In the Journals

Topical corticosteroid use may increase type 2 diabetes risk

Use of potent topical corticosteroids in the preceding 4 years was more common among Danish and U.K. adults who went on to develop type 2 diabetes than among those who did not develop the disease, suggesting that use of these agents may be associated with increased risk for type 2 diabetes, according to findings from three studies published in Diabetes Care.

“Because most physicians are aware of the numerous serious side effects of prolonged systemic [corticosteroid] use (eg, type 2 diabetes), these are often prescribed with caution and for the shortest amount of time necessary,” Yuki M.F. Andersen, a PhD student in the department of dermatology and allergy at Herlev and Gentofte Hospital, University of Copenhagen in Denmark, and colleagues wrote. “Topical [corticosteroids] were initially developed primarily for short-term use, but long-term maintenance therapy is now recommended in many dermatological guidelines. Concern has previously been raised about similar diabetogenic effects with use of topical [corticosteroids], but this risk remains unclear and is therefore not considered by most physicians.”

Andersen and colleagues performed three separate studies, with two case-control studies and the other a cohort study.

Finding an association

In the first case-control study, the researchers examined data from adults in the Danish health care and administrative registries between 2007 and 2015. The researchers identified 115,218 adults with diabetes (mean age, 61.9 years; 46.2 years) and then age- and sex-matched them to the same number of adults without diabetes. The researchers then examined records dating back 4 years from diabetes diagnosis to identify corticosteroid exposure, duration and potency based on prescriptions.

More adults with type 2 diabetes were exposed to topical corticosteroids in the 4 years before diagnosis compared with those without diabetes (34.2% vs. 26.9%; P < .0001). Systemic corticosteroid use was also more frequent among those with type 2 diabetes prior to diagnosis compared with those without the condition (15.5% vs. 11%; P < .0001). The researchers found that topical corticosteroid use was positively associated with type 2 diabetes when adjusting for systemic corticosteroid use, socioeconomic status, smoking, alcohol, antihypertensive drugs, lipid-lowering drugs, inhaled corticosteroids and psoriasis (adjusted OR = 1.25; 95% CI, 1.23-1.28). Systemic corticosteroid use also had a positive association with type 2 diabetes after adjustment (aOR = 1.28; 95% CI, 1.23-1.32).

The odds of developing diabetes were higher for those who used corticosteroids for at least 2 years (aOR = 1.36; 95% CI, 1.3-1.42) compared with those who used the agents for 1 year or less before diagnosis (aOR = 1.3; 95% CI, 1.25-1.36). According to the researchers, the most potent corticosteroids were more strongly associated with development of type 2 diabetes (aOR = 1.33; 95% CI, 1.27-1.4) compared with mild doses (aOR = 1.17; 95% CI, 1.07-1.28).

In the second case-control study, the researchers evaluated data from adults (aged 26 to 89 years) who were included in the Clinical Practice Research Datalink database in the U.K. from 2007 to 2015. They identified 54,944 adults who met the criteria for type 2 diabetes and then age- and sex-matched them to the same number of individuals without diabetes (mean age, 62.1 years; 43.7% women). The researchers identified corticosteroid exposure, duration and potency over the 4 years before diabetes diagnosis

As they had in the Danish case-control study, the researchers found that more people with diabetes had previously been exposed to topical corticosteroids than those without the disease (38.2% vs. 29.5%; P < .0001). Adults with diabetes were also prescribed systemic corticosteroids more often before being diagnosed than those without diabetes (21.7% vs. 14.9%; P < .0001). The researchers further noted a similar fully adjusted positive association with type 2 diabetes for topical corticosteroid exposure (aOR = 1.23; 95% CI, 1.19-1.27), but potency did not significantly affect the results. In contrast to findings from the Danish study, using corticosteroids for at least 2 years was more weakly linked to development of type 2 diabetes (aOR = 1.26; 95% CI, 1.19-1.34) than shorter-term exposure (aOR = 1.38; 95% CI, 1.31-1.45).

Potency strongly associated

In the cohort study, the researchers looked at data from the entire adult population in Denmark from 2001 to 2015. Excluding those who previously had been diagnosed with diabetes or used corticosteroids, they identified 1,051,080 individuals who were prescribed topical corticosteroids during the study period (mean age, 46.6 years; 50.7% women) and 1,638,393 who were not (mean age, 46.2 years; 43.9% women).

Newly diagnosed type 2 diabetes was noted more frequently in those who also had corticosteroid prescriptions (incidence rate [IR] = 5.73 per 1,000 person-years; 95% CI, 5.68-5.78) compared with those without (IR = 3.56 per 1,000 person-years; 95% CI, 3.54-3.58). In addition to a positive relationship between corticosteroid use and development of type 2 diabetes in fully adjusted analysis (HR = 1.27; 95% CI, 1.26-1.29), the researchers found that the most potent doses led to the strongest association (aOR = 1.39; 95% CI, 1.35-1.42) compared with mild doses (aOR = 1.09; 95% CI, 1.05-1.14).

“These three studies of Danish and U.K. adults showed that topical [corticosteroids] are very frequently prescribed, highlighting the importance of safety assessments of these drugs,” the researchers wrote. “Clinicians should be cognizant of possible diabetogenic effects of high-potency topical [corticosteroids] and consider other treatment options if possible.” – by Phil Neuffer

Disclosures: Andersen reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

Use of potent topical corticosteroids in the preceding 4 years was more common among Danish and U.K. adults who went on to develop type 2 diabetes than among those who did not develop the disease, suggesting that use of these agents may be associated with increased risk for type 2 diabetes, according to findings from three studies published in Diabetes Care.

“Because most physicians are aware of the numerous serious side effects of prolonged systemic [corticosteroid] use (eg, type 2 diabetes), these are often prescribed with caution and for the shortest amount of time necessary,” Yuki M.F. Andersen, a PhD student in the department of dermatology and allergy at Herlev and Gentofte Hospital, University of Copenhagen in Denmark, and colleagues wrote. “Topical [corticosteroids] were initially developed primarily for short-term use, but long-term maintenance therapy is now recommended in many dermatological guidelines. Concern has previously been raised about similar diabetogenic effects with use of topical [corticosteroids], but this risk remains unclear and is therefore not considered by most physicians.”

Andersen and colleagues performed three separate studies, with two case-control studies and the other a cohort study.

Finding an association

In the first case-control study, the researchers examined data from adults in the Danish health care and administrative registries between 2007 and 2015. The researchers identified 115,218 adults with diabetes (mean age, 61.9 years; 46.2 years) and then age- and sex-matched them to the same number of adults without diabetes. The researchers then examined records dating back 4 years from diabetes diagnosis to identify corticosteroid exposure, duration and potency based on prescriptions.

More adults with type 2 diabetes were exposed to topical corticosteroids in the 4 years before diagnosis compared with those without diabetes (34.2% vs. 26.9%; P < .0001). Systemic corticosteroid use was also more frequent among those with type 2 diabetes prior to diagnosis compared with those without the condition (15.5% vs. 11%; P < .0001). The researchers found that topical corticosteroid use was positively associated with type 2 diabetes when adjusting for systemic corticosteroid use, socioeconomic status, smoking, alcohol, antihypertensive drugs, lipid-lowering drugs, inhaled corticosteroids and psoriasis (adjusted OR = 1.25; 95% CI, 1.23-1.28). Systemic corticosteroid use also had a positive association with type 2 diabetes after adjustment (aOR = 1.28; 95% CI, 1.23-1.32).

The odds of developing diabetes were higher for those who used corticosteroids for at least 2 years (aOR = 1.36; 95% CI, 1.3-1.42) compared with those who used the agents for 1 year or less before diagnosis (aOR = 1.3; 95% CI, 1.25-1.36). According to the researchers, the most potent corticosteroids were more strongly associated with development of type 2 diabetes (aOR = 1.33; 95% CI, 1.27-1.4) compared with mild doses (aOR = 1.17; 95% CI, 1.07-1.28).

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In the second case-control study, the researchers evaluated data from adults (aged 26 to 89 years) who were included in the Clinical Practice Research Datalink database in the U.K. from 2007 to 2015. They identified 54,944 adults who met the criteria for type 2 diabetes and then age- and sex-matched them to the same number of individuals without diabetes (mean age, 62.1 years; 43.7% women). The researchers identified corticosteroid exposure, duration and potency over the 4 years before diabetes diagnosis

As they had in the Danish case-control study, the researchers found that more people with diabetes had previously been exposed to topical corticosteroids than those without the disease (38.2% vs. 29.5%; P < .0001). Adults with diabetes were also prescribed systemic corticosteroids more often before being diagnosed than those without diabetes (21.7% vs. 14.9%; P < .0001). The researchers further noted a similar fully adjusted positive association with type 2 diabetes for topical corticosteroid exposure (aOR = 1.23; 95% CI, 1.19-1.27), but potency did not significantly affect the results. In contrast to findings from the Danish study, using corticosteroids for at least 2 years was more weakly linked to development of type 2 diabetes (aOR = 1.26; 95% CI, 1.19-1.34) than shorter-term exposure (aOR = 1.38; 95% CI, 1.31-1.45).

Potency strongly associated

In the cohort study, the researchers looked at data from the entire adult population in Denmark from 2001 to 2015. Excluding those who previously had been diagnosed with diabetes or used corticosteroids, they identified 1,051,080 individuals who were prescribed topical corticosteroids during the study period (mean age, 46.6 years; 50.7% women) and 1,638,393 who were not (mean age, 46.2 years; 43.9% women).

Newly diagnosed type 2 diabetes was noted more frequently in those who also had corticosteroid prescriptions (incidence rate [IR] = 5.73 per 1,000 person-years; 95% CI, 5.68-5.78) compared with those without (IR = 3.56 per 1,000 person-years; 95% CI, 3.54-3.58). In addition to a positive relationship between corticosteroid use and development of type 2 diabetes in fully adjusted analysis (HR = 1.27; 95% CI, 1.26-1.29), the researchers found that the most potent doses led to the strongest association (aOR = 1.39; 95% CI, 1.35-1.42) compared with mild doses (aOR = 1.09; 95% CI, 1.05-1.14).

“These three studies of Danish and U.K. adults showed that topical [corticosteroids] are very frequently prescribed, highlighting the importance of safety assessments of these drugs,” the researchers wrote. “Clinicians should be cognizant of possible diabetogenic effects of high-potency topical [corticosteroids] and consider other treatment options if possible.” – by Phil Neuffer

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Disclosures: Andersen reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.