Long-term cost-effectiveness analysis shows that IDegLira is associated with improved outcomes and lower costs compared with insulin glargine U100 plus insulin aspart in the US

Figures & data

Table 1. Baseline cohort characteristics.

	IDegLira, mean (SD)	Insulin glargine U100 plus insulin aspart, mean (SD)	Total, mean (SD)
Start age (years)	58.6 (9.0)	58.0 (8.6)	58.3 (8.8)
Duration of diabetes (years)	13.2 (7.0)	13.3 (6.8)	13.2 (6.9)
Percentage male (%)	43.7	46.1	44.9
HbA1c (%)	8.2 (0.8)	8.2 (0.8)	8.2 (0.8)
Systolic blood pressure (mmHg)	131.3 (13.1)	132.2 (13.7)	131.8 (13.4)
Total cholesterol (mg/dL)	176.5 (46.0)	170.7 (41.8)	173.6 (44.0)
HDL cholesterol (mg/dL)	46.9 (13.3)	46.3 (12.1)	46.6 (12.7)
LDL cholesterol (mg/dL)	95.5 (35.9)	93.3 (34.6)	94.4 (35.2)
Triglycerides (mg/dL)	180.1 (203.5)	161.1 (100.64)	170.6 (160.7)
BMI (kg/m^2)	31.7 (4.4)	31.7 (4.5)	31.7 (4.4)

Abbreviations. BMI, body mass index; HbA1c, glycated hemoglobin; HDL, high density lipoprotein; LDL, low density lipoprotein; SD, standard deviation.

A weighted average of the two treatment arms presented in Billings et al.¹² was used in the present analysis.

Table 2. Treatment effects applied in the first year of the analysis.

	IDegLira, mean (SD)	Insulin glargine U100 plus insulin aspart, mean (SD)
HbA1c (%)	−1.48 (0.78)	−1.46 (0.78)
Systolic blood pressure (mmHg)	−4.60 (10.95)*	−0.90 (10.95)
Total cholesterol (mg/dL)	−6.84 (32.90)*	+0.54 (32.90)
HDL cholesterol (mg/dL)	−0.19 (7.18)*	+1.53 (7.18)
LDL cholesterol (mg/dL)	−1.17 (28.29)	+2.36 (28.29)
Triglycerides (mg/dL)	−32.29 (63.82)	−24.09 (63.82)
Body mass index (kg/m^2)	−0.35 (1.27)*	+0.96 (1.27)
Severe hypoglycemia event rate (events per 100 patient years)	0.03	0.11
Non-severe hypoglycemia event rate (events per 100 patient years)	228.34*	1,091.44

Abbreviations. HbA1c, glycated hemoglobin; HDL, high density lipoprotein; LDL, low density lipoprotein.

*Statistically significant difference.

Non-severe hypoglycemia was defined as an episode that is blood-glucose confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with or without symptoms consistent with hypoglycemia, but does not meet the ADA classification of a severe event. Parameters listed above were derived from the DUAL VII trial¹². It should be noted that the changes presented by Billings et al. are not adjusted for differences between the IDegLira and insulin glargine U100 plus insulin aspart arms at baseline, but the estimated treatment difference presented is adjusted for these differences. The present analysis used the adjusted values for each treatment arm, reflecting the estimated treatment difference between the arms presented by Billings et al.¹². Change in HbA1c (the primary endpoint of the trial) was analyzed using a liner mixed model, with secondary continuous endpoints analyzed using a mixed model for repeated measurements (MMRM), and hypoglycemic events analyzed using a negative binomial regression model.

Table 3. Long-term cost-effectiveness outcomes.

	IDegLira, Mean (SD)	Insulin glargine U100 plusinsulin aspart, Mean (SD)	Difference
Discounted life expectancy (years)	14.33 (0.20)	14.31 (0.18)	+0.02
Discounted quality-adjusted life expectancy (QALYs)	9.55 (0.14)	9.33 (0.13)	+0.22
Discounted direct costs ($)	174,471 (2,362)	178,042 (2,174)	−3,571
ICER based on life expectancy and direct costs	IDegLira dominant
ICER based on quality-adjusted life expectancy and direct costs	IDegLira dominant

Abbreviations and symbols. $, United States dollars; ICER, incremental cost-effectiveness ratio; QALYs, quality-adjusted life years; SD, standard deviation.An intervention which is more effective than an alternative, while reducing costs is considered to be dominant over the comparator⁴².

Table 4. Sensitivity analysis results.

Analysis	Discounted quality-adjusted life expectancy (QALYs)			Discounted direct costs ($)			ICER ($ per QALY gained)
	IDegLira	Insulin glargine U100 plus insulin aspart	Difference	IDegLira	Insulin glargine U100 plus insulin aspart	Difference
Base case	9.55	9.33	+0.22	174,471	178,042	−3,571	IDegLira dominant
20 year time horizon	8.28	8.06	+0.22	144,726	148,177	−3,451	IDegLira dominant
10 year time horizon	5.48	5.28	+0.20	89,446	93,041	−3,595	IDegLira dominant
0% discount rates	13.49	13.23	+0.26	256,548	260,288	−3,740	IDegLira dominant
6% discount rates	7.20	7.01	+0.19	127,387	130,716	−3,329	IDegLira dominant
HbA1c difference abolished	9.55	9.33	+0.23	174,592	178,042	−3,450	IDegLira dominant
Systolic blood pressure difference abolished	9.54	9.33	+0.21	174,611	178,042	−3,431	IDegLira dominant
Lipid difference abolished (total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides)	9.55	9.33	+0.22	174,575	178,042	−3,467	IDegLira dominant
Body mass index difference abolished	9.50	9.33	+0.17	174,448	178,042	−3,594	IDegLira dominant
Hypoglycemia difference abolished	9.39	9.33	+0.06	174,799	178,042	−3,242	IDegLira dominant
Statistically significant differences only	9.55	9.33	+0.22	174,497	178,042	−3,545	IDegLira dominant
Observed treatment effects	9.57	9.33	+0.23	174,606	177,677	−3,071	IDegLira dominant
HbA1c benefit maintained	9.56	9.33	+0.23	174,647	178,042	−3,394	IDegLira dominant
UKPDS HbA1c creep	8.90	8.67	+0.23	175,390	178,732	−3,342	IDegLira dominant
Upper 95% CI of HbA1c change in IDegLira arm	9.56	9.33	+0.23	174,462	178,042	−3,579	IDegLira dominant
Lower 95% CI of HbA1c change in IDegLira arm	9.54	9.33	+0.21	174,631	178,042	−3,410	IDegLira dominant
Body mass index benefit maintained after treatment switch	9.57	9.33	+0.24	174,439	178,042	−3,603	IDegLira dominant
Treatment switching at 3 years in IDegLira arm	9.48	9.33	+0.15	175,874	178,042	−2,168	IDegLira dominant
Treatment switching at 7 years in IDegLira arm	9.62	9.33	+0.29	173,359	178,042	−4,682	IDegLira dominant
No treatment switching	10.00	9.33	+0.67	166,496	178,042	−11,546	IDegLira dominant
Costs of complications +10%	9.55	9.33	+0.22	175,978	179,631	−3,654	IDegLira dominant
Costs of complications −10%	9.55	9.33	+0.22	173,019	176,525	−3,506	IDegLira dominant
Alternative hypoglycemia disutilities	9.62	9.43	+0.20	174,471	178,042	−3,571	IDegLira dominant
28% of patients in insulin glargine U100 plus insulin aspart arm receiving twice daily insulin glargine U100 (IDegLira matched after intensification)	9.55	9.33	+0.22	174,918	178,679	−3,761	IDegLira dominant
Two injection per day in insulin glargine U100 plus insulin aspart arm (IDegLira matched after intensification)	9.55	9.33	+0.22	170,870	172,914	−2,045	IDegLira dominant
Needle and SMBG costs not included	9.55	9.33	+0.22	152,465	151,580	+886	4,050
Cost of NPH insulin applied in insulin glargine U100 plus insulin aspart arm (IDegLira matched after intensification)	9.55	9.33	+0.22	152,271	146,432	+5,839	26,699
Cost of biosimilar insulin glargine U100 applied in insulin glargine U100 plus insulin aspart arm (IDegLira matched after intensification)	9.55	9.33	+0.22	166,989	167,390	−400	IDegLira dominant
UKPDS 82 equations used	9.89	9.67	+0.22	182,525	185,820	−3,295	IDegLira dominant
PSA	9.25	9.02	+0.23	171,487	174,897	−3,411	IDegLira dominant

Abbreviations. $, United States dollars; CI, confidence interval; HbA1c, glycated hemoglobin; HDL, high-density lipoprotein; ICER, incremental cost-effectiveness ratio; LDL, low-density lipoprotein; NPH, neutral protamine Hagedorn; PSA, probabilistic sensitivity analysis; SMBG, self-monitoring of blood glucose; UKPDS, United Kingdom Prospective Diabetes Study.

An intervention which is more effective than an alternative, while reducing costs, is considered to be dominant over the comparator⁴².

Billings LK, Doshi A, Gouet D, et al. Efficacy and safety of IDegLira versus basal-bolus insulin therapy in patients with type 2 diabetes uncontrolled on metformin and basal insulin: the DUAL VII randomized clinical trial. Diabetes Care 2018;41:1009-16

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