Among patients with type 2 diabetes (T2D) and chronic lower respiratory disease (CLRD), treatment with glucagon-like peptide 1 receptor agonists (GLP-1RA) was associated with fewer CLRD exacerbations compared with dipeptidyl peptidase 4 inhibitors (DPP-4I), according to research published in Diabetes Care.

Previous studies have shown that GLP-1RAs demonstrate a protective effect by attenuating bronchial hyperresponsiveness. In this study, the investigators aimed to evaluate the association between GLP-1RA use and CLRD exacerbations in patients with T2D and CLRD.

The new-user active-comparator analysis consisted of GLP-1RA (n=4150) and DPP-4I (n=12,540) users from the IBM MarketScan Commercial Claims Database from 2005 to 2017. Patients were included in the study if they had at least 1 inpatient or 2 outpatient encounters with T2DM and CLRD, and were started on a GLP-1RA (exenatide, liraglutide, dulaglutide, or albiglutide) or DPP-4I (saxagliptin, sitagliptin, linagliptin, or alogliptin) as an add-on therapy to their antidiabetic regimen. Patients were evaluated and followed for 1 year.

The primary endpoint was time to first hospital admission for CLRD, defined as hospital admission for either a primary or secondary diagnosis of CLRD. The authors also looked at the number of CLRD exacerbations that required an emergency room (ER) visit, inpatient care, or systemic corticosteroid use as a secondary outcome.

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Baseline characteristics, CLRD medication use (eg, controllers, rescue medications), and healthcare services use were fairly similar in both groups. More females were included in the study, with 65% in the GLP-1RA group and 55% in the DPP-4I group. Obesity was significantly higher in GLP-1RA users (34%) compared with DPP-4I users (21%).  

A total of 174 new CLRD hospitalizations were identified in the study. The investigators found that GLP-1RA use was associated with a lower incidence of CLRD hospitalization with a rate of 11 per 1000 person-years (95% CI, 7.3-16.6) compared with a rate of 20.6 per 1000 person-years (95% CI, 17.6-24.2) in DPP-4I users. The adjusted incidence rate of first CLRD admission during follow-up was 10.7 and 20.3 per 1000 person-years for GLP-1RA and DPP-4I users, respectively (adjusted hazard ratio [HR] 0.52; 95% CI, 0.32-0.85).

For the secondary endpoint, a total of 650 exacerbations requiring ER or inpatient care or oral steroid use were identified. GLP-1RA use was associated with fewer exacerbations (~13 less per 1000 person-years) compared with DPP-4I users, with an adjusted incidence rate ratio of 0.70 (95% CI, 0.56-0.86).

The investigators concluded that patients with T2DM and CLRD who initiated GLP-1RA had a lower incidence rate of CLRD hospitalizations and exacerbations compared with those who initiated DPP-4I. “Considering both plausible mechanistic pathways and this real-world evidence, potential beneficial effects of GLP-1RA should be considered in selection of antidiabetes treatment regimen,” the authors stated.


Albogami Y, Cusi K, Daniels MJ, Wei YJ, Winterstein AG. Glucagon-like peptide 1 receptor agonists and chronic lower respiratory disease exacerbations among patients with type 2 diabetes. [published online April 19, 2021]. Diabetes Care. doi: 10.2337/DC20-1794