Impact of SGLT-2i on COPD Exacerbations in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis - 11/04/25

Doi : 10.1016/j.diabet.2025.101646

Prakasini Satapathy ^a,^b,^{^{†
Equally Contributed as First authors}}, Abhay M Gaidhane ^c,^{^{†
Equally Contributed as First authors}}, Nasir Vadia ^d, Soumya V Menon ^e, Kattela Chennakesavulu ^f, Rajashree Panigrahi ^g, Jayaraj Patil ^h, Ganesh Bushi ^i,^j, Mahendra Singh ^k,^l, Awakash Turkar ^m,ⁿ, Sanjit Sah ^o,^p,^q, S. Govinda Rao ^r, Khang Wen Goh ^b,^s, Muhammed Shabil ^t,^u,^⁎
^a Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
^b Faculty of Data Science and Information Technology, INTI International University, Nilai, Malaysia
^c Jawaharlal Nehru Medical College, and Global Health Academy, School of Epidemiology and Public Health. Datta Meghe Institute of Higher Education, Wardha, India
^d Marwadi University Research Center, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Marwadi University, Rajkot, 360003, Gujarat, India
^e Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
^f Department of Chemistry, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India
^g Department of Microbiology, IMS and SUM Hospital, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, Odisha, 751003, India
^h Department of Pharmacy Practice, National Institute of Pharmaceutical Education and research, Guwahati, India
ⁱ Chitkara Centre for Research and Development, Chitkara University Institute of Engineering and Technology, Chitkara University, Himachal Pradesh, 174103 India
^j School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India
^k Department of Biotechnology, Graphic Era (Deemed to be University), Clement Town, Dehradun, 248002, India
^l Graphic Era Hill University, Clement Town, Dehradun, India
^m Centre Centre for Research Impact and Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, 140401, Punjab, India
ⁿ Division of Research and Innovation, Uttaranchal University, Dehradun, India
^o Department of Paediatrics, Dr. D. Y. Patil Medical College Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed-to-be-University), Pimpri, Pune, 411018, Maharashtra, India
^p Department of Public Health Dentistry, Dr. D.Y. Patil Dental College and Hospital, Dr. D.Y. Patil Vidyapeeth (Deemed-to-be-University), Pune 411018, Maharashtra, India
^q Department of Medicine, Korea Universtiy, Seoul, South Korea
^r Department of Data Science, Gokaraju Rangaraju Institute of Engineering and Technology, Bachupally, Hyderabad, 500 090, Telangana, India
^s Faculty of Mathematics and Natural Sciences, Universitas Negeri Padang, Padang, Indonesia
^t University Center for Research and Development, Chandigarh University, Mohali, Punjab, India
^u Medical Laboratories Techniques Department, AL-Mustaqbal University, 51001 Hillah, Babil, Iraq

^⁎Corresponding author: Muhammed Shabil

Sous presse. Manuscrit accepté. Disponible en ligne depuis le Friday 11 April 2025

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.

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Keywords : COPD exacerbations, DPP-4 inhibitors, GLP-1 receptor agonists, SGLT-2 inhibitors, Sulfonylureas, Type 2 diabetes mellitus