SGLT2s, GLP-1s reduce risk for COPD exacerbations

Key takeaways:

• Both SGLT2 inhibitors and GLP-1s lowered moderate or severe COPD exacerbation risk vs. DPP-4 inhibitors.
• Weight loss and SGLT2 inhibitors’ glucosuria effect may explain the findings.

Sodium-glucose cotransporter 2, or SGLT2, inhibitors and glucagon-like peptide-1 receptor agonists lowered the risk for COPD exacerbation in adults with the disease and type 2 diabetes, researchers reported.

Specifically, the treatments’ risk reductions for moderate or severe exacerbations ranged from 14% to 29% vs. dipeptidyl peptidase 4 (DPP-4) inhibitors.

The findings “were encouraging but not entirely surprising, given prior evidence on the anti-inflammatory and lung-protective effects of GLP-1s and SGLT2 inhibitors” Avik Ray, MD, MS, a postdoctoral research fellow at Brigham and Women's Hospital, and Elisabetta Patorno, MD, DrPH, an associate professor of medicine at Harvard Medical School, told Healio in a joint email.

However, “what stood out was the consistent reduction in the risk of COPD exacerbation across different analyses, reinforcing their potential role in respiratory health,” they added.

Recent research has indicated links between GLP-1 receptor agonists and COPD, with one analysis showing the medications reduced the risk for the disease.

According to Ray and colleagues, such prior studies on the effects of GLP-1 receptor agonists and SGLT2 inhibitors on varying severities of COPD exacerbations have been valuable but “were limited by small populations, exclusion of moderate exacerbations and unadjusted confounders.”

In the comparative effectiveness research study, published in JAMA Internal Medicine, the researchers analyzed data from three 1:1 propensity score-matched cohort studies, which emulated three target trials comparing adults aged 40 years or older with type 2 diabetes and COPD who initiated treatment with:

• GLP-1 receptor agonists vs. DPP-4 inhibitors;
• SGLT2 inhibitors vs. DPP-4 inhibitors; and
• SGLT2 inhibitors vs. GLP-1 receptor agonists.

There was a total of 393,847 patients across the three cohorts.

Ray and colleagues reported that the risk for moderate or severe COPD exacerbation during a median follow-up period of 145 days of treatment was lower among:

• those treated with SGLT2 inhibitors vs. DPP-4 inhibitors (9.26 vs. 11.4 events per 100 person-years; HR = 0.81; 95% CI, 0.76-0.86); and
• those treated with GLP-1 receptor agonists vs. DPP-4 inhibitors (9.89 vs. 11.49 events per 100 person-years; HR = 0.86; 95% CI, 0.81-0.91).

The risk for moderate or severe COPD exacerbation was slightly lower among those treated with SGLT2 inhibitors vs. GLP-1 receptor agonists (9.47 vs. 10 events per 100 person-years; HR = 0.94; 95% CI, 0.89-1).

The findings were consistent across subgroup and sensitivity analyses.

There were several potential explanations for the findings. For instance, GLP-1 receptor agonists and SGLT2 inhibitors produce weight loss, “which might also be associated with reduced COPD exacerbation risk, although evidence on this association remains conflicting,” the researchers wrote.

They added that SGLT2 inhibitors’ glucosuria effect “may aid carbon dioxide expulsion, benefiting patients with COPD,” while the drugs’ link to fluid reduction could additionally help those with COPD and coexisting congestive heart failure “by alleviating fluid overload.”

Ray and colleagues said they could not rule out residual confounding, while there was a lack of follow-up data on BMI and HbA1c levels, ultimately preventing them from seeing how changes in these measures mediated the reduced risk for exacerbations.

The data indicate that primary care providers “may consider prescribing SGLT2 inhibitors or GLP-1s over DPP-4 inhibitors for patients with type 2 diabetes and COPD, as these medications may help reduce the risk of COPD exacerbations while also managing diabetes effectively,” Ray and Patorno told Healio.

The two researchers added the findings also support the idea “that the benefits of certain diabetes medications go beyond glucose control.”

“More studies are needed to explore the potential role of diabetes medications in the setting of patients with multiple health concerns,” they said.