The Potential of Antidiabetic Medications in the Prevention of Acute
                    Exacerbations of Chronic Obstructive Pulmonary Disease in Subjects with Type 2
                    Diabetes Mellitus

Theodoros Panou; Evanthia Gouveri; Fotios Drakopanagiotakis; Dimitrios Papazoglou; Paschalis Steiropoulos; Nikolaos Papanas

doi:10.1055/a-2567-7542

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2025; 133(06): 327-339
DOI: 10.1055/a-2567-7542

Mini-Review

The Potential of Antidiabetic Medications in the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease in Subjects with Type 2 Diabetes Mellitus

Theodoros Panou

¹Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Greece (Ringgold ID: RIN112220)

,

Evanthia Gouveri

¹Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Greece (Ringgold ID: RIN112220)

,

Fotios Drakopanagiotakis

²Department of Respiratory Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Greece (Ringgold ID: RIN112220)

,

Dimitrios Papazoglou

¹Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Greece (Ringgold ID: RIN112220)

,

Paschalis Steiropoulos

²Department of Respiratory Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Greece (Ringgold ID: RIN112220)

,

Nikolaos Papanas

¹Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Greece (Ringgold ID: RIN112220)

› Author Affiliations

Abstract

Type 2 diabetes mellitus (T2DM) is often recognised as a major comorbidity of chronic obstructive pulmonary disease (COPD) and is being increasingly linked with elevated risk of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Accordingly, the potential utility of antidiabetic medication, mostly in subjects suffering from both AECOPD and T2DM, has been investigated. The most widely studied medication is metformin. Although some studies showed no particular benefit, others assessed a diminished risk of AECOPD by up to 37% and reductions in hospitalisations, re-admissions, or the use of antibiotics and/or corticosteroids. The same holds true for sulfonylureas and thiazolidinediones. Conversely, dipeptidyl-peptidase 4 inhibitors (DPP-4is) were not associated with any benefit. Data on insulin use are scarce, but insulin in AECOPD management has been linked with adverse outcomes. The strongest effect has been shown with glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT-2is): the former limited severe exacerbations by 30% and the latter by 32–36%. With SGLT-2is, the incidence diminished by 46% compared with DPP-4is, while approximately three out of four emergency visits or hospitalisations were prevented. In conclusion, existing evidence suggests a benefit of antidiabetic medication in AECOPD-related outcomes, suggesting that this effect merits further investigation.

Keywords

type 2 diabetes mellitus - antidiabetic agents - chronic obstructive pulmonary disease - exacerbation

Full Text

References

References
1 Venkatesan P. GOLD COPD report: 2025 update. Lancet Respir Med 2025; 13: e7-e8
2 Rambaran K, Bhagan B, Ali A. et al. High prevalence of diabetes mellitus in a cohort of patients with chronic obstructive pulmonary disease in Trinidad, West Indies. Turk Thorac J 2019; 20: 12-17
3 Ghafil NY, Dananah FM, Hassan ES. et al. Comorbidities in patients with chronic obstructive pulmonary disease: A comprehensive study. J Med Life 2023; 16: 1013-1016
4 Krishnan JK, Martinez FJ, Altman P. et al. Multimorbidities in COPD are associated with increased exacerbations and health care resource utilization in real-world patients from a U.S. database. Chronic Obstr Pulm Dis 2024; 11: 472-481
5 Almagro P, Soler-Cataluña JJ, Huerta A. et al CLAVE Study Investigators. Impact of comorbidities in COPD clinical control criteria. The CLAVE study. BMC Pulm Med 2024; 24: 6 24.9
6 Cerezo LA, Gutiérrez GE, Llorente PC. et al. Readmission due to exacerbation of COPD: Associated factors. Lung 2018; 196: 185-193
7 Lin CS, Liu CC, Yeh CC. et al. Diabetes risks and outcomes in chronic obstructive pulmonary disease patients: Two nationwide population-based retrospective cohort studies. PLoS One 2017; 12: e0181815
8 Mao X, Liang C, Niu H. et al. Outcomes associated with comorbid diabetes among patients with COPD exacerbation: Findings from the ACURE registry. Respir Res 2021; 22: 7
9 Lin L, Shi J, Kang J. et al. Analysis of prevalence and prognosis of type 2 diabetes mellitus in patients with acute exacerbation of COPD. BMC Pulm Med 2021; 21: 7
10 Pethyabarn W, Chewae S, Dadeh AA. Factors associated with treatment failure in patients with acute exacerbation of COPD admitted to the emergency department observation unit. Emerg Med Int 2020; 2020: 8261375
11 Terzano C, Colamesta V, Unim B. et al. Chronic obstructive pulmonary disease (COPD) exacerbation: Impact of comorbidities on length and costs during hospitalization. Eur Rev Med Pharmacol Sci 2017; 21: 3680-3689
12 Parappil A, Depczynski B, Collett P. et al. Effect of comorbid diabetes on length of stay and risk of death in patients admitted with acute exacerbations of COPD. Respirology 2010; 15: 918-922
13 Koskela HO, Salonen PH, Romppanen J. et al. A history of diabetes but not hyperglycaemia during exacerbation of obstructive lung disease has impact on long-term mortality: A prospective, observational cohort study. BMJ Open 2015; 5: e006794
14 Crisafulli E, Torres A, Huerta A. et al. C-reactive protein at discharge, diabetes mellitus and≥1 hospitalization during previous year predict early readmission in patients with acute exacerbation of chronic obstructive pulmonary disease. COPD 2015; 12: 306-314
15 Belligund P, Attaway A, Lopez R. et al. Diabetes associated with higher health care utilization and poor outcomes after COPD-related hospitalizations. Am J Manag Care 2022; 28: e325-e332
16 American Diabetes Association Professional Practice Committee. 9. Pharmacologic approaches to glycemic treatment: Standards of care in diabetes-2025. Diabetes Care 2025; 48: S181-S206
17 Kahnert K, Andreas S, Kellerer C. et al. Reduced decline of lung diffusing capacity in COPD patients with diabetes and metformin treatment. Sci Rep 2022; 12: 1435
18 Karch A, Vogelmeier C, Welte T. et al. The German COPD cohort COSYCONET: Aims, methods and descriptive analysis of the study population at baseline. Respir Med 2016; 114: 27-37
19 Hitchings AW, Lai D, Jones PW. et al. Metformin in severe exacerbations of chronic obstructive pulmonary disease: A randomised controlled trial. Thorax 2016; 71: 587-593
20 Yen FS, Chen W, Wei JC. et al. Effects of metformin use on total mortality in patients with type 2 diabetes and chronic obstructive pulmonary disease: A matched-subject design. PLoS One 2018; 13: e0204859
21 Bishwakarma R, Zhang W, Lin YL. et al. Metformin use and health care utilization in patients with coexisting chronic obstructive pulmonary disease and diabetes mellitus. Int J Chron Obstruct Pulmon Dis 2018; 13: 793-800
22 Hitchings AW, Archer JR, Srivastava SA. et al. Safety of metformin in patients with chronic obstructive pulmonary disease and type 2 diabetes mellitus. COPD 2015; 12: 126-131
23 Wang MT, Lai JH, Huang YL. et al. Use of antidiabetic medications and risk of chronic obstructive pulmonary disease exacerbation requiring hospitalization: A disease risk score-matched nested case-control study. Respir Res 2020; 21: 319
24 Rinne ST, Liu CF, Feemster LC. et al. Thiazolidinediones are associated with a reduced risk of COPD exacerbations. Int J Chron Obstruct Pulmon Dis 2015; 10: 1591-1597
25 Chen KY, Wu SM, Tseng CH. et al. Combination therapies with thiazolidinediones are associated with a lower risk of acute exacerbations in new-onset COPD patients with advanced diabetic mellitus: A cohort-based case-control study. BMC Pulm Med 2021; 21: 141
26 Shanmugavel Geetha H, Teo YX, Ravichandran S. et al. Use of Sodium-glucose cotransporter 2 (SGLT 2) inhibitor is associated with reduced emergency room visits and hospitalizations in patients with Chronic obstructive pulmonary disease (COPD) and type 2 Diabetes Mellitus. Respir Med 2024; 234: 107819
27 Gupta S, Mohta A, Lauinger A. et al. The role of sodium-glucose transporter-2 inhibitors (SGLT-2i) in preventing chronic obstructive disease exacerbation in patients with diabetes and COPD: An electronic health database analysis. Heart Lung 2024; 68: 191-194
28 Gerards MC, Venema GE, Patberg KW. et al. Dapagliflozin for prednisone-induced hyperglycaemia in acute exacerbation of chronic obstructive pulmonary disease. Diabetes Obes Metab 2018; 20: 1306-1310
29 Au PCM, Tan KCB, Lam DCL. et al. Association of sodium-glucose cotransporter 2 inhibitor vs dipeptidyl peptidase-4 inhibitor use with risk of incident obstructive airway disease and exacerbation events among patients with type 2 diabetes in Hong Kong. JAMA Netw Open 2023; 6: e2251177
30 Su Y, Zhang Y, Xu J. Genetic variations in anti-diabetic drug targets and COPD risk: Evidence from mendelian randomization. BMC Pulm Med 2024; 24: 240
31 Xue H, Chen Q, Lan X. et al. Preventing CXCL12 elevation helps to reduce acute exacerbation of COPD in individuals co-existing type-2 diabetes: A bioinformatics and clinical pharmacology study. Int Immunopharmacol 2024; 132: 111894
32 Viby NE, Isidor MS, Buggeskov KB. et al. Glucagon-like peptide-1 (GLP-1) reduces mortality and improves lung function in a model of experimental obstructive lung disease in female mice. Endocrinology 2013; 154: 4503-4511
33 Foer D, Strasser ZH, Cui J. et al. Association of GLP-1 receptor agonists with chronic obstructive pulmonary disease exacerbations among patients with type 2 diabetes. Am J Respir Crit Care Med 2023; 208: 1088-1100
34 Pradhan R, Lu S, Yin H. et al. Novel antihyperglycaemic drugs and prevention of chronic obstructive pulmonary disease exacerbations among patients with type 2 diabetes: Population based cohort study. BMJ 2022; 379: e071380
35 Ray A, Paik JM, Wexler DJ. et al. Glucose-lowering medications and risk of chronic obstructive pulmonary disease exacerbations in patients with type 2 diabetes. JAMA Intern Med 2025; e247811
36 Karakasis P, Patoulias D, Fragakis N. et al Effect of newer glucose-lowering medications on chronic obstructive pulmonary disease exacerbations among individuals with type 2 diabetes. Eur J Intern Med 2025; Online ahead of print
37 Yen FS, Chang SH, Wei JC. et al. Respiratory outcomes of insulin use in patients with COPD: A nationwide population-based cohort Study. Pharmaceuticals (Basel) 2023; 16: 643
38 Chen G, Lin Q, Zhuo D. et al. Elevated blood glucose is associated with severe exacerbation of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2022; 17: 2453-2459
39 Zulkifli KK, Mohamed SFZ, Ismail AI. et al. Prevalence and associated factors of dysglycemia among patients with chronic obstructive pulmonary disease. Chron Respir Dis 2021; 18
40 Upadhyay J, Trivedi N, Lal A. Risk of future type 2 diabetes mellitus in patients developing steroid-induced hyperglycemia during hospitalization for chronic obstructive pulmonary disease exacerbation. Lung 2020; 198: 525-533
41 McGraw M, White HD, Zolfaghari K. et al. Corticosteroid dosing and glucose levels in COPD patients are not associated with increased readmissions. Chronic Obstr Pulm Dis 2021; 8: 117-123
42 Baker EH, Janaway CH, Philips BJ. et al. Hyperglycaemia is associated with poor outcomes in patients admitted to hospital with acute exacerbations of chronic obstructive pulmonary disease. Thorax 2006; 61: 284-289
43 Parappil A, Depczynski B, Collett P. et al. Effect of comorbid diabetes on length of stay and risk of death in patients admitted with acute exacerbations of COPD. Respirology 2010; 15: 918-922
44 Malhotra A, Grunstein RR, Fietze I. et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med 2024; 391: 1193-1205
45 Gouveri E, Popovic DS, Papanas N. Potential new therapeutic implications of semaglutide: New colours of the rainbow?. Diabetes Ther 2024; 15: 13-18
46 Kahnert K, Jörres RA, Lucke T. et al. Lower prevalence of osteoporosis in patients with COPD taking anti-inflammatory compounds for the treatment of diabetes: Results from COSYCONET. Int J Chron Obstruct Pulmon Dis 2021; 16: 3189-3199