Impact of inhaled and intranasal corticosteroids on glucose metabolism and diabetes mellitus: A mini review

Table 2 Studies showing worsening of glucose metabolism/diabetes mellitus by inhaled corticosteroid/intranasal corticosteroid

Ref.	Study design	Patient population	ICS or INS exposure	Outcomes reported
Ajmera et al[22], 2017	Retrospective study of Medicaid claims (2005-2008)	15287 adults with newly diagnosed COPD, who were diabetes free at baseline	Types and doses of ICS not stated	Over 1 yr, ICS use associated with greater risk of new-onset diabetes (adjusted OR = 1.23, 95%CI: 1.07-1.47)
Ben-Dov et al[17], 2023	Case report	9-mo-old female with type 1 DM	Off-label use of otic ciprofloxacin 0.3%/dexamethasone 0.1% drops in the nasal passage for choanal obstruction with granulation tissue	Over 7 d, average daily blood glucose increased by 86 mg/dL. Hyper-glycemic spikes resolved within 2 d after switching to mometasone furoate 0.05% spray
Faul et al[51], 1998	Case report	67-year-old asthmatic man	FP ICS 2000 mcg/d	Over 40 wk, patient developed glycosuria with rise of HbA1c to 8.2%. Glycosuria resolved and HbA1c fell to 7.0% with reduction of FP ICS to 500 mcg/d
Faul et al[52], 1999	Case report	67-year-old asthmatic man	BUD ICS 2000 mcg/d	Over 20 wk, patient developed glycosuria with rise of HbA1c to 8.2%. Glycosuria resolved and HbA1c fell to 7.2% with reduction of BUD ICS to 800 mcg/d
Gayle et al[23], 2019	Nested case-control study	220971 adults with COPD and previous smoking registered at a United Kingdom Clinical Practice Research Datalink practice (January 2010-December 2016)	Types and doses of ICS not stated	Increased incident DM (OR = 1.73, 95%CI: 1.65-1.82), adjusted for smoking status, deprivation, BMI, hypertension, coronary heart disease and heart failure
Kruszynska et al[53], 1987	Prospective observational study	9 normal adults aged 21-44 yr	BDP ICS 500 mcg twice daily	Over 4 wk, ICS use associated with increased peak blood glucose (7.1 versus 6.7 mmol/L, P < 0.01) after 75 g oral glucose load. No effect on fasting blood glucose or HbA1c
Lelii et al[54], 2016	Case report	2-year-old boy with recurrent wheezing	FP ICS 100 mcg twice daily for 2 mo before presentation with whining, agitation, and diuresis	Transient symptomatic hyperglycemia (10 mmol/L). FP ICS then replaced with montelukast
Lund et al[24], 2023	Case-only symmetry analysis of Danish national registries	348996 individuals > 40 yr with a first-ever prescription for any antidiabetic drug 1996-2018	Inhaled β2-agonists combined with glucocorticoids	Increased risk of incident diabetes (SR = 1.35, 95%CI: 1.28-1.42 and SR = 1.14, 95%CI: 1.06-1.22 in replicate analyses)
Metsälä et al[25], 2020	Nationwide, register-based case-cohort study	Children who were born January 1, 1995, through December 31, 2008, in Finland and diagnosed with type 1 DM by 2010 (n = 3342), compared with 10% random sample from each birth-year cohort (n = 80909)	Beclomethasone, BUD, fluticasone. Dose not stated	Over a median of 7.9 yr, increased risk of type 1 DM after adjusting for other anti-asthmatic drugs, asthma, sex, and birth decade (HR = 1.29, 95%CI: 1.09-1.52), if patients received high-dose ICS (> 800 mcg budesonide equivalent dose)
Mizrachi et al[16], 2012	Retrospective observational study	1768 DM patients treated with INS, with 245 patients providing HbA1c data and 163 patients providing fasting glucose data	BUD, FP, triamcinolone acetonide INS. Dose not stated	Over 3 mo, triamcinolone acetonide associated with increased fasting glucose but not with HbA1c. Other INS had no association with either glucose or HbA1c changes
Price et al[28], 2016	Matched cohort study	682 adults (≥ 40 years old) with COPD prescribed ICS in two large United Kingdom databases (1983-2016)	Types and doses of ICS not stated	Over 12-18 mo of follow-up, ICS prescription associated with increased HbA1c, with adjusted difference 0.16% (95%CI: 0.05%-0.27%) in all COPD patients, and 0.25% (95%CI: 0.10%-0.40%) in mild-to-moderate COPD patients. ICS prescription also associated with more diabetes-related general practice visits and more frequent glucose strip prescriptions. Associations were stronger for higher cumulative ICS doses (> 250 mg FP equivalent), compared to ≤ 125 mg
Price et al[26], 2019	Matched cohort study	18774 adults (≥ 40 years old) with COPD initiating ICS or long-acting bronchodilator in two large United Kingdom databases (1983-2016)	Types and doses of ICS not stated	Over a median follow-up at least 3.5 yr, ICS use associated with increased risk of incident DM (HR = 1.27, 95%CI: 1.07-1.50). ICS use also worsened DM control for high-dose ICS (mean daily dose ≥ 500 mcg FP equivalent)
Saeed et al[55], 2020	Cohort study using Danish health databases	50148 adults with COPD	Predominantly BUD (about 50%) and fluticasone (about 45%) ICS, at various doses. Other ICS (< 5%) used included beclomethasone, ciclesonide and mometasone	Over 7 yr, ICS use was associated with an increased risk of DM (HR = 1.16, 95%CI: 1.01-1.32) for high-dose ICS use (≥ 970 mcg BUD equivalent) and BMI < 30 kg/m2
Schou and Wolthers[15], 2011	Crossover RCT	17 children with asthma	BUD ICS 400 mcg daily for 1 wk	Over 1 wk, ICS use increased serum fructosamine compared to no ICS use (228.1 μmol/L versus 223.1 μmol/L, P = 0.02)
Slatore et al[48], 2009	Prospective cohort study	1698 adults with COPD, among United States veterans enrolled in 7 primary care clinics between February 1997 and December 1999	Various types (e.g., beclomethasone, flunisolide, fluticasone) and doses of ICS	Over 2-4 yr, among diabetics only, there was a 1.82 mg/dL (95%CI: 0.49-3.15) increase in serum glucose, for every 100-mcg triamcinolone equivalent/d increase in ICS dose
Ställberg et al[29], 2020	Cohort study	7078 Swedish patients with COPD using data from real-world, primary care settings	Types and doses of ICS not stated	Over at least 6 mo, ICS use, especially at high dose (≥ 640 mcg/d BUD equivalent), was associated with incident type 2 DM
Suissa et al[27], 2010	Nested case-controlled study using a Canadian health insurance database	388584 patients with respiratory disease	Various types of ICS (beclomethasone, BUD, triamcinolone, fluticasone, flunisolide), at various doses	Over 5.5 yr of follow-up, 34% increased rate of initiation of an anti-diabetic agent, especially in patients receiving high dose ICS (≥ 1000 mcg/d FP equivalent). In diabetics on oral hypoglycemic agents, ICS use increased risk of progression to insulin

BMI: Body-mass index; BUD: Budesonide; CI: Confidence interval; COPD: Chronic obstructive pulmonary disease; DM: Diabetes mellitus; OR: Odds ratio; FP: Fluticasone propionate; HR: Hazard ratio; ICS: Inhaled corticosteroid; INS: Intranasal corticosteroid; RCT: Randomized controlled trial; SR: Sequence ratio.