Real-world rates, predictors, and associated costs of hypoglycemia among patients with type 2 diabetes mellitus treated with insulin glargine: results of a pooled analysis of six retrospective observational studies

Figures & data

Table 1. Baseline demographics and clinical characteristics.

	GLA-P (n = 14,911)	GLA-V (n = 8187)	p-value for between-group comparison	All GLA-treated patients (n = 23,098)
Age at year of index date, years, mean (SD)	53.9 (9.3)	54.5 (9.8)	<0.0001	54.1 (9.5)
Female, n (%)	6993 (46.8)	3757 (45.8)	0.1416	10,750 (46.5)
HbA1c,* mean % (SD)	9.37 (1.96)	9.27 (2.09)	0.2583	9.34 (2.00)
Comorbidities
CCI, mean (SD)	0.51 (1.18)	0.62 (1.30)	<0.0001	0.55 (1.23)
Hypertension, n (%)	7031 (47.1)	4277 (52.2)	<0.0001	11,308 (48.9)
Hyperlipidemia, n (%)	6859 (45.9)	3949 (48.2)	0.0011	10,808 (46.7)
Mental illness, n (%)	1503 (10.0)	1012 (12.3)	<0.0001	2515 (10.8)
Neuropathy, n (%)	1249 (8.3)	757 (9.2)	0.0247	2006 (8.6)
Retinopathy, n (%)	1009 (6.7)	642 (7.8)	0.0024	1651 (7.1)
Nephropathy, n (%)	564 (3.7)	334 (4.0)	0.2637	898 (3.8)
Anti-diabetes drugs
Number of OADs, mean (SD)	2.48 (1.18)	2.39 (1.16)	<0.0001	2.45 (1.17)
Metformin, n (%)	12,073 (80.9)	6503 (79.4)	0.0049	18,576 (80.4)
Sulfonylureas, n (%)	10,034 (67.2)	5532 (67.5)	0.6664	15,566 (67.3)
Thiazolidinediones, n (%)	5945 (39.8)	3181 (38.8)	0.1310	9126 (39.5)
Sitagliptin, n (%)	3128 (20.9)	1424 (17.3)	<0.0001	4552 (19.7)
Exenatide, n (%)	2723 (18.2)	1204 (14.7)	<0.0001	3927 (17.0)
Healthcare utilization, n (%)
Any hospitalization	2067 (13.8)	1556 (19.0)	<0.0001	3623 (15.6)
Any ED visit	1538 (10.3)	1101 (13.4)	<0.0001	2639 (11.4)
Any office visit	9515 (63.8)	7990 (97.5)	<0.0001	17,505 (75.7)
Any endocrinologist visit	2334 (15.6)	750 (9.1)	<0.0001	3084 (13.3)
Hypoglycemia, n (%)
Any hypoglycemia	489 (3.2)	343 (4.1)	0.0004	832 (3.6)
Any inpatient/ED hypoglycemia	154 (1.9)	133 (1.6)	0.0001	287 (1.2)
# of Hypoglycemia, mean (SD)
Any hypoglycemia	0.08 (0.98)	0.11 (0.98)	0.0416	0.09 (0.98)
Inpatient/ED hypoglycemia	0.01 (0.11)	0.02 (0.15)	<0.0001	0.02 (0.12)
Costs, $, mean (SD)
Total costs	9612 (27,260)	12,168 (31,932)	<0.0001	10,518 (29,027)
Diabetes-related total costs	3812 (12,777)	4853 (15,136)	<0.0001	4181 (13,669)
Total hypoglycemia claim-related costs	152 (2621)	247 (4456)	0.0773	186 (3388)

*HbA1c data were available from 2554 patients (GLA-P, n = 1812; GLA-V, n = 742).

CCI, Charlson comorbidity index; ED, emergency department; GLA, insulin glargine; GLA-P, insulin glargine with disposable pen; GLA-V, insulin glargine with vial-and-syringe; OAD, oral anti-diabetic drug; SD, standard deviation.

Figure 1. Annual prevalence rate (a) and event rate (b) of hypoglycemia. *p < 0.0001 for GLA-P vs GLA-V. ED, emergency department; GLA, insulin glargine; GLA-P, insulin glargine with disposable pen; GLA-V, insulin glargine with vial and syringe.

Figure 2. Associated absolute (a) and relative costs (b) of hypoglycemia. (a) Data are presented as costs associated with any hypoglycemia or inpatient/ED hypoglycemia. (b) Data are presented as percentage of total costs or of diabetes-related costs. p-values for between-group comparison GLA-P vs GLA-V: *p = 0.001; ^†p = 0.02; ^‡p < 0.0001; ^$p = 0.0003. ED, emergency department; GLA, insulin glargine; GLA-P, insulin glargine with disposable pen; GLA-V, insulin glargine with vial-and-syringe.

Table 2. Logistic regression model for predictors of hypoglycemia.

Parameter	Any hypoglycemia		Inpatient/ED hypoglycemia
	OR (95% CI)	p-value	OR (95% CI)	p-value
Age	1.00 (1.00, 1.01)	0.2245	1.00 (0.99, 1.01)	0.6126
Female	0.92 (0.83, 1.03)	0.1643	0.87 (0.73, 1.05)	0.1477
Group: GLA-P vs GLA-V	0.74 (0.66, 0.83)	<0.0001	0.73 (0.65, 0.81)	<0.0001
Baseline hypoglycemia
Any inpatient/ED hypoglycemia vs. no hypoglycemia	6.55 (5.03, 8.53)	<0.0001	10.08 (7.34, 13.83)	<0.0001
Outpatient hypoglycemia vs. no hypoglycemia	7.65 (6.30, 9.29)	<0.0001	2.86 (2.00, 4.10)	<0.0001
Comorbidity
CCI	1.08 (1.04, 1.13)	<0.0001	1.10 (1.04, 1.17)	0.0011
Hypertension	1.05 (0.94, 1.19)	0.3857	0.98 (0.81, 1.19)	0.8541
Hyperlipidemia	0.98 (0.87, 1.10)	0.7460	0.85 (0.71, 1.03)	0.1028
Retinopathy	1.20 (0.99, 1.45)	0.0602	1.22 (0.90, 1.65)	0.2041
Neuropathy	2.26 (1.95, 2.62)	<0.0001	2.43 (1.94, 3.05)	<0.0001
Nephropathy	1.26 (0.99, 1.59)	0.0606	1.54 (1.09, 2.18)	0.0143
Severe mental illness	1.31 (1.03, 1.67)	0.0272	1.36 (0.94, 1.97)	0.1082
Anti-diabetes drugs
Metformin	0.86 (0.75, 0.99)	0.0307	0.82 (0.66, 1.01)	0.0633
Sulfonylureas	1.09 (0.97, 1.24)	0.1501	1.00 (0.82, 1.21)	0.9846
Thiazolidinediones	0.98 (0.88, 1.10)	0.7601	0.91 (0.76, 1.10)	0.3369
Sitagliptin	1.00 (0.87, 1.15)	0.9959	1.01 (0.80, 1.27)	0.9650
Exenatide	0.86 (0.73, 1.00)	0.0553	0.79 (0.61, 1.03)	0.0859

CCI, Charlson comorbidity index; CI, confidence interval; OR, adjusted odds ratio; GLA-P, insulin glargine with disposable pen; GLA-V, insulin glargine with vial and syringe. The model controlled for health plan type, baseline use of meglitinides, and alpha-glucosidase.

Table 3. Negative binomial regression model of numbers of hypoglycemic events.

Parameter	Any hypoglycemia		Inpatient/ED hypoglycemia
	Estimate (95% CI)	p-value	Estimate (95% CI)	p-value
Age	0.00 (−0.01, 0.00)	0.3293	0.00 (−0.01, 0.01)	0.6578
Female	−0.30 (−0.46, −0.15)	0.0001	−0.14 (−0.37, 0.08)	0.2032
Group: GLA-P vs GLA-V	−0.44 (−0.60, −0.28)	<0.0001	−0.73 (−0.95, −0.51)	<0.0001
Baseline hypoglycemia
Any inpatient/ED hypoglycemia vs. no hypoglycemia	1.98 (1.37, 2.59)	<0.0001	2.01 (1.31, 2.71)	<0.0001
Outpatient hypoglycemia vs. no hypoglycemia	2.35 (1.91, 2.80)	<0.0001	0.33 (−0.29, 0.94)	0.2964
Comorbidity
CCI	0.22 (0.15, 0.29)	<0.0001	0.17 (0.08, 0.27)	0.0003
Hypertension	0.19 (0.03, 0.36)	0.0178	0.19 (−0.03, 0.42)	0.0902
Hyperlipidemia	0.00 (−0.16, 0.16)	0.9928	−0.20 (−0.42, 0.03)	0.0872
Retinopathy	0.49 (0.20, 0.77)	0.0008	0.55 (0.18, 0.92)	0.0035
Neuropathy	1.01 (0.76, 1.27)	<0.0001	0.91 (0.58, 1.24)	<0.0001
Nephropathy	−0.18 (−0.56, 0.21)	0.3694	0.17 (−0.33, 0.67)	0.5122
Severe mental illness	0.12 (−0.25, 0.50)	0.5208	0.22 (−0.30, 0.73)	0.4059
Anti-diabetes drugs
Metformin	−0.37 (−0.56, −0.18)	0.0002	−0.52 (−0.78, −0.25)	0.0001
Sulfonylureas	0.24 (0.07, 0.40)	0.0047	−0.01 (−0.24, 0.22)	0.9431
Thiazolidinediones	−0.01 (−0.16, 0.15)	0.9407	0.04 (−0.19, 0.26)	0.7338
Sitagliptin	−0.03 (−0.22, 0.16)	0.7806	0.07 (−0.20, 0.35)	0.5988
Exenatide	−0.36 (−0.57, −0.15)	0.0007	−0.30 (−0.61, 0.00)	0.0494

CCI, Charlson comorbidity index; CI, confidence interval; GLA-P, insulin glargine with disposable pen; GLA-V, insulin glargine with vial and syringe. The model controlled for health plan type, baseline use of meglitinides, and alpha-glucosidase.