Using inhaled corticosteroids for 24-plus months ups diabetes, osteoporosis risk in COPD
Key takeaways:
- Inhaled corticosteroids are often used outside of the recommended indications in COPD.
- Researchers revealed a link between long-term use and several risks for new diagnoses.
Adults with COPD who used inhaled corticosteroids for more than 24 months faced higher risks for diabetes, osteoporosis, pneumonia, cataracts and fractures than those with less than 4 months’ use, according to study data.
These findings were published in Annals of Family Medicine.
“ICS therapy is indicated only for those who have COPD and asthma or asthma-like features of their COPD, who have elevated blood eosinophil counts and those with frequent moderate to severe exacerbations,” Barbara P. Yawn, MD, MSc, FAAFP, adjunct professor in the department of family and community health at University of Minnesota, told Healio. These indications do not describe most patients with COPD, she said.
“Our findings highlight the need to consider the risk of beginning ICS therapy for COPD — is it indicated?” Yawn continued. “Once ICS therapy is started, it is rarely stopped, and with only 24-plus months of use, 29.4% of individuals will have one or more of the adverse outcomes we studied — new onset diabetes, cataracts, pneumonia, osteoporosis and nontraumatic fractures.”
Using electronic health record data, Yawn, Wilson D. Pace, MD, chief medical and technology officer at DARTNet Institute and professor of family medicine at University of Colorado Health Sciences Center, and colleagues evaluated two sets of adults aged at least 45 years with COPD — 318,385 with a COPD diagnosis at any time (prevalent cohort) and 209,062 with a new COPD diagnosis (inception cohort) — to determine how long-term ICS use of more than 24 months impacts the risk for a new diagnosis of type 2 diabetes, cataracts, pneumonia, osteoporosis or nontraumatic fracture vs. short-term ICS use of less than 4 months.
Researchers also investigated how the risk for recurrent pneumonia and recurrent nontraumatic fracture differed by length of ICS use.
Notably, the number of adults in each set went down after propensity score matching (prevalent, n = 291,687; inception, n = 185,346), which the study said factored in sex, race, ethnicity, BMI, smoking status and Charlson-Deyo score dichotomized at greater than two.
New diagnosis risk
When compared with short-term ICS use, long-term ICS use in the prevalent cohort was found to significantly raise the risk for a new diagnosis of one of the five outlined outcomes (HR = 2.65; 95% CI, 2.62-2.68). The study noted that this was also true in the inception cohort, with long-term ICS users facing a significantly higher risk for one of the five conditions (HR = 2.6; 95% CI, 2.56-2.64).
Broken down by condition, the risk for each one continued to be elevated in the prevalent cohort with long-term vs. short-term ICS use: diabetes (HR = 2.56; 95% CI, 2.53-2.59), osteoporosis (HR = 2.5; 95% CI, 2.5-2.5), pneumonia (HR = 2.48; 95% CI, 2.45-2.5), cataracts (HR = 2.45; 95% CI, 2.43-2.48) and fracture (HR = 2.45; 95% CI, 2.42-2.47).
Researchers observed a similar pattern when assessing these individual risks in the inception cohort, with the risk for each one heightened with long-term vs. short-term ICS use: diabetes (HR = 2.48; 95% CI, 2.45-2.52), osteoporosis (HR = 2.44; 95% CI, 2.41-2.48), pneumonia (HR = 2.4; 95% CI, 2.37-2.44), cataracts (HR = 2.39; 95% CI, 2.36-2.43) and fracture (HR = 2.39; 95% CI, 2.36-2.42).
Reflecting on the above findings, Yawn told Healio the higher risks found with long-term ICS use were “slightly surprising.”
“Most studies have reported on adverse effects of systemic (oral, intramuscular or intravenous) corticosteroids, and the potential risks of inhaled corticosteroids are often overlooked,” Yawn told Healio. “In this very large study, the adverse outcomes were about 2.5 times as likely to occur after 24 months of ICS use compared to less than 4 months of ICS use, and they were not rare with one or more of the outcomes occurring in 29.4% of individuals.”
In terms of the specific risks studied, Pace highlighted the elevated risk for diabetes with long-term ICS use.
“Given the large sample size and known risks of ICS long-term use, we expected to have a positive finding for the combined outcomes,” Pace told Healio. “The literature was mixed about an increased risk for type 2 diabetes, so the strength of that risk was somewhat surprising.”
Using the inception cohort, researchers reported that a higher proportion of adults with long-term vs. short-term ICS use had at least one of the five conditions (29.41% vs. 9.15%). Yawn told Healio the absolute risk difference between these two groups suggests “a number needed to harm of only five.”
“The overall number needed to harm was considerably lower than I expected after 24-plus months of ICS use,” Pace told Healio.
Recurrent event risk, future research
When evaluating the risks for the recurrent events, the pattern of elevated risks with long-term ICS use continued in both cohorts.
According to the study, adults with long-term ICS use in the prevalent cohort faced a significantly higher risk for recurrent pneumonia (HR = 2.88; 95% CI, 2.62-3.16) and recurrent nontraumatic fracture (HR = 1.77; 95% CI, 1.42-2.21) than adults with short-term ICS use.
In the inception cohort, researchers also reported that the risk for each recurrent event was significantly elevated among long-term ICS users compared with short-term users: pneumonia (HR = 2.85; 95% CI, 2.53-3.22) and nontraumatic fracture (HR = 1.57; 95% CI, 1.2-2.06).
“As with all therapies, the patient and the physician or clinician need to weigh the risks and benefits before initiating treatment,” Yawn told Healio. “This information should help with those decisions.”
Considering the current state of ICS use in patients with COPD, Pace told Healio these findings could alter prescribing patterns.
“We got pushback during the review process that the reason ICS/LABA is used as a primary COPD drug is that it is inexpensive,” Pace said. “Perhaps understanding the full long-term ‘costs’ for people using ICS for COPD that have not proven the need for that particular therapy may change prescribing patterns.
“As Yawn noted, there are clear reasons to use ICS in COPD, but the pathway to get there should be through the failure of non-ICS based inhaled therapies,” Pace continued. “Too often individuals have never been tried on LABA/LAMA therapy prior to getting an ICS.”
With the results from this study in mind, Pace emphasized the importance of studying how long-term medication use impacts patients.
“We should always be willing to examine the population impact of long-term side effects of common medications,” Pace told Healio. “For instance, given that corticosteroid nasal preparations are over the counter, perhaps their impact after decades of use should be explored — an even tougher problem to examine than the ICS issues.”
Looking ahead, Yawn and Pace both said further research on this topic should investigate ICS dosing and types/products.
“In future studies, we need to include information on the dose of ICS therapy and possibly the types of ICS used, which were not available to us,” Yawn told Healio.
“Logically, one would expect some dose response curve related to the total ICS dose and perhaps to the systemic effect of different ICS products,” Pace told Healio. “This information would be helpful to delineate with better detailed fulfillment records such that total dosages over time could be calculated.
“Some of the side effects may be at least partially ameliorated with additional therapies, such as better screening, and perhaps earlier use of osteoporosis medications may also be worth further exploration,” Pace added.
For more information:
Barbara P. Yawn, MD, MSc, FAAFP, and Wilson D. Pace, MD, can be reached at pulmonology@healio.com.
Reference:
- Long-term inhaled corticosteroid use for COPD linked to serious long-term health risks. https://www.eurekalert.org/news-releases/1077851. Published March 24, 2025. Accessed March 26, 2025.