The effect of DPP-4 inhibitors on asthma control: an administrative database study to evaluate a potential pathophysiological relationship

Figures & data

Table 1 Patient characteristics

Characteristic	DPP-4i N=3,973	Non-DPP-4i N=7,487	p-value
Age (Mean, SD)1	53.7 (10.5)	53.4 (10.3)	0.150
Sex (N, %)1			0.563
Male	1,244 (31.3%)	2,305 (30.8%)
Female	2,729 (68.7%)	5,182 (69.2%)
Health insurance plan type (N, %)			<0.001
Comprehensive	304 (7.7%)	551 (7.4%)
EPO	50 (1.3%)	81 (1.1%)
HMO	514 (12.9%)	1,374 (18.4%)
POS	320 (8.1%)	571 (7.6%)
PPO	2,410 (60.7%)	4,308 (57.5%)
POS with capitation	25 (0.6%)	32 (0.4%)
CDHP	161 (4.1%)	210 (2.8%)
HDHP	48 (1.2%)	76 (1.0%)
Other/unknown	141 (3.5%)	284 (3.8%)
Payer (N, %)			0.414
Commercial	3,487 (87.8%)	6,610 (88.3%)
Medicare	486 (12.2%)	877 (11.7%)
Geographic region (N, %)			<0.001
Northeast	871 (21.9%)	1,172 (15.7%)
North Central	857 (21.6%)	1,786 (23.9%)
South	1,604 (40.4%)	2,950 (39.4%)
West	604 (15.2%)	1,509 (20.2%)
Unknown	37 (0.9%)	70 (0.9%)
Population density (N, %)			0.502
Urban	3,384 (85.2%)	6,320 (84.4%)
Rural	554 (13.9%)	1,104 (14.7%)
Unknown	35 (0.9%)	63 (0.8%)
Index year (N, %)			<0.001
2006	38 (1.0%)	215 (2.9%)
2007	374 (9.4%)	1,067 (14.3%)
2008	410 (10.3%)	916 (12.2%)
2009	405 (10.2%)	1,051 (14.0%)
2010	562 (14.1%)	1,203 (16.1%)
2011	745 (18.8%)	1,119 (14.9%)
2012	686 (17.3%)	926 (12.4%)
2013	623 (15.7%)	792 (10.6%)
2014	130 (3.3%)	198 (2.6%)

Notes:

1 Used in direct matching. The bold value denotes statistical significance (p<0.05).

Abbreviations: CDHP, consumer-driven health plan; DPP-4i, DPP-4 inhibitor; EPO, exclusive provider organization; HDHP, high deductible health plan; HMO, health maintenance organization; POS, point-of-service; PPO, preferred provider organization.

Table 2 Baseline health status and comorbid conditions

Clinical characteristic	DPP-4i N=3,973	Non-DPP-4i N=7,487	p-value
General health status
Deyo-Charlson Comorbidity Index (Mean, SD)	2.22 (1.2)	2.11 (1.1)	<0.0001
Adapted Diabetes Complication Score Index (Mean, SD)1	0.53 (1.0)	0.49 (0.9)	0.015
Comorbid conditions
Hypertension	2,700 (68.0%)	4,927 (65.8%)	0.020
Dyslipidemia	2,443 (61.5%)	4,215 (56.3%)	<0.0001
Rhinitis	1,091 (27.5%)	1,801 (24.1%)	<0.0001
Gastroesophageal reflux disease	540 (13.6%)	925 (12.4%)	0.059
Atherosclerosis	380 (9.6%)	633 (8.5%)	0.046
Ischemic heart disease	349 (8.8%)	633 (8.5%)	0.549
Eczema	348 (8.8%)	567 (7.6%)	0.026
Depression	344 (8.7%)	729 (9.7%)	0.059
Anxiety	284 (7.1%)	522 (7.0%)	0.726
Diabetic peripheral neuropathy	178 (4.5%)	323 (4.3%)	0.679
Diabetic retinopathy	168 (4.2%)	320 (4.3%)	0.909
Smoking2	105 (2.6%)	223 (3.0%)	0.305
Heart failure	98 (2.5%)	171 (2.3%)	0.539
Peripheral vascular disease	87 (2.2%)	121 (1.6%)	0.029
Renal impairment	75 (1.9%)	143 (1.9%)	0.934
Obesity	54 (1.4%)	96 (1.3%)	0.730
Diabetic nephropathy	52 (1.3%)	130 (1.7%)	0.082
Stroke	48 (1.2%)	63 (0.8%)	0.057
Psoriasis	46 (1.2%)	87 (1.2%)	0.984
Unstable angina pectoris	35 (0.9%)	81 (1.1%)	0.307
Pulmonary hypertension	25 (0.6%)	41 (0.5%)	0.583
Percutaneous coronary intervention	18 (0.5%)	39 (0.5%)	0.623
Anaphylaxis	16 (0.4%)	39 (0.5%)	0.384
Myocardial infarction	15 (0.4%)	43 (0.6%)	0.158
Coronary artery bypass graft	6 (0.2%)	13 (0.2%)	0.777

Notes:

1 Used in direct matching;

2 claims-based history of tobacco use/tobacco dependence. The bold value denotes statistical significance (p<0.05).

Abbreviation: DPP-4i, DPP-4 inhibitor.

Table 3 Baseline medication utilization

Medication utilization	DPP-4i N=3,973	Non-DPP-4i N=7,487	p-value
Asthma-related medications
Number of acute oral corticosteroid courses1 (N, %)			0.324
0	2,507 (63.1%)	4,834 (64.6%)
1	942 (23.7%)	1,737 (23.2%)
2	287 (7.2%)	518 (6.9%)
≥3	237 (6.0%)	398 (5.3%)
Mean SABA daily dose, albuterol equivalents1 (N, %)			0.833
0 µg	1,751 (44.1%)	3,340 (44.6%)
1–100 µg	1,566 (39.4%)	2,981 (39.8%)
101–200 µg	284 (7.1%)	502 (6.7%)
201–300 µg	172 (4.3%)	318 (4.2%)
301–400 µg	46 (1.2%)	75 (1.0%)
>400 µg	154 (3.9%)	271 (3.6%)
Mean ICS daily dose, fluticasone propionate equivalents1 (N, %)			0.166
0 µg	2,201 (55.4%)	4,210 (56.2%)
1–199 µg	1,562 (39.3%)	2,951 (39.4%)
200–399 µg	169 (4.3%)	276 (3.7%)
400–599 µg	38 (1.0%)	46 (0.6%)
600–799 µg	1 (0.0%)	1 (0.0%)
≥800 µg	2 (0.1%)	3 (0.0%)
Number of asthma prescriptions, control medications (N, %)			<0.0001
0	1,639 (41.3%)	3,238 (43.2%)
1	630 (15.9%)	1,310 (17.5%)
2	317 (8.0%)	713 (9.5%)
3	299 (7.5%)	470 (6.3%)
4	274 (6.9%)	410 (5.5%)
≥5	814 (20.5%)	1,346 (18.0%)
Number of asthma prescriptions, rescue medications (N, %)			0.130
0	1,685 (42.4%)	3,163 (42.2%)
1	1,241 (31.2%)	2,447 (32.7%)
2	502 (12.6%)	954 (12.7%)
≥3	545 (13.7%)	923 (12.3%)
Number of antibiotic courses for LRTI (N, %)			0.702
0	3,727 (93.8%)	7,061 (94.3%)
1	224 (5.6%)	387 (5.2%)
2	17 (0.4%)	28 (0.4%)
≥3	5 (0.1%)	11 (0.1%)
Acetaminophen (N, %)	1,454 (36.6%)	2,882 (38.5%)	0.046
Non-steroidal anti-inflammatory drugs (N, %)	1,168 (29.4%)	2,162 (28.9%)	0.558
Beta-blockers (N, %)	822 (20.7%)	1,609 (21.5%)	0.318
Diabetes medications (N, %)
Alpha-glucosidase inhibitors	0 (0%)	2 (0%)	0.547
Amylin analogs	1 (0%)	1 (0%)	1.000
Biguanides (metformin)	2,337 (58.8%)	3,952 (52.8%)	<0.0001
Glucagon-like peptide-1 receptor agonists	12 (0.3%)	8 (0.1%)	0.017
Insulins2	312 (7.9%)	647 (8.6%)	0.147
Short-acting	154 (3.9%)	348 (4.6%)	0.055
Long-acting	254 (6.4%)	502 (6.7%)	0.522
Combination	53 (1.3%)	120 (1.6%)	0.261
Meglitinides and combinations	3 (0.1%)	4 (0.1%)	0.700
Sodium-glucose co-transporter 2 inhibitors and combinations	0 (0%)	0 (0%)	n/a
Sulfonylureas and combinations	25 (0.6%)	63 (0.8%)	0.216
Thiazolidinediones and combinations	36 (0.9%)	57 (0.8%)	0.411

Notes:

1 Used in direct matching;

2 percent of patients using different insulin types is not mutually exclusive. The bold value denotes statistical significance (p<0.05).

Abbreviations: DPP-4i, DPP-4 inhibitor; ICS, inhaled corticosteroids; LRTI, lower respiratory tract infection; n/a, not applicable; SABA, short-acting beta agonist.

Table 4 Baseline asthma control

Clinical characteristic	DPP-4i N=3,973	Non-DPP-4i N=7,487	p-value
Risk-domain asthma control (N, %)
Patients with no inpatient admission, emergency department, or outpatient hospital visit for asthma	3,133 (78.9%)	5,728 (76.5%)	0.004
Patients with no inpatient admission, emergency department, or outpatient hospital visit for LRTI	3,816 (96.0%)	7,074 (94.5%)	<0.001
Patients with no outpatient consultation for LRTI with a resultant antibiotic prescription	3,748 (94.3%)	7,119 (95.1%)	0.085
Patients with no prescriptions for an acute course of oral corticosteroids	2,507 (63.1%)	4,834 (64.6%)	0.120
Patients meeting all of the above criteria indicating risk-domain asthma control	1,943 (48.9%)	3,655 (48.8%)	0.929
Overall asthma control (N, %)
Patients with risk-domain asthma control and limited SABA use (daily dose ≤180 µg albuterol equivalents)	1,781 (44.8%)	3,353 (44.8%)	0.965
Number of severe asthma exacerbations (N, %)			0.146
0	2,264 (57.0%)	4,303 (57.5%)
1	1,162 (29.2%)	2,198 (29.4%)
2	320 (8.1%)	631 (8.4%)
≥3	227 (5.7%)	355 (4.7%)
Number of asthma consultations without acute oral corticosteroids (N, %)1			0.007
0	1,093 (27.5%)	2,174 (29.0%)
1	1,727 (43.5%)	3,345 (44.7%)
2	662 (16.7%)	1,182 (15.8%)
≥3	491 (12.4%)	786 (10.5%)

Notes:

1 Used in direct matching. The bold value denotes statistical significance (p<0.05).

Abbreviations: DPP-4i, DPP-4 inhibitor; LRTI, lower respiratory tract infection; SABA, short-acting beta agonist.

Figure 1 Adjusted odds of risk-domain asthma control, overall asthma control, and treatment stability during follow-up.

Note: Models adjusted for health plan type, payer, geographic region, population density, index year, anaphylaxis, anxiety, depression, eczema, gastroesophageal reflux disease, ischemic heart disease, obesity, psoriasis, pulmonary hypertension, rhinitis, smoking, dyslipidemia, hypertension, renal impairment, baseline type 2 diabetes, number of asthma control medication prescriptions, number of asthma rescue medication prescriptions, number of antibiotic courses to treat LRTI, acetaminophen utilization, NSAID utilization, beta blocker utilization, microvascular complications of diabetes, macrovascular complications of diabetes, baseline biguanide utilization, baseline insulin utilization, baseline utilization of other antihyperglycemic medications, baseline DCI, baseline risk-domain asthma control, baseline overall asthma control, baseline number of severe asthma exacerbations and number of asthma consultations with acute OCS prescriptions.
Abbreviations: DCI, Deyo-Charlson Comorbidity Index; LRTI, lower respiratory tract infection; NSAID, non-steroidal anti-inflammatory drugs; OCS, oral corticosteroid; OR, odds ratio.

Figure 2 Adjusted mean estimate rate of severe asthma exacerbations during follow-up.

Note: Models adjusted for health plan type, payer, geographic region, population density, index year, anaphylaxis, anxiety, depression, eczema, gastroesophageal reflux disease, ischemic heart disease, obesity, psoriasis, pulmonary hypertension, rhinitis, smoking, dyslipidemia, hypertension, renal impairment, baseline type 2 diabetes, number of asthma control medication prescriptions, number of asthma rescue medication prescriptions, number of antibiotic courses to treat LRTI, acetaminophen utilization, NSAID utilization, beta blocker utilization, microvascular complications of diabetes, macrovascular complications of diabetes, baseline biguanide utilization, baseline insulin utilization, baseline utilization of other antihyperglycemic medications, baseline DCI, baseline risk-domain asthma control, baseline overall asthma control, baseline number of severe asthma exacerbations and number of asthma consultations with acute OCS prescriptions.
Abbreviations: DCI, Deyo-Charlson Comorbidity Index; DPP-4i, DPP-4 inhibitor; LRTI, lower respiratory tract infection; NSAID, non-steroidal anti-inflammatory drugs; OCS, oral corticosteroid.

Table 5 Follow-up asthma control

Clinical characteristic	DPP-4i N=3,973	Non-DPP-4i N=7,487	p-value
Risk-domain asthma control (N, %)
Patients with no inpatient admission, emergency department, or outpatient hospital visit for asthma	3,629 (91.3%)	6,717 (89.7%)	0.005
Patients with no inpatient admission, emergency department, or outpatient hospital visit for LRTI	3,884 (97.8%)	7,266 (97.0%)	0.025
Patients with no outpatient consultation for LRTI with a resultant antibiotic prescription	3,793 (95.5%)	7,173 (95.8%)	0.398
Patients with no prescriptions for an acute course of oral corticosteroids	2,917 (73.4%)	5,538 (74.0%)	0.526
Patients meeting all of the above criteria indicating risk-domain asthma control	2,607 (65.6%)	4,894 (65.4%)	0.788
Overall asthma control (N, %)
Patients with risk-domain asthma control and limited SABA use (daily dose ≤180 µg albuterol equivalents)	2,404 (60.5%)	4,533 (60.5%)	0.970
Treatment stability
Patients with risk-domain asthma control and no asthma medication treatment change	2,108 (49.0%)	6.098 (48.2%)	0.360
Number of severe asthma exacerbations (N, %)			0.951
0	2,823 (71.1%)	5,314 (71.0%)
1	757 (19.1%)	1,420 (19.0%)
2	235 (5.9%)	462 (6.2%)
≥3	158 (4.0%)	291 (3.9%)

Note: The bold value denotes statistical significance (p<0.05).

Abbreviations: DPP-4i, DPP-4 inhibitor; LRTI, lower respiratory tract infection; SABA, short-acting beta agonist.