Real-world medication persistence and outcomes associated with basal insulin and glucagon-like peptide 1 receptor agonist free-dose combination therapy in patients with type 2 diabetes in the US

Figures & data

Figure 1 (A) Participant flow chart. (B) Schematic of study design.

Notes: *The initiation of the second drug in the combination therapy (eg, insulin plus GLP-1, or GLP-1 plus insulin) is defined as the index event, with the corresponding date as the index date. To ensure that patients received combination therapy after the index date, they were required to have ≥14 days of overlap for both therapies in the 90 days after the index date.
Abbreviations: T2D, type 2 diabetes; GLP-1, glucagon-like peptide-1.

Table 1 Baseline demographic and clinical characteristics

Characteristics	Total (n=7,320)	Persistent (n=1,238)	Nonpersistent (n=6,082)	P-valuea
Age in years, mean (SD)	56.9 (10.4)	57.8 (9.4)	56.7 (10.5)	<0.001
Female, % (n)	50.2 (3,674)	43.9 (543)	51.5 (3,131)	<0.001
CCI score, mean (SD)	2.01 (1.71)	1.86 (1.70)	2.04 (1.72)	<0.001
Comorbidity, % (n)
Hypertension	67.1 (4,909)	62.9 (779)	67.9 (4,130)	<0.001
Cardiovascular disease	71.5 (5,231)	67.0 (830)	72.4 (4,401)	<0.001
Renal disease	8.8 (644)	8.7 (108)	8.8 (536)	0.920
A1Cb, %, mean (SD)	8.89 (1.83)	8.59 (1.67)	8.94 (1.85)	0.006
Hypoglycemia during the baseline period, % (n)	5.2 (380)	3.6 (45)	5.5 (335)	0.007
GLP-1 RA % (n)
Exenatide	23.7 (1,734)	25.2 (312)	23.4 (1,422)	0.169
Liraglutide	8.0 (586)	7.6 (94)	8.1 (492)	0.557
Basal insulin, % (n)
Insulin glargine	39.4 (2,881)	39.8 (493)	39.3 (2,388)	0.714
Insulin detemir	12.5 (917)	12.6 (156)	12.5 (761)	0.932
NPH insulin	3.1 (226)	2.5 (31)	3.2 (195)	0.193
Concomitant antihyperglycemic medicine, % (n)
Metformin	57.3 (4,194)	56.9 (704)	57.4 (3,490)	0.738
Sulfonylurea	36.7 (2,686)	37.8 (468)	36.5 (2,218)	0.375
DPP-4 inhibitor	16.5 (1,208)	16.8 (208)	16.4 (1,000)	0.756
Thiazolidinedione	20.4 (1,497)	22.0 (273)	20.1 (1,224)	0.126
Meglitinides	2.4 (177)	3.2 (39)	2.3 (138)	0.066
α-Glucosidase inhibitor	0.68 (50)	0.65 (8)	0.69 (42)	0.863
All-cause health care resource utilization, mean (SD)
Number of admissions	0.09 (0.37)	0.08 (0.36)	0.09 (0.38)	0.250
Number of outpatient claims	9.53 (11.06)	8.84 (12.04)	9.66 (10.85)	0.018
Number of ED claims	0.27 (1.30)	0.18 (0.94)	0.29 (1.36)	0.010
Diabetes-related health care resource utilization, mean (SD)
Number of admissions	0.05 (0.25)	0.04 (0.19)	0.06 (0.26)	0.017
Number of outpatient claims	4.30 (6.54)	4.07 (7.29)	4.34 (6.37)	0.185
Number of ED claims	0.06 (0.38)	0.04 (0.30)	0.06 (0.40)	0.174
All-cause health care resource costs in $, mean (SD)
Inpatient and outpatient costs	13,529 (46,717)	10,972 (34,691)	14,049 (48,789)	0.035
ED costs	263 (2,019)	204 (2,070)	275 (2,008)	0.263
Prescription costs	3,499 (3,533)	3,793 (3,509)	3,439 (3,535)	0.001
Diabetes-related health care resource costs in $, mean (SD)
Inpatient and outpatient costs	5,815 (28,023)	4,357 (22,326)	6,112 (29,039)	0.045
ED costs	114 (1,091)	63 (539)	124 (1,171)	0.072
Prescription costs	1,414 (1,331)	1,624 (1,493)	1,372 (1,291)	<0.001

Notes:

a Persistent vs nonpersistent;

b defined as the last A1C value during the baseline period or <15 days after the index date; if multiple A1C values were available, the measurement closest to the index date was used in the analysis.

Abbreviations: A1C, glycated hemoglobin A_1c; CCI, Charlson Comorbidity Index; DPP-4, dipeptidyl peptidase; ED, emergency department; GLP-1 RA, glucagon-like peptide-1 receptor agonist; SD, standard deviation.

Figure 2 Kaplan–Meier curve of median time to discontinuation of combination therapy.

Table 2 Health care utilization in the 12-month follow-up period

Characteristics	Total (n=7,320)	Persistent (n=1,238)	Nonpersistent (n=6,082)	P-valuea
All-cause, mean (SD)
Number of admissions	0.24 (0.72)	0.18 (0.61)	0.25 (0.74)	0.003
Number of outpatient claims	22.69 (21.95)	23.01 (24.66)	22.62 (21.36)	0.571
Number of ED claims	0.67 (2.91)	0.54 (2.37)	0.70 (3.01)	0.074
Length of in-hospital stay (days)	1.30 (6.62)	0.86 (5.17)	1.39 (6.88)	0.011
Diabetes-related, mean (SD)
Number of admissions	0.13 (0.43)	0.10 (0.37)	0.14 (0.44)	0.006
Number of outpatient claims	9.35 (11.80)	9.44 (15.04)	9.33 (11.03)	0.760
Number of ED claims	0.12 (0.65)	0.10 (0.64)	0.12 (0.66)	0.266
Length of in-hospital stay (days)	0.53 (2.76)	0.35 (1.69)	0.57 (2.93)	0.014

Note:

a Persistent vs nonpersistent.

Abbreviations: ED, emergency department; SD, standard deviation.

Figure 3 All-cause (A) and diabetes-related (B) health care costs over the 12 months of follow-up.

Abbreviation: ED, emergency department.

Table 3 Predictors of A1C change

Predictor	Estimate (%)	SE	95% CI	P-value
Persistent (vs nonpersistent)	−0.5689	0.1516	−0.8661, −0.2717	0.002
Age (per year)	−0.0028	0.0068	−0.0161, 0.0105	0.678
Female (vs male)	−0.0835	0.1166	−0.3119, 0.1450	0.474
US region (vs South)
Midwest	0.2129	0.2206	−0.2195, 0.6453	0.335
Northeast	0.1120	0.2262	−0.3312, 0.5553	0.620
Unknown	0.3471	0.5706	−0.7712, 1.4653	0.543
West	0.1384	0.1570	−0.1693, 0.4461	0.378
Health plan type (vs point of service)
Health Maintenance Organization	0.0040	0.1573	−0.3044, 0.3124	0.980
Exclusive Provider Organization	0.0174	0.1717	−0.3190, 0.3539	0.919
Indemnity	−0.0851	1.0411	−2.1257, 1.9555	0.935
Preferred Provider Organization	0.5761	0.3446	−0.0994, 1.2515	0.095
Other	0.0316	0.2707	−0.4990, 0.5621	0.907
CCI score (vs 0)
1–2	−0.3561	0.3495	−1.0411, 0.3288	0.308
3–4	−0.4984	0.3634	−1.2107, 0.2139	0.170
≥5	−0.2046	0.3892	−0.9674, 0.5581	0.599
Baseline hypoglycemia (yes vs no)	0.1649	0.3050	−0.4330, 0.7628	0.589
Baseline hypertension (yes vs no)	0.0315	0.1467	−0.2560, 0.3190	0.830
Baseline lipid disease (yes vs no)	−0.0569	0.1667	−0.3837, 0.2699	0.733
Baseline A1C (per %)	−0.5293	0.0331	−0.5943, −0.4643	<0.001
Baseline usage of any OAD (yes vs no)	−0.1685	0.1435	−0.4497, 0.1126	0.240
Baseline usage of basal insulin (yes vs no)	−0.1724	0.2060	−0.5761, 0.2313	0.403
Baseline usage of any GLP-1 RA (yes vs no)	−0.3094	0.2186	−0.7379, 0.1191	0.157
Baseline all-cause total health care encounter charges (per $)	<0.0001	<0.0001	<0.0001, <0.0001	0.497

Abbreviations: A1C, glycated hemoglobin A_1c; CCI, Charlson Comorbidity Index; CI, confidence interval; GLP-1 RA, glucagon-like peptide-1 receptor agonist; OAD, oral antidiabetes drug; SE, standard error.