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Association of the Use of Novel Antihyperglycaemic Drugs With Prevention of COPD Exacerbations Among Patients With Type 2 Diabetes
TAKE-HOME MESSAGE
- This population-based cohort study evaluated data from individuals who were new users of glucagon-like peptide 1 (GLP-1) receptor agonists, sodium–glucose co-transporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase 4 (DPP-4) inhibitors, or sulfonylureas with a history of diabetes and chronic obstructive pulmonary disease (COPD) to determine whether the use of these medications decreases the risk of COPD exacerbations in these individuals. Compared with sulfonylureas, GLP-1 receptor agonists were associated with a decreased risk of moderate and severe COPD exacerbation, SGLT-2 inhibitors were associated with a decreased risk of severe COPD exacerbation, and DPP-4 inhibitors did not show a consistent association. There are multiple possibilities for the reasons of this decreased risk, including the anti-inflammatory properties of GLP-1 receptor agonists and the decreased carbon dioxide production associated with SGLT-2 inhibitors.
- As the use of GLP-1 receptor agonists and SGLT-2 inhibitors is becoming common, there is increasing information about the benefits of these medications in many realms. This study suggests that these classes of medications can also decrease the risk of COPD exacerbation in individuals with diabetes using these medications.
abstract
This abstract is available on the publisher's site.
Access this abstract nowOBJECTIVE
To determine whether the use of glucagon-like peptide 1 (GLP-1) receptor agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors, and sodium-glucose co-transporter-2 (SGLT-2) inhibitors, separately, is associated with a decreased risk of exacerbations of chronic obstructive pulmonary disease among patients with chronic obstructive pulmonary disease and type 2 diabetes.
DESIGN
Population based cohort study using an active comparator, new user design.
SETTING
The United Kingdom Clinical Practice Research Datalink linked with the Hospital Episode Statistics Admitted Patient Care and Office for National Statistics databases.
PARTICIPANTS
Three active comparator, new user cohorts of patients starting the study drugs (GLP-1 receptor agonists, DPP-4 inhibitors, or SGLT-2 inhibitors) or sulfonylureas with a history of chronic obstructive pulmonary disease. The first cohort included 1252 patients starting GLP-1 receptor agonists and 14 259 starting sulfonylureas, the second cohort included 8731 patients starting DPP-4 inhibitors and 18 204 starting sulfonylureas, and the third cohort included 2956 patients starting SGLT-2 inhibitors and 10 841 starting sulfonylureas.
MAIN OUTCOME MEASURES
Cox proportional hazards models with propensity score fine stratification weighting were fitted to estimate hazard ratios and 95% confidence intervals of severe exacerbation of chronic obstructive pulmonary disease (defined as hospital admission for chronic obstructive pulmonary disease), separately for GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors. Whether these drugs were associated with a decreased risk of moderate exacerbation (defined as a co-prescription of an oral corticosteroid and an antibiotic along with an outpatient diagnosis of acute chronic obstructive pulmonary disease exacerbation on the same day) was also assessed.
RESULTS
Compared with sulfonylureas, GLP-1 receptor agonists were associated with a 30% decreased risk of severe exacerbation (3.5 v 5.0 events per 100 person years; hazard ratio 0.70, 95% confidence interval 0.49 to 0.99) and moderate exacerbation (0.63, 0.43 to 0.94). DPP-4 inhibitors were associated with a modestly decreased incidence of severe exacerbation (4.6 v. 5.1 events per 100 person years; hazard ratio 0.91, 0.82 to 1.02) and moderate exacerbation (0.93, 0.82 to 1.07), with confidence intervals including the null value. Finally, SGLT-2 inhibitors were associated with a 38% decreased risk of severe exacerbation (2.4 v 3.9 events per 100 person years; hazard ratio 0.62, 0.48 to 0.81) but not moderate exacerbation (1.02, 0.83 to 1.27).
CONCLUSIONS
In this population based study, GLP-1 receptor agonists and SGLT-2 inhibitors were associated with a reduced risk of severe exacerbations compared with sulfonylureas in patients with chronic obstructive pulmonary disease and type 2 diabetes. DPP-4 inhibitors were not clearly associated with a decreased risk of chronic obstructive pulmonary disease exacerbations.
Additional Info
Disclosure statements are available on the authors' profiles:
Novel antihyperglycaemic drugs and prevention of chronic obstructive pulmonary disease exacerbations among patients with type 2 diabetes: population based cohort study
BMJ 2022 Nov 01;379(xx)e071380, R Pradhan, S Lu, H Yin, OHY Yu, P Ernst, S Suissa, L AzoulayFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
With their UK-based cohort study on novel antihyperglycemic drugs and prevention of chronic obstructive pulmonary disease (COPD) exacerbations, Pradhan et al bring methodologic rigor and clarity to a growing body of literature at the intersection of obstructive respiratory disease and type 2 diabetes (T2D) medications. Across three separate active comparator new-user cohorts of patients with COPD and T2D, GLP-1 receptor agonists (GLP-1RA) and SGLT2 inhibitors (SGLT2i), but not DPP-4 inhibitors, were associated with lower risk of severe exacerbations compared with sulfonylurea treatment. GLP-1RA were additionally associated with decreased risk of moderate exacerbations and lower moderate exacerbation rates, which was not the case for SGLT2i users.
From a mechanistic perspective, the strongest evidence for novel anti-hyperglycemic drugs in the realm of obstructive respiratory disease is for GLP-1RA and asthma, supported by several recent observational human studies. Indeed, as the authors note, the lower severe COPD exacerbation risk associated with GLP-1RA was among patients who also had an asthma diagnosis history, but not among COPD patients who lacked an asthma diagnosis. Across the treatment cohorts, an asthma history was surprisingly present in more than half of the COPD study population. Pradhan et al directly address gaps in prior studies to bolster the case for GLP-1RA and SGLT2i benefits in COPD. In doing so, they also draw contrast to a recent randomized controlled trial of liraglutide in patients with COPD and obesity, where the primary outcome of FEV1 improvement was not met. Change in pulmonary function was not an outcome in Pradhan et al, highlighting clinical questions about what can be reasonably expected from these drugs in the context of chronic respiratory disease.
More broadly, there is now a steady drumbeat of publications in Endocrinology and Pulmonary journals probing the interrelationship of insulin resistance, obesity, and obstructive respiratory disease. These studies, in tandem with the shift to a holistic, person-centered T2D management approach that considers patient comorbidities, compel exciting questions about care for our patients with T2D and comorbid asthma or COPD. But currently, respiratory disease is not a featured comorbidity in T2D treatment algorithms, and T2D is lacking from consideration in leading asthma guidelines. Pradhan et al’s study may signal a coming paradigm shift for clinicians to consider respiratory comorbidities in the context of T2D care. In the interim, prospective research is needed to assess the therapeutic value of these drugs in patients with COPD and asthma with and without T2D.