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

Table 1 Studies showing no worsening of glucose metabolism/diabetes mellitus by inhaled corticosteroid/intranasal corticosteroid

Ref.	Study design	Patient population	ICS or INS exposure	Outcomes reported
Blackburn et al[18], 2002	Population-based cohort study	38441 elderly (≥ 66 years old) ICS users versus 53845 non-ICS users	Types and doses of ICS not stated	Over 3 yr, no association of ICS with incident DM
Borsi et al[36], 2018	Non-randomized trial	35 non-diabetic adults with mild to moderate asthma	BUD ICS 320 mcg every 12 h	Over 2 mo, ICS had no effect on HbA1c, insulin level and insulin sensitivity (HOMA-IR)
Canis et al[37], 2007	Non-randomized trial	Non-diabetic adults (12 asthma, 6 COPD)	BUD ICS 400 mcg twice daily	Over 8 wk, ICS had no effect on glucose, insulin level and insulin sensitivity (HOMA-IR)
Dendukuri et al[38], 2002	Nested case-control study	Adults aged ≥ 65 yr. 1494 cases of incident DM versus 14931 controls	Various types and doses of ICS	No increased risk of incident DM
Ebden et al[39], 1989	Prospective observational study	14 normal and 24 diet controlled DM subjects	BDP 2000 mcg/d for 2 wk	Over 2 wk, ICS did not worsen glucose tolerance test results or insulin levels
Faul et al[40], 2009	Crossover RCT	12 DM patients with asthma or COPD	FP ICS 440 mcg twice daily versus no ICS	Over 6 wk, no difference in HbA1c
Flynn et al[41], 2014	Record linkage study	4305 patients with COPD in Scotland	Various types and doses of ICS	Over at least 2 yr of follow-up, ICS did not increase incident DM or worsen pre-existing DM control
Giep et al[42], 1996	RCT	19 ventilator-dependent neonates < 1500 g birthweight	BDP ICS 1 mg/kg/d via ventilator circuit	No effect on blood glucose
Kiviranta and Turpeinen[20], 1993	Prospective observational study	15 adults with uncontrolled asthma; 15 healthy controls	Up to 2000 mcg/d of BDP ICS, and up to 1600 mcg/d of BUD ICS	Over 8 mo, no change of fasting glucose and insulin
Lee et al[33], 2016	Nested case-control study using South Korean claims database	Pregnant women who delivered between 1 January 2009 and 31 December 2011. 34190 GDM cases and 170934 control subjects	Various types and doses of ICS	ICS use was not associated with increase in the risk of GDM
Lempp et al[43], 2022	Electronic medical records study	127 patients aged 18 to 80 with COPD and type 2 DM on at least 2 oral anti-glycemic medications from 1 January 2000 to 31 December 2017	ICS (64 patients) versus no ICS (63 patients). Various types and doses of ICS	Over 5 yr, no difference in rate of DM worsening to HbA1c > 10% (threshold chosen as add-on insulin would be considered)
O’Byrne et al[21], 2012	Pooled analyses of RCTs	44528 patients with asthma (60 trials) or COPD (8 trials)	BUD and fluticasone ICS at various doses	Over a mean follow-up of 210 d in asthma trials and 268 d in COPD trials, no association between ICS use and hyperglycemia or incident DM
Pauwels et al[19], 1999	RCT	1277 adults with COPD and continued smoking	BUD ICS 400 mcg/d for 3 yr versus placebo	No increase in incident DM by BUD ICS 400 mcg/d
Pu et al[44], 2021	Systematic review of 17 RCTs which reported glucose/DM data	43430 adults with COPD	Various types and doses of ICS	No difference in glucose level, DM control or incident DM between the ICS group and the control group with follow-up ranging from 12-96 wk
Rogala et al[45], 2020	Cross-sectional study	6763 adult patients with asthma and/or diabetes	Various types and doses of ICS	No association with increased fasting glucose
Rogliani et al[46], 2014	Cross-sectional study	493 outpatients with COPD, seen between 2010-2012	Types and doses of ICS not stated	No association between ICS use and DM diagnosis
Rahman et al[47], 2021	RCT	70 patients with asthma, but no DM	Fluticasone ICS (at low to high doses) versus no ICS	Over 3 mo, no difference in fasting plasma glucose, 2 h after 75 g oral glucose intake, and in HbA1c
Slatore et al[48], 2009	Prospective cohort study	1698 adults with COPD	Various types and doses of ICS	No change of serum glucose in subjects without diabetes
Turpeinen et al[49], 1991	Prospective observational study	9 children with asthma	400-800 mcg/m2/d of BUD ICS	Over 5 mo, no change of fasting glucose and insulin
Yucel et al[50], 2009	Case-control study	141 children with asthma (cases), 52 children without asthma (controls). All children did not have DM	75% of children were using on BUD ICS, and 25% of children were using FP ICS, at various doses	No significant association between cumulative dose of ICS and HbA1c

BDP: Beclomethasone dipropionate; BUD: Budesonide; CI: Confidence interval; COPD: Chronic obstructive pulmonary disease; DM: Diabetes mellitus; FP: Fluticasone propionate; GDM: Gestational diabetes mellitus; HbA1c: Glycated hemoglobin; HOMA-IR: Homeostatic Model Assessment-Insulin Resistance; ICS: Inhaled corticosteroid; INS: Intranasal corticosteroid; RCT: Randomized controlled trial.