Association Between Novel Glucose-Lowering Drugs and Risk of Asthma: A Network Meta-Analysis of Cardiorenal Outcome Trials

Aims: This network meta-analysis aimed to evaluate the asthma risk associated with dipeptidyl peptidase (DPP)-4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium-glucose co-transporter (SGLT) 2 inhibitors.

Methods: Electronic databases were systematically searched up to March 2021 to include placebo-controlled cardiovascular (or cardiorenal) outcome trials that reported the asthma incidents in patients taking DPP-4 inhibitors, GLP-1RAs, or SGLT2 inhibitors. A random-effects network meta-analysis was conducted to estimate their odds ratio (ORs) and 95% confidence intervals (CIs).

Results: Nineteen trials including 218 asthma cases among 159,705 patients were included. Compared with placebo, SGLT2 inhibitors (OR, 0.59; 95% CI, 0.38-0.93) were significantly associated with a decreased risk of asthma while both DPP-4 inhibitors and GLP-1RAs did not significantly affect asthma risk. SGLT2 inhibitors were significantly associated with a lower risk of asthma than DPP-4 inhibitors (OR, 0.38; 95% CI, 0.18-0.79). There was no association between GLP-1RAs and DPP-4 inhibitors and between SGLT2 inhibitors and GLP-1RAs in risk of asthma.

Conclusions: SGLT2 inhibitors might protect against asthma while DPP-4 inhibitors and GLP-1RAs did not significantly affect the asthma incident. Given the underreporting of asthma in this study, further investigations using real-world data as well as mechanistic studies are warranted to confirm our results.