Dosing of U-100 insulin and associated outcomes among Medicare enrollees with type 1 or type 2 diabetes

Figures & data

Table 1 Highest dose cohort by index dose

Variable	Dose 10–100 units/day of insulin (N=31,551)		Dose >100–150 (N=9,223)		Dose >150–200 (N=3,968)		Dose >200–300 (N=2,560)		Dose >300 (N=871)		P-value
	N or mean	% or SD	N or mean	% or SD	N or mean	% or SD	N or mean	% or SD	N or mean	% or SD
Patient characteristics
Age (mean; SD)	77.11	6.83	75.61	6.26	74.65	5.76	73.65	5.18	72.99	4.95	<0.0001
Sex											<0.0001
Female	15,286	48.45	4,247	46.05	1,669	42.06	1,025	40.04	304	34.90
Male	16,265	51.55	4,976	53.95	2,299	57.94	1,535	59.96	567	65.10
Region											<0.0001
Northeast	4,786	15.17	1,290	13.99	489	12.32	305	11.91	109	12.51
North Central	13,541	42.92	4,044	43.85	1,770	44.61	1,184	46.25	396	45.46
West	4,900	15.53	1,433	15.54	623	15.70	361	14.10	139	15.96
South	8,324	26.38	2,456	26.63	1,086	27.37	710	27.73	227	26.06
Insurance											<0.0001
HMO	4,474	14.18	998	10.82	326	8.22	189	7.38	66	7.58
POS	920	2.92	302	3.27	141	3.55	98	3.83	33	3.79
Other	17,295	54.82	5,502	59.66	2,439	61.47	1,543	60.27	521	59.82
PPO	8,862	28.09	2,421	26.25	1,062	26.76	730	28.52	251	28.82
Pre-period
Charlson score (mean; SD)	3.09	2.07	3.12	1.96	3.17	1.92	3.23	1.91	3.49	1.91	<0.0001
Diabetes classification											<0.0001
Type 1	1,288	4.08	568	6.16	228	5.75	155	6.05	35	4.02
Type 2	30,263	95.92	8,655	93.84	3,740	94.25	2,405	93.95	836	95.98
Comorbidities
Retinopathy	4,324	13.70	1,783	19.33	762	19.20	530	20.70	172	19.75	<0.0001
Nephropathy	7,576	24.01	2,198	23.83	931	23.46	605	23.63	274	31.46	<0.0001
Neuropathy	1,294	4.10	417	4.52	212	5.34	144	5.63	56	6.43	<0.0001
Coronary artery disease	12,081	38.29	3,801	41.21	1,722	43.40	1,183	46.21	431	49.48	<0.0001
Peripheral vascular disease	5,545	17.57	1,597	17.32	718	18.09	468	18.28	156	17.91	0.7228
Congestive heart failure	6,435	20.40	1,793	19.44	791	19.93	567	22.15	231	26.52	<0.0001
Hypertension	20,759	65.80	5,866	63.60	2,496	62.90	1,595	62.30	574	65.90	<0.0001
Depression	1,388	4.40	338	3.66	158	3.98	93	3.63	36	4.13	0.0159
Obesity	1,277	4.05	462	5.01	233	5.87	202	7.89	96	11.02	<0.0001
Malignancy	5,756	18.24	1,557	16.88	619	15.60	438	17.11	153	17.57	0.0001
Visit to endocrinologist	4.053	12.85	1,628	17.65	753	18.98	512	20.00	212	24.34	<0.0001

Note: Differences in distributions across dose categories were examined using chi-square statistics for categorical variables and ANOVA for continuous variables.

Abbreviations: SD, standard deviation; HMO, Health Maintenance Organization; POS, Point of Service; PPO, Preferred Provider Organization; ANOVA, analysis of variance.

Table 2 Highest dose cohort antidiabetic medication use – by insulin dosage

Variable	Dose 10–100		Dose >100–150		Dose >150–200		Dose >200–300		Dose >300–2,500		P-value
	N or mean	% or SD	N or mean	% or SD	N or mean	% or SD	N or mean	% or SD	N or mean	% or SD
Index medication											<0.0001
Basal	16,412	52.02	2,056	22.29	645	16.26	271	10.59	69	7.92
Basal + bolus	6,013	19.06	4,194	45.47	2,067	52.09	1,503	58.71	566	64.98
Basal + bolus + premix	109	0.35	125	1.36	92	2.32	75	2.93	36	4.13
Basal + premix	325	1.03	258	2.80	150	3.78	122	4.77	39	4.48
Bolus	3,863	12.24	600	6.51	192	4.84	194	4.06	35	4.02
Bolus + premix	240	0.76	182	1.97	100	2.52	87	3.40	24	2.76
Premix	4,589	14.54	1,808	19.60	722	18.20	398	15.55	102	11.71
Pre-period diabetic medication use
Basal	18,285	57.95	6,850	74.27	3,062	77.7	2,036	79.53	727	83.47	<0.0001
Bolus	7,126	22.59	5,305	57.52	2,592	65.32	1,860	72.66	688	78.99	<0.0001
Premix	4,853	15.38	2,478	26.87	1,140	28.73	755	29.49	238	27.32	<0.0001
Human	6,250	19.81	2,945	31.93	1,282	32.31	820	32.03	263	30.20	<0.0001
Analog	19,052	60.38	7,297	79.12	3,256	82.06	2,163	84.49	771	88.52	<0.0001
Pen	10,191	32.30	4,049	43.90	1,879	47.35	1,234	48.20	426	48.91	<0.0001
Vial	15,184	48.13	6,381	69.19	2,798	70.51	1,827	71.37	662	76.00	<0.0001
Pump	438	1.39	217	2.35	77	1.94	54	2.11	17	1.95	<0.0001
Insulin	23,576	74.72	9,034	97.95	3,924	98.89	2,545	99.41	868	99.66	<0.0001
Oral antidiabetic (OAD) agent	20,845	66.07	4,658	50.50	1,883	47.45	1,203	46.99	376	43.17	<0.0001
Number of OAD (mean; SD)	1.14	1.05	0.77	0.92	0.69	0.87	0.64	0.81	0.59	0.79	<0.0001
GLP-AMY	1,072	3.40	330	3.58	186	4.69	130	5.08	78	8.96	<0.0001
Diabetic medication use											<0.0001
Insulin + oral/GLP-AMY	15,307	48.52	4,639	50.30	1,921	48.41	1,249	48.79	413	47.42
Insulin only	8,269	26.21	4,395	47.65	2,003	50.48	1,296	50.63	455	52.24
None	2,288	7.25	84	0.91	27	0.68	10	0.39	3	0.34
OAD/GLP-AMY only	5,687	18.02	105	1.14	17	0.43	5	0.20	0	0.00

Note: Differences in distributions across dose categories were examined using chi-square statistics for categorical variables and ANOVA for continuous variables.

Abbreviations: ANOVA, analysis of variance; SD, standard deviation; GLP-AMY, non-insulin injectables of glucagon-like peptide-1 analogs or amylin analogs.

Table 3 Estimated direct medical costs by dose

	Dose 10–100		Dose >100–150		Dose >150–200		Dose >200–300		Dose >300–2,500		P-value
	Mean	SD	Mean	SD	Mean	SD	Mean	SD	Mean	SD
Direct medical costs
Inpatient	8,917	6,336	7,273	4,569	6,993	4,386	7,420	4,756	8,324	4,946	<0.0001
Emergency room	812	498	741	433	781	461	712	419	696	397	<0.0001
Outpatient	13,133	9,094	11,535	7,018	11,862	7,181	12,877	7,826	13,691	7,624	<0.0001
Drug	5,845	1,328	7,536	1,632	8,980	1,927	10,622	2,224	14,645	3,072	<0.0001
Total	28,571	15,102	27,133	12,348	28,794	13,175	31,977	14,580	38,301	16,169	<0.0001
Direct diabetes-related medical costs
Inpatient	2,251	2,085	1,904	1,814	1,936	1,890	1,930	1,911	2,053	2,058	<0.0001
Emergency room	271	175	265	168	267	176	245	158	266	168	<0.0001
Outpatient	2,357	1,301	2,380	1,239	2,657	1,450	2,505	1,362	2,957	1,471	<0.0001
Drug	1,707	628	2,963	940	4,015	1,298	5,390	1,676	8,389	2,708	<0.0001
Total	6,562	2,682	7,473	2,990	8,910	3,604	10,065	4,086	13,961	5,551	<0.0001

Notes: Differences in outpatient drug and total costs (both total and diabetes-related) were examined using a generalized linear model with gamma distribution and log link. Differences in inpatient and emergency room costs (both total and diabetes-related) were examined using a two-part model where the first part estimated the probability of utilizing the resource of interest and the second part examined costs among those who utilized the resource of interest. All regressions controlled for patient characteristics (age, sex, region, insurance status), general health (as proxied by the Charlson Comorbidity Index), pre-period comorbidities (retinopathy, neuropathy, nephropathy, coronary artery disease, peripheral vascular disease, congestive heart failure, hypertension, depression, obesity, and malignancies), pre-period antidiabetic medication use (oral, insulin, or non-insulin injectable) and method of insulin delivery (pump or vial), type of diabetes, and whether the individual visited an endocrinologist in the pre-period.

Abbreviation: SD, standard deviation.

Table 4 Resource utilization and index dose

Resource utilization	Dose 10–100		Dose >100–150		Dose >150–200		Dose >200–300		Dose >300–2,500		P-value
	Mean	SD	Mean	SD	Mean	SD	Mean	SD	Mean	SD
All patients
Hospital length of stay (LOS)	3.87	3.14	3.04	1.89	3.09	1.90	3.30	1.99	3.62	2.03	<0.0001
Number of hospitalizations	0.56	0.32	0.48	0.22	0.49	0.23	0.50	0.23	0.56	0.25	<0.0001
Number of ER visits	1.21	0.73	1.08	0.56	1.13	0.57	1.08	0.54	1.14	0.55	<0.0001
Number of office visits	15.76	4.96	16.86	5.25	18.06	5.73	19.05	5.82	19.93	5.67	<0.0001
Diabetes-related hospital LOS	1.80	1.43	1.47	0.88	1.55	0.95	1.68	0.97	1.77	0.96	<0.0001
Number of diabetes-related Hosp	0.28	0.18	0.25	0.13	0.26	0.13	0.26	0.13	0.28	0.13	<0.0001
Users of resource only
Hospital LOS	9.91	2.80	9.03	2.24	8.73	2.15	9.15	2.23	9.66	2.24	<0.0001
Number of hospitalizations	1.46	0.26	1.42	0.23	1.41	0.22	1.42	0.20	1.47	0.21	<0.0001
Number of ER visits	2.48	0.56	2.39	0.50	2.47	0.51	2.35	0.49	2.41	0.48	<0.0001
Diabetes-related hospital LOS	8.17	2.01	7.75	1.69	7.59	160	7.95	1.60	8.92	1.92	<0.0001
Number of diabetes-related Hosp	1.28	0.20	1.30	0.19	1.26	0.17	1.27	0.16	1.31	0.17	<0.0001

Notes: Differences in all resource utilization models were examined using generalized linear model with a negative binomial distribution. All regressions controlled for patient characteristics (age, sex, region, insurance status), general health (as proxied by the Charlson Comorbidity Index), pre-period comorbidities (retinopathy, neuropathy, nephropathy, coronary artery disease, peripheral vascular disease, congestive heart failure, hypertension, depression, obesity, and malignancies), pre-period antidiabetic medication use (oral, insulin, or non-insulin injectables) and method of insulin delivery (pump or vial), type of diabetes, and whether the individual visited an endocrinologist in the pre-period.

Abbreviations: SD, standard deviation; ER, emergency room; LOS, length of stay; Hosp, hospitalizations.

Figure 1 Probability of PDC ≥80% (odds ratios and 95% CIs).

Abbreviations: PDC, proportion of days covered; CIs, confidence intervals.

Figure 2 Probability of hypoglycemic event (odds ratios and 95% CIs).

Abbreviation: CIs, confidence intervals.