Healthcare Costs and Adherence Associated With Human Regular U-500 Versus High-Dose U-100 Insulin in Patients With Diabetes

Elizabeth L. Eby, MPH; Anthony J. Zagar, MS; Ping Wang, PhD; Bradley H. Curtis, PhD; Jin Xie, MS; Diane C. Haldane, MS; Iskandar Idris, MD; Anne L. Peters, MD; Robert C. Hood, MD; Jeffrey A. Jackson, MD

Disclosures

Endocr Pract. 2014;20(7):663-670.

Abstract and Introduction

Abstract

Objective: Describe the characteristics, costs, and adherence of patients receiving human regular U-500 insulin (U-500R) compared with those of patients receiving high-dose (≥150 units/day) U-100 insulin.

Methods: Data from Truven Health MarketScan Research Databases, July 1, 2008, through December 31, 2010, were used. The U-100 cohort received ≥150 units/day of U-100 insulin for ≥31 days during the first 60 days after the index date. The U-500R cohort received ≥2 prescriptions of U-500R after the index date. Analyses were performed on propensity-matched cohorts. The changes in annualized costs were compared between the 2 cohorts using paired t tests. Adherence was assessed by the proportion of days covered (PDC) and compared using a 2-sample t test. Glycemic efficacy data were not available in this database.

Results: There were 1,044 U-500R–treated patients (19.1% with type 1 diabetes [T1D]) and 11,520 U-100– treated patients (23.8% with T1D) identified, from which 1,039 matched pairs were obtained. The mean decrease of $1,290 in annual pharmacy costs for the U-500R cohort was significantly different from the mean increase of $2,586 for the U-100 cohort (P<.001; 95% confidence interval, –$4,345 to –$3,422). More U-500R patients experienced hypoglycemia (17.3% vs. 11.8%; P<.001), but the hypoglycemia rate per person and related costs were not significantly different between cohorts. Finally, the mean 12-month PDC was 65.0% for U-500R versus 47.6% for U-100 patients (P<.0001).

Conclusion: Compared with treatment with ≥150 units/day of U-100 insulin, treatment with U-500R was associated with decreases in pharmacy costs, a higher percentage of patients experiencing hypoglycemia, and greater treatment adherence.

Introduction

The rising global incidence of diabetes and obesity creates challenges for clinicians in managing the increasing numbers of patients who require high doses of insulin to achieve glycemic goals.^[1–6] Severe insulin resistance (insulin requirements of >2 units/kg/day or >200 units/day [4,5]) occurs in patients with type 1 diabetes (T1D) and patients with type 2 diabetes (T2D) who inject large volumes of prandial/basal insulins that may call for 8 or more separate injections per day. Despite increasing use of human regular U-500 insulin (U-500R; 500 U/mL: Humulin® R U-500; Eli Lilly and Company, Indianapolis, IN),^[7] limited data exist regarding the characteristics of patients requiring high-dose insulin and their clinical and economic outcomes. The objectives of this study were to describe the characteristics, healthcare costs (including those of hypoglycemic events), and adherence of U.S. patients receiving U-500R compared with patients receiving high doses (≥150 units/day) of U-100 insulins for treatment of diabetes.

1 2 3 4 5

Next Section

Abstract and Introduction
Methods
Results
Discussion
Conclusion
References

Table 1. Demographic and Clinical Characteristics of Patients in the Preperiod or at Index ^a
Characteristics		Prematched			Postmatched
Characteristics		U-500R (n = 1,044)	U-100 (n = 11,520)	Std. Diff.	U-500R (n = 1,039)	U-100 (n = 1,039)	Std. Diff.
Gender, n (%)	Female	453 (43.4)	4,809 (41.7)	0.033	452 (43.5)	466 (44.9)	0.027
Gender, n (%)	Male	591 (56.6)	6,711 (58.3)	0.033	587 (56.5)	573 (55.1)	0.027
Age at Index Date	Mean (SD)	55.1 (10)^d	56.3 (12.2)	0.107	55.1 (10)	55.5 (10.7)	0.04
Region, n (%)	North Central	301 (28.8)^c	3,893 (33.8)	0.107	301 (29.0)	278 (26.8)	0.049
	North East	80 (7.7)	938 (8.1)	0.018	80 (7.7)	72 (6.9)	0.03
	South	492 (47.1)	5,018 (43.6)	0.072	490 (47.2)	519 (50.0)	0.056
	West	171 (16.4)	1,671 (14.5)	0.052	168 (16.2)	170 (16.4)	0.005
Enrolled Database, n (%)	Commercial	909 (87.1)^d	9,105 (79.0)	0.215	904 (87.0)	892 (85.9)	0.034
Enrolled Database, n (%)	Medicare	135 (12.9)	2,415 (21.0)	0.215	135 (13.0)	147 (14.1)	0.034
CCI Score	Mean (SD)	2.3 (1.7)^d	2.0 (1.6)	0.209	2.3 (1.7)	2.3 (1.8)	0.015
Prescriber: Endocrinologist	n (%)	490 (46.9)^d	2,868 (24.9)	0.472	485 (46.7)	471 (45.3)	0.027
Inpatient Admissions	n (%)	174 (16.7)^d	1,427 (12.4)	0.122	170 (16.4)	165 (15.9)	0.013
Diabetes Type, n (%)	Type 1	199 (19.1)^d	2,738 (23.8)	0.115	198 (19.1)	196 (18.9)	0.005
Diabetes Type, n (%)	Type 2	845 (80.9)	8,782 (76.2)	0.115	841 (80.9)	843 (81.1)	0.005
Comorbidities and Complications, n (%)	Hypoglycemia	93 (8.9)	794 (6.9)	0.075	92 (8.9)	91 (8.8)	0.003
	Cardiovascular	306 (29.3)^d	2,715 (23.6)	0.13	301 (29.0)	279 (26.9)	0.047
	Cerebrovascular	53 (5.1)	513 (4.5)	0.029	53 (5.1)	62 (6.0)	0.038
	Hypertension	474 (45.4)^d	4,252 (36.9)	0.173	469 (45.1)	466 (44.9)	0.006
	Nephropathy	198 (19.0)^d	1,646 (14.3)	0.126	196 (18.9)	187 (18.0)	0.022
	Neuropathy	273 (26.1)^d	1,980 (17.2)	0.219	269 (25.9)	286 (27.5)	0.037
	Retinopathy	119 (11.4)	1,098 (9.5)	0.061	117 (11.3)	101 (9.7)	0.05
	Obesity	89 (8.5)^d	576 (5.0)	0.141	89 (8.6)	96 (9.2)	0.024
	Lower Limb Amputation	3 (0.3)	27 (0.2)	0.01	2 (0.2)	5 (0.5)	0.05
	Depression	62 (5.9)	598 (5.2)	0.033	60 (5.8)	71 (6.8)	0.044
	Bariatric Surgery	38 (3.6)^b	297 (2.6)	0.061	36 (3.5)	36 (3.5)	0.00
	CSII (pump)	269 (25.8)^d	1,571 (13.6)	0.309	264 (25.4)	276 (26.6)	0.026
Prior Medication Use, n (%)	OAD	543 (52.0)	5,683 (49.3)	0.054	541 (52.1)	543 (52.3)	0.004
Prior Medication Use, n (%)	Non-Insulin Injectable	187 (17.9)^d	1,344 (11.7)	0.177	185 (17.8)	207 (19.9)	0.054
Total Health Care Costs ($)	Mean (SD)	14,871.8^d (26,263.4)	10,774.2 (17,971.8)	0.107	14,238 (22,809.1)	13,915.9 (22,295.7)	0.04

Abbreviations: CCI = Charlson comorbidity index; CSII = continuous subcutaneous insulin infusion; OAD = oral antidiabetic drug;
Std. Diff. = standardized difference; U-100 = regular U-100 insulin (total daily dose ≥150 units);
U-500R = human regular U-500 insulin.
^aFor categorical variables, P values are from a chi-square test. For continuous variables, P values are from 2-sample t tests.
^b P<.05.
^c P<.01.
^d P<.001.

Table 2. Costs for Matched Cohorts in the Preperiod and the Postperiod
Costs ($/Year)	U-500R (n = 1,039) Mean (SD)^a			U-100 (n = 1,039) Mean (SD)^a
Costs ($/Year)	Preperiod	Postperiod	Post – Pre	Preperiod	Postperiod	Post – Pre
Medical: diabetes-related
Inpatients	1,245 (8,470)	2,325 (10,373)	1,080 (12,030)^c	1,941 (9,895)	2,342 (13,092)	402 (14,172)
Outpatients	3,992 (11,655)	3,253 (4,935)	−739 (11,833)^b	3,443 (8,340)	2,852 (5,021)	−591 (8,682)^b
Emergency Room	154 (709)	248 (883)	94 (993)^c	195 (946)	164 (648)	−30 (1,028)
Medical: diabetesrelated	5,391 (15,378)	5,826 (12,836)	435 (17,835)	5,579 (13,468)	5,359 (16,323)	−220 (18,240)
Medical: non-diabetes-related
Inpatients	5,106 (26,486)	6,058 (20,391)	952 (30,644)	4,199 (24,671)	5,192 (25,335)	993 (34,329)
Outpatients	7,840 (18,332)	9,551 (17,255)	1,711 (18,741)^c	9,287 (25,887)	9,531 (19,331)	243 (22,371)
Emergency Room	377 (1,503)	541 (1,532)	164 (1,860)^c	366 (1,417)	415 (1.189)	49 (1,579)
Medical: non–diabetes-related	13,323 (39,267)	16,150 (30,831)	2,827 (41,786)	13,852 (39,080)	15,138 (39,089)	1,285 (41,991)
Total Medical
Inpatient	6,351 (28,223)	8,383 (25,071)	2,032 (34,372)	6,140 (27,174)	7,535 (34,890)	1,395 (40,702)
Outpatient	11,832 (23,003)	12,803 (19,095)	972 (23,018)	12,730 (28,408)	12,383 (21,283)	−348 (25,565)
Emergency Room	531 (1,731)	789 (1,914)	258 (2,070)^d	560 (1,921)	579 (1,457)	18 (1,965)
Total Medical	18,714 (43,805)	21,975 (36,499)	3,262 (47,527)	19,431 (43,791)	20,496 (50,306)	1,065 (50,678)
Pharmacy
Insulin: U-500R	0 (0)	2,285 (1,301)	2,285 (1,301)^d	0 (0)	0 (0)	0 (0)
Insulin: U-100	4,182 (3,422)	631 (1,636)	–3,551 (3,382)^d	3,033 (2,077)	5,232 (2,785)	2,199 (2,302)^d
Insulin: U-500R + U-100	4,182 (3,422)	2,917 (1,998)	–1,266 (3,041)^d	3,033 (2,077)	5,232 (2,785)	2,199 (2,302)^d
OAD	330 (673)	202 (491)	–128 (542)^d	403 (766)	349 (740)	−54 (579)^c
Noninsulin Injectables	392 (1,270)	269 (893)	–122 (1,172)^c	335 (932)	288 (888)	−47 (748)^b
Other	4,858 (6,105)	5,084 (6,131)	226 (4,146)	4,630 (4,835)	5,117 (5,744)	487 (3,812)^d
Pharmacy	9,762 (7,899)	8,472 (6,933)	–1,290 (5,754)^d	8,401 (5,795)	10,987 (6,909)	2,586 (4,703)^d
Medical and Pharmacy Costs	28,476 (45,618)	30,447 (38,172)	1,971 (47,910)	27,832 (44,591)	31,483 (51,350)	3,651 (50,934)^b

Abbreviations: OAD = oral antidiabetic drug; U-100 = regular U-100 insulin (total daily dose ≥150 units); U-500R = human regular U-500 insulin.
^aData are presented as mean and SD; P values are from paired t tests.
^b P<.05.
^c P<.01.
^d P<.001.

Table 3. Difference-in-Differences Annual Medical Costs for all Patients ^a
Cost ($/Year)	U-500RDiff – U-100Diff Mean (SD) (n = 1,039)	P Values		95% CI
Cost ($/Year)	U-500RDiff – U-100Diff Mean (SD) (n = 1,039)	Paired t test	Nonparametric Bootstrap	Nonparametric Bootstrap	PSBBb
Medical: Diabetes-Related	655 (25,216)	.403	.3986	(–954, 2,147)	(–1,160, 1,153)
Medical: Non–Diabetes-Related	1,542 (59,566)	.404	.3992	(–2,062, 4,991)	(–1,713, 3,118)
Medical: Total	2,196 (69,358)	.308	.3035	(–2,037, 6,216)	(–1,963, 3,572)
Pharmacy	–3,876 (7,553)	<.0001	<.0001	(–4,345, –3,422)	(–1,597, –881)
Medical and Pharmacy Costs	–1,680 (70,026)	.439	.4304	(–6,032, 2,406)	(–3,223, 2,359)

Abbreviations: CI = confidence interval; PSBB = propensity score bin bootstrapping; U-100 = regular U-100 insulin (total daily dose ≥150 units); U-500R = human regular U-500 insulin.
^aDifference-in-differences refers to the difference between the pre and post periods within-subject differences of the 2 matched cohorts.
^bPerformed on the unmatched groups: U-500R, n = 1,044; U-100, n = 11,520.

Table 4. Adherence (PDCindex) Subgroup Analysis ^a
Subgroups	U-500R (n = 1,039)	U-100 (n = 1,039)
Overall	65.01%	47.63%
Age
≥65 years (n = 287)	69.90%^b	45.47%
<65 years (n = 1,791)	64.27%	47.99%
Type of Diabetes
T1D (n = 394)	65.28%	51.42%
T2D (n = 1,684)	64.95%	46.74%
Method of Insulin Delivery
MDI (n = 1,538)	65.22%	44.27%
CSII (n = 540)	64.38%	56.89%^c

Abbreviations: CSII = continuous subcutaneous insulin infusion; MDI = multiple daily injections; PDC = proportion of days covered; T1D = type 1 diabetes; T2D = type 2 diabetes; U-100 = regular U-100 insulin (total daily dose ≥150 units); U-500R = human regular U-500 insulin.
^aPDCindex refers to the proportion of days covered using the index insulin regimen for the U-100 cohort.
^b P<.05 (from analysis of variance test).
^c P<.0001 (from analysis of variance test).