Comparison of utilization, cost, adherence, and hypoglycemia in patients with type 2 diabetes initiating rapid-acting insulin analog with prefilled pen versus vial/syringe

Figures & data

Table 1.  Patient characteristics before and after propensity score matching.

	Before propensity score matching			After propensity score matching
	KwikPen	Vial/syringe	p-value*	KwikPen	Vial/syringe	p-value*
Sample size (n)	268	3,820		239	590
Mean age (years)	58	62	<0.001	59	60	0.224
Gender (%)
Male	52.2	51.2	0.731	53.1	51.5	0.674
Female	47.8	48.8	0.731	46.9	48.5	0.674
Geographic region (%)
Northeast	10.4	7.2	0.048	10.0	9.2	0.691
North central	40.3	32.6	0.010	40.6	40.8	0.945
South	37.3	39.3	0.516	38.1	39.5	0.705
West	11.9	20.9	0.000	11.3	10.5	0.740
Population density (%)
Rural	16.0	18.4	0.339	16.3	16.4	0.966
Urban	84.0	81.6	0.339	83.7	83.6	0.966
Provider type associated with the index RAIA (%)
Primary care physician	46.3	38.5	0.011	47.7	48.6	0.805
Endocrinologists	22.0	5.9	<0.001	18.8	19.3	0.870
Other	31.7	55.6	<0.001	33.5	32.0	0.870
Time of index RAIA (%)
First quarter of 2008	28.0	50.8	<0.001	30.1	29.8	0.933
Second quarter of 2008	72.0	49.2	<0.001	69.9	70.2	0.933
Insurance plan source (%)
Commercial	72.0	57.8	<0.001	70.3	66.8	0.327
Medicare^†	28.0	42.2	<0.001	29.7	33.2	0.327
Insurance plan type (%)
Indemnity plan	18.7	20.8	0.411	47	20.0	0.913
Other	81.3	79.2	0.411	192	80.0	0.913
Copayment amount ($, mean)
Insulin	27.0	22.1	0.000	26.9	26.7	0.880
OHAs	15.6	13.7	0.032	15.3	14.8	0.683
CCI (mean)	2.1	2.2	0.295	2.1	2.2	0.520
Diabetes-related complications^‡ (%)
Neuropathy	17.2	22.1	0.060	17.2	18.5	0.655
Nephropathy	14.9	18.1	0.195	15.5	16.8	0.648
Retinopathy	8.2	10.7	0.202	8.4	8.1	0.912
Ischemic heart diseases	18.7	21.7	0.237	18.8	19.7	0.784
Cerebrovascular diseases	5.6	10.7	0.008	6.3	6.4	0.930
Congestive heart failure	4.9	12.4	0.000	5.4	5.1	0.835
Peripheral vascular diseases	5.2	9.0	0.035	5.4	6.9	0.425
Comorbidities^‡ (%)
Hypertension	30.6	36.5	0.052	30.5	31.0	0.894
Disorders of lipid metabolism	27.6	20.2	0.004	25.5	23.9	0.622
Obesity	1.9	2.2	0.698	2.1	2.7	0.607
Depression	3.4	6.6	0.035	3.3	3.1	0.825
Diseases of esophagus, stomach, and duodenum	7.1	7.0	0.977	6.3	9.5	0.134
Dexterity-impacting diseases	6.0	9.4	0.059	5.4	5.9	0.783
Pre-index insulin use^§ (%)
Insulin naive	29.5	39.1	0.002	33.1	38.5	0.143
Basal pen	32.1	3.3	<0.001	25.5	15.8	0.001
Basal vial	27.2	41.8	<0.001	29.7	33.1	0.350
Other pen	9.0	1.2	<0.001	6.7	4.6	0.213
Other vial	11.9	21.4	0.000	13.4	16.1	0.326
Use of insulin: analog versus human (%)
Analog	63.8	48.2	<0.001	59.8	52.9	0.069
Human	10.4	17.4	0.004	10.9	12.2	0.593
Use of OHAs (%)
No OHAs	23.5	44.5	<0.001	25.1	25.3	0.964
1 OHA	26.9	29.0	0.455	28.5	30.3	0.591
>1 OHAs	49.6	26.5	<0.001	46.4	44.4	0.593
Use of exenatide/pramlintide (%)	14.2	5.6	<0.001	12.1	11.0	0.646
Use of SMBG (%)	30.2	28.9	0.638	29.7	25.9	0.268
Adherence to AHTs and SMBG^¶ (%)
PDC <50%	45.5	58.1	<0.001	46.0	44.6	0.704
PDC ≥50% and <80%	41.0	31.2	0.001	40.6	39.7	0.806
PDC ≥80%	13.4	10.7	0.162	13.4	15.8	0.387

*T-test was used for continuous variables and chi-squared test was used for categorical variables.

^†Indicates Medicare Supplemental Plan only. Information on basic Medicare plan is not included.

^‡ICD-9-CM and CPT codes were used to identify diabetes-related complications and comorbidities.

^§The variable, ‘pre-index insulin use’ was categorized as: ‘insulin naive’ if a patient did not have any pharmacy claims of insulin therapy, ‘basal pen’ if a patient used long-acting insulin (e.g., insulin glargine) with a pen, ‘basal vial’ if a patient used long-acting insulin with vial/syringe, ‘other pen’ if a patient used any other insulin (e.g., premixed insulin) with a pen, or ‘other vial’ if a patient used any other insulin with vial/syringe.

^¶AHTs are inclusive of OHAs (metformin, sulfonylureas (SUs), thiazolidinediones (TZDs), alpha-glucosidase inhibitors (AGIs), non-SU secretagogues, dipeptidyl peptidase-4 (DPP-4) inhibitors), insulin, and exenatide/pramlintide.

OHAs, oral antihyperglycemic agents; RAIA, rapid-acting insulin analog; CCI, Charlson Comorbidity Index; SMBG, self-monitoring blood glucose; AHTs, anti-hyperglycemic agents; PDC, proportion of days covered.

Figure 1.  Study sample flow diagram.

Table 2.  Results of adherence and difference-in-difference (DID) analysis on resource utilization and hypoglycemia rate.

	Pre-index			Post-index			Difference from pre-index to post-index^†
	KwikPen (n = 239)	Vial/syringe (n = 590)	p-value*	KwikPen (n = 239)	Vial/syringe (n = 590)	p-value*	KwikPen (n = 239)	Vial/syringe (n = 590)	p-value*	DID^‡
	[A]	[B]		[C]	[D]		[E] = [C] – [A]	[F] = [D] – [B]		[G] = [F] – [E]
Pharmacy utilization (count, mean)
OHAs	3.4	3.4	0.896	2.2	2.7	0.021	–1.3	–0.7	0.016	0.6
All AHTs and SMBG	6.0	5.9	0.824	8.3	8.3	0.936	2.3	2.4	0.731	0.1
Other drugs of interest^§	6.8	6.9	0.907	7.4	7.6	0.734	0.6	0.7	0.721	0.1
Diabetes-related medical utilization  (count, mean)
Outpatient service	3.5	3.6	0.649	3.5	3.5	0.946	0.0	–0.1	0.717	–0.1
Inpatient admission	0.1	0.1	0.324	0.1	0.1	0.624	–0.0	–0.0	0.602	–0.0
Emergency room visits	0.1	0.1	0.845	0.1	0.1	0.245	0.1	0.0	0.312	–0.0
Total medical utilization  (count, mean)
Outpatient service	14.1	15.5	0.300	15.4	17.6	0.148	1.3	2.1	0.459	0.8
Inpatient admission	0.2	0.3	0.214	0.2	0.2	0.586	–0.1	–0.1	0.507	–0.0
Emergency room visits	0.4	0.4	0.580	0.4	0.5	0.517	0.0	0.0	0.900	0.0
HbA1c tests (count, mean)	0.9	0.9	0.262	0.7	0.7	0.679	–0.2	–0.1	0.461	0.1
Hypoglycemia rate  (episodes per patient over 6 months)	0.03	0.03	0.905	0.03	0.02	0.539	0.004	–0.003	0.707	–0.01
Adherence to index RAIA	—	—	—	54.6%	45.2%	<0.001	—	—	—	—

*T-test was used to compare the difference.

^†Negative value indicates reduction in outcomes. Positive value indicates increase in outcomes.

^‡DID = (difference from pre- to post-index in the vial/syringe cohort) – (difference from pre- to post-index in the KwikPen cohort). Values are rounded after subtraction.

^§Inclusive of diuretics, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta blockers, calcium-channel blockers, anticoagulants, antiplatelets, and statins.

OHAs (oral antihyperglycemic agents), AHTs (antihyperglycemic agents; inclusive of OHAs, insulin, and exenatide/pramlintide), and SMBG (self-monitoring blood glucose).

Table 3.  Results of difference-in-difference (DID) analysis on cost.

	Pre-index			Post-index			Difference from pre-index to post-index^†
	KwikPen (n = 239)	Vial/syringe (n = 590)	p-value*	KwikPen (n = 239)	Vial/syringe (n = 590)	p-value*	KwikPen (n = 239)	Vial/syringe (n = 590)	p-value*	DID^‡
	[A]	[B]		[C]	[D]		[E] = [C] – [A]	[F] = [D] – [B]		[G] = [F] – [E]
Diabetes-related costs ($, mean)
Pharmacy costs	963	880	0.203	1,864	1,486	<0.001	900	607	<0.001	–294
Outpatient costs	1,095	1,054	0.504	501	751	0.457	–594	–304	0.196	290
Inpatient costs	931	919	0.455	355	685	0.284	–576	–235	0.796	341
Emergency room costs	60	60	0.995	94	53	0.187	34	–7	0.120	–41
Total diabetes-related costs	3,049	2,914	0.623	2,814	2,975	0.008	–235	61	0.006	297
Total costs ($, mean)
Pharmacy costs	2,867	2,870	0.146	4,038	3,745	0.018	1,171	874	0.058	–297
Outpatient costs	5,023	5,150	0.787	4,836	5,440	0.112	–187	290	0.791	477
Inpatient costs	4,543	5,505	0.359	2,535	2,539	0.078	–2,008	–2,967	0.579	–958
Emergency room costs	220	230	0.849	297	230	0.551	77	0	0.828	–77
Total direct costs	12,652	13,755	0.500	11,706	11,954	0.461	–946	–1,802	0.814	–855

*Wilcoxon rank-sum test was used to compare the difference.

^†Negative value indicates reduction in costs. Positive value indicates increase in costs.

^‡DID = (difference from pre- to post-index in the vial/syringe cohort) – (difference from pre- to post-index in the KwikPen cohort). Values are rounded after subtraction.

Table 4.  Results of post hoc analyses on diabetes-related pharmacy, outpatient, and inpatient cost breakdowns.

Diabetes-related costs ($, mean)	Pre-index			Post-index			Difference from pre-index to post-index^†
	KwikPen (n = 239)	Vial/syringe (n = 590)	p-value*	KwikPen (n = 239)	Vial/syringe (n = 590)	p-value*	Kwiken (n = 239)	Vial/syringe (n = 590)	p-value*	DID^‡
	[A]	[B]		[C]	[D]		[E] = [C] – [A]	[F] = [D] – [B]		[G] = [F]–[E]
Pharmacy costs	963	880	0.203	1,864	1,486	<0.001	900	607	<0.001	–294
OHAs	414	358	0.373	262	298	0.172	–152	–60	0.006	92
Metformin	45	38	0.946	40	37	0.767	–5	–1	0.983	4
SU	38	29	0.113	16	22	0.025	–22	–7	0.003	15
TZD	161	173	0.589	105	142	0.324	–56	–32	0.404	24
Inhibitor DPP-4	96	53	0.002	43	43	0.451	–53	–10	0.008	43
Other single OHA	29	28	0.513	4	21	0.118	–25	–8	0.058	17
Fixed-dose combination	44	36	0.265	53	33	0.855	9	–3	0.709	–12
Insulin	379	356	0.328	1,362	999	<0.001	982	643	<0.001	–339
Long-acting analog	259	241	0.354	634	442	<0.001	375	201	<0.001	–173
NPH	12	21	0.075	9	23	0.002	–3	2	0.055	5
RAIA	1	1	0.866	671	439	<0.001	669	438	<0.001	–232
SAHI	10	3	0.012	0	3	0.070	–9	0	0.002	10
Premixed analog	77	72	0.828	46	84	0.231	–31	12	0.058	43
Premixed human	20	18	0.897	2	8	0.181	–18	–10	0.352	8
Exenatide/pramlintide	91	93	0.661	71	76	0.619	–20	–17	0.902	3
SMBG	79	73	0.308	170	114	0.001	91	41	0.004	–50
Outpatient costs	1,095	1,054	0.504	501	751	0.457	–594	–304	0.196	290
Health care provider costs	221	212	0.415	205	212	0.633	–15	0	0.392	15
Primary care physician^§	136	132	0.594	113	130	0.103	–23	–1	0.008	22
Endocrinologist	71	63	0.777	70	55	0.181	0	–7	0.446	–7
Cardiologist	2	3	0.877	2	3	0.732	0	1	0.415	0
Others^¶	12	15	0.778	181	359	0.415	8	8	0.816	0
Facility costs**	731	673	0.183	172	310	0.522	–550	–314	0.045	236
Others	143	169	0.307	114	179	0.274	–29	10	0.488	39
Inpatient costs	931	919	0.455	355	685	0.284	–576	–235	0.796	341
Microvascular complication related	1	57	0.303	0	80	0.091	–1	23	0.940	24
Macrovascular complication related	508	117	0.996	171	244	0.648	–336	127	0.512	463
Others	422	745	0.428	184	361	0.534	–238	–384	0.557	–146

*Wilcoxon rank-sum test was used to compare the difference.

^†Negative value indicates reduction in costs. Positive value indicates increase in costs.

^‡DID = (difference from pre- to post-index in the vial/syringe cohort) – (difference from pre- to post-index in the KwikPen cohort). Values are rounded after subtraction.

^§Inclusive of physician assistant and nurse practitioner costs.

^¶Inclusive of ophthalmologist, podiatrist, diabetes educator and dietitian costs.

**Inclusive of ambulatory surgery center, rehabilitation facilities, intermediate care, etc.

SUs, sulfonylureas; TZDs, thiazolidinediones; DPP-4, dipeptidyl peptidase-4 inhibitors; NPH, neutral protamine Hagedorn; SAHI, short-acting human insulin.