2DM patients. Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines, evaluating studies published until March 2025. A broad search strategy across PubMed, Embase, and Web of Science identified relevant studies comparing SGLT-2 inhibitors with other antidiabetic agents. Studies meeting predefined eligibility criteria, including those providing quantitative data on COPD exacerbation frequency and hospitalization rates, were included in the analysis. Results: Eight studies involving 4,64,542 participants were included. The pooled hazard ratio (HR) for the impact of SGLT-2 inhibitors on COPD exacerbations was 0.646 (95 % CI: 0.470–0.889), demonstrating a 35 % decrease in exacerbations compared to other antidiabetic agents. SGLT-2 inhibitors demonstrated superior efficacy over DPP-4 inhibitors (HR: 0.618, 95 % CI: 0.462–0.827) and sulfonylureas (HR: 0.620, 95 % CI: 0.526–0.731). However, the reduction in severe exacerbations was not statistically significant (HR: 0.715, 95 % CI: 0.403–1.269). Subgroup analysis indicated that SGLT-2 inhibitors had a modest but significant advantage over GLP-1 receptor agonists (HR: 0.940, 95 % CI: 0.890–0.993). Conclusions: SGLT-2 inhibitors significantly reduce COPD exacerbations in T2DM patients, offering dual benefits in managing both glycemic control and respiratory health. These findings support the integration of SGLT-2 inhibitors into treatment regimens for T2DM-COPD overlap. Further randomized controlled trials and long-term studies are needed to confirm the lasting efficacy and explore the underlying mechanisms. © 2025

Affiliations

Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; Faculty of Data Science and Information Technology, INTI International University, Nilai, Malaysia; Jawaharlal Nehru Medical College, and Global Health Academy, School of Epidemiology and Public Health. Datta Meghe Institute of Higher Education, Wardha, India; Marwadi University Research Center, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Marwadi University, Gujarat, Rajkot, 360003, India; Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Karnataka, Bangalore, India; Department of Chemistry, Sathyabama Institute of Science and Technology, Tamil Nadu, Chennai, India; Department of Microbiology, IMS and SUM Hospital, Siksha 'O' Anusandhan (Deemed to be University), Odisha, Bhubaneswar, 751003, India; Department of Pharmacy Practice, National Institute of Pharmaceutical Education and research, Guwahati, India; Chitkara Centre for Research and Development, Chitkara University Institute of Engineering and Technology, Chitkara University, Himachal Pradesh, 174103, India; School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India; Department of Biotechnology, Graphic Era (Deemed to be University), Dehradun, Clement Town, 248002, India; Graphic Era Hill University, Dehradun, Clement Town, India; Centre Centre for Research Impact and Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Punjab, Rajpura, 140401, India; Division of Research and Innovation, Uttaranchal University, Dehradun, India; Department of Paediatrics, Dr. D. Y. Patil Medical College Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed-to-be-University), Pimpri, Maharashtra, Pune, 411018, India; Department of Public Health Dentistry, Dr. D.Y. Patil Dental College and Hospital, Dr. D.Y. Patil Vidyapeeth (Deemed-to-be-University), Maharashtra, Pune, 411018, India; Department of Medicine, Korea Universtiy, Seoul, South Korea; Department of Data Science, Gokaraju Rangaraju Institute of Engineering and Technology, Bachupally, Telangana, Hyderabad, 500 090, India; Faculty of Mathematics and Natural Sciences, Universitas Negeri Padang, Padang, Indonesia; University Center for Research and Development, Chandigarh University, Punjab, Mohali, India; Medical Laboratories Techniques Department, AL-Mustaqbal University, Babil, Hillah, 51001, Iraq