Hospitalization costs with degludec versus glargine U100 for patients with type 2 diabetes at high cardiovascular risk: Canadian costs applied to SAEs from a randomized outcomes trial

Figures & data

Figure 1. Study flow of Canadian hospital abstracts. ^†ICD-10-CA diagnosis code listed as type “most responsible diagnosis”, “pre-admit comorbidity” or “post-admit comorbidity” (DAD); or as type “main problem” or “other problem” (NACRS). Abbreviations. CSHS, cost of a standard hospital stay; DAD, Discharge Abstract Database; ED, emergency department; ICD-10-CA, ICD-10-CA, International Statistical Classification of Diseases and Related Health Problems, 10^th Revision, Canada; n, number of hospital abstracts; NACRS, National Ambulatory Care Reporting System; RIW, resource intensity weight.

Table 1. Annual hospitalization costs with degludec and glargine U100.

	Mean annual cost per patient† (CAD)			95% CI of cost difference	P-value for cost difference	Cost ratio	95% CI of cost ratio	P-value for cost ratio
	Degludec	Glargine U100	Difference
Main analysis
Unit costs: weighted^‡ average across acute inpatient and ED settings	4,074	4,569	–495	–966;–24	.039	0.89	0.81;0.98	.016
Sensitivity analyses
1. Without substitution of missing preferred term unit costs	3,911	4,379	–468	–926;–10	.045	0.89	0.81;0.98	.021
2. Unit costs: acute inpatient setting only	7,505	8,372	–867	–1,658;–75	.032	0.90	0.83;0.97	.010
3. Unit costs: sum of acute inpatient and ED settings	7,723	8,617	–895	–1,694;–96	.028	0.90	0.83;0.97	.009
4. Unit costs: weighted average across acute inpatient, day surgery, and ED settings	3,772	4,256	–484	–928;–40	.033	0.89	0.81;0.98	.014

The cost difference, 95% CIs, and p-values were based on non-parametric bootstrapping, while the cost ratio (degludec/glargine U100), 95% CIs, and p-values were based on a Tweedie distribution in SAS GENMOD, n = 7,637.

^†Observed means weighted by exposure in DEVOTE, with the difference reported for degludec minus glargine U100.

^‡Weighted average was calculated as follows: (1) acute inpatient-weight = #acute inpatient-abstracts/(#acute inpatient-abstracts + #ED-abstracts) where the #abstracts is the projected #abstracts; (2) the ED weight was calculated similarly to (1); (3) weighted average cost = acute inpatient-weight*acute inpatient-unit cost + ED-weight*ED-unit cost.

Abbreviations. CAD, Canadian dollar; CI, confidence interval; ED, emergency department; glargine U100, insulin glargine 100 units/mL.

Table 2. Aggregate hospitalization costs by SOC.

SOC	SAE rate (events per 100 patient-years)		Rate ratio	Mean annual cost per patient^† (CAD)		Cost ratio	Cost difference (CAD)	Relative distribution^‡ (%)
	Degludec	Glargine U100		Degludec	Glargine U100
Cardiac disorders	11.55	12.86	0.90	1,287	1,413	0.91	–126	25.5
Nervous system disorders	3.70	4.54	0.82	303	399	0.76	–96	19.3
Renal and urinary disorders	2.26	2.78	0.81	283	369	0.77	–86	17.3
Blood and lymphatic system disorders	0.41	0.90	0.46	55	116	0.47	–61	12.3
Respiratory, thoracic, and mediastinal disorders	2.56	3.19	0.80	401	461	0.87	–60	12.2
Vascular disorders	1.76	2.26	0.78	168	220	0.76	–52	10.5
Infections and infestations	6.62	7.26	0.91	639	689	0.93	–50	10.1
Gastrointestinal disorders	2.35	2.46	0.96	151	170	0.89	–19	3.8
General disorders and administration-site conditions	1.72	2.09	0.82	46	63	0.72	–18	3.5
Psychiatric disorders	0.56	0.61	0.91	36	43	0.84	–7	1.4
Congenital, familial, and genetic disorders	0.01	0.11	0.12	1	6	0.13	–5	1.1
Product issues	0.08	0.12	0.67	4	6	0.67	–2	0.4
Investigations	0.21	0.22	0.94	6	8	0.76	–2	0.4
Surgical and medical procedures	0.53	0.57	0.93	15	16	0.90	–2	0.3
Social circumstances	0.01	0.00	N/A	0	0	N/A	0	–0.1
Hepatobiliary disorders	0.53	0.50	1.05	33	32	1.02	1	–0.1
Immune system disorders	0.04	0.04	1.00	1	0	3.78	1	–0.1
Ear and labyrinth disorders	0.12	0.11	1.12	3	1	3.44	2	–0.4
Endocrine disorders	0.08	0.04	2.00	6	3	2.31	3	–0.7
Neoplasms benign, malignant, and unspecified (including cysts and polyps)	1.52	1.57	0.97	100	95	1.05	4	–0.9
Reproductive system and breast disorders	0.29	0.19	1.57	14	9	1.56	5	–1.0
Metabolism and nutrition disorders	2.42	2.42	1.00	249	241	1.03	8	–1.6
Musculoskeletal and connective tissue disorders	1.77	1.77	1.00	98	84	1.16	13	–2.7
Skin and subcutaneous tissue disorders	0.53	0.44	1.21	55	39	1.39	15	–3.1
Eye disorders	0.33	0.22	1.47	29	12	2.38	17	–3.3
Injury, poisoning, and procedural complications	2.19	2.28	0.96	93	72	1.28	20	–4.1
Total	44.1	49.6	0.89	4,074	4,569	0.89	–495	100.0

Reported using the Medical Dictionary for Regulatory Activities version 21.0. Cost ratios and rate ratios were reported for degludec/glargine U100.

^†Observed means weighted by exposure in DEVOTE, with the difference reported for degludec minus glargine U100.

^‡Relative to the total cost difference (CAD –495.1).

Abbreviations. CAD, Canadian dollar; glargine U100, insulin glargine 100 units/mL; SAE, serious adverse event; SOC, system organ class.

Table 3. Top 10 single preferred term drivers and annual hospitalization costs with degludec and glargine U100.

Rank	Preferred term	System organ class	Mean SAE rate (events per 100 patient-years)			Unit hospitalization cost estimate (CAD)	Mean annual cost per patient^† (CAD)
			Degludec	Glargine U100	Rate ratio		Degludec	Glargine U100	Difference
1	Acute kidney injury	Renal and urinary disorders	1.07	1.48	0.72	15,523	166	230	−64
2	Anaemia	Blood and lymphatic system disorders	0.16	0.53	0.30	12,398	20	66	−46
3	Acute respiratory failure	Respiratory, thoracic, and mediastinal disorders	0.34	0.46	0.74	34,843	120	161	−42
4	Cardiac failure congestive	Cardiac disorders	2.23	2.61	0.86	10,096	225	263	−38
5	Cerebrovascular accident	Nervous system disorders	0.15	0.30	0.48	21,794	32	66	−35
6	Atrial fibrillation	Cardiac disorders	0.73	0.99	0.73	10,539	77	105	−28
7	Myocardial infarction	Cardiac disorders	0.67	0.90	0.75	10,496	71	94	−24
8	Chronic kidney disease	Renal and urinary disorders	0.24	0.40	0.60	14,107	34	56	−22
9	Skin ulcer	Skin and subcutaneous tissue disorders	0.17	0.07	2.60	20,178	35	13	21
10	Angina pectoris	Cardiac disorders	0.49	0.70	0.70	9,396	46	66	−20

Reported using the Medical Dictionary for Regulatory Activities version 21.0 and ranked from largest to smallest difference in a mean annual cost per patient. Cost ratios and rate ratios were reported for degludec/glargine U100.

^†Observed means weighted by exposure in DEVOTE, with the difference reported for degludec minus glargine U100.

Abbreviations. CAD, Canadian dollar; glargine U100, insulin glargine 100 units/mL; SAE, serious adverse event.

Data availability statement

All estimates for unit hospitalization costs are available in the appendices, while the SAE data from DEVOTE are publicly available at ClinicalTrials.gov or in the DEVOTE primary publication. The DEVOTE clinical trial report is available from the corresponding author on request. The raw CIHI data include some personal health information and will not be made publicly available.