Cost-effectiveness of once daily GLP-1 receptor agonist lixisenatide compared to bolus insulin both in combination with basal insulin for the treatment of patients with type 2 diabetes in Norway

Figures & data

Table 1. Cohort characteristics and patient management practices.

	Mean (SD)	Reference
Patient demographics
Baseline age (years)	57.2 (9.6)	GetGoal-L
Duration of diabetes (years)	12.5 (6.8)	GetGoal-L
Proportion male	46.0%	GetGoal-L
Baseline risk factors
HbA1c (% points)	8.4 (0.9)	GetGoal-L
Systolic blood pressure (mmHg)	130.4 (14.4)	GetGoal-L
Total cholesterol (mg/dL)	182.2 (41.7)	GetGoal-L
High-density lipoprotein cholesterol (mg/dL)	44.9 (12.3)	GetGoal-L
Low-density lipoprotein cholesterol (mg/dL)	104.9 (37.6)	GetGoal-L
Triglycerides (mg/dL)	176.0 (111.9)	GetGoal-L
BMI (kg/m^2)	32.1 (6.2)	GetGoal-L
Proportion smokers	10.0%	GetGoal-L
Cigarettes per day	1.0	GetGoal-L
Alcohol consumption (Oz/week)	5.0	GetGoal-L
Racial characteristics
Proportion White	52.3%	GetGoal-L
Proportion Black	3.9%	GetGoal-L
Proportion Hispanic	27.0%	GetGoal-L
Proportion Native American	0.2%	GetGoal-L
Proportion Asian/Pacific Islander	16.6%	GetGoal-L
Cardiovascular medication
Aspirin use for primary prevention	31.4%	Expert Opinion
Aspirin use for secondary prevention	86.0%	25
ACE inhibitor use for primary prevention	64.4%	26
ACE inhibitor for secondary prevention	94.0%	25
Statins use for primary prevention	45.9%	Expert Opinion
Statins use for secondary prevention	73.0%	25
Complications management
Proportion on foot ulcer prevention program	10.9%	27
Proportion screened for retinopathy	85.0%	28
Proportion screened for renal disease	59.7%	27
Proportion receiving intensive insulin after MI	87.7%	29
Proportion treated with extra ulcer treatment (Regranex)	57.0%	30
Proportion screened for depression – no complications	83.0%	31
Proportion screened for depression – complications	83.0%	31

ACE = angiotensin-converting enzyme; BMI = body mass index; HbA1c = glycohemoglobin; MI = myocardial infarction; Oz = fluid ounces.

Table 2. Simulated diabetes complication and intervention costs.

Diabetes Complication	Costs (NOK)	DoW
Myocardial infarction, year of event	161,898	44
Myocardial infarction, subsequent years	3907	0
Angina, year of onset	36,299	31
Angina, subsequent years	6653	0
Heart failure, year of onset	59,000	49
Heart failure, subsequent years	8840	0
Stroke, year of event	208,634	59
Stroke, subsequent years	93,394	0
Stroke, death within 30 days	41,814	0
PVD, year of onset	37,646	37
PVD, subsequent years	2917	0
Hemodialysis, year of onset	560,323	18
Hemodialysis, subsequent years	560,323	18
Peritoneal dialysis, year of onset	553,951	18
Peritoneal dialysis, subsequent years	553,951	18
Kidney transplant, year of procedure	423,897	18
Kidney transplant, subsequent years	41,612	18
Major hypoglycemic event	5042	14
Minor hypoglycemic event	134	0
Laser treatment	22,445	0
Cataract operation	15,739	10
Annual cost following cataract operation	775	0
Blindness, first year	5588	38
Blindness, subsequent years	5588	0
Neuropathy, year of onset	4958	24
Neuropathy, subsequent years	0	0
Uninfected foot ulcer, year of onset	14,433	19
Uninfected foot ulcer, subsequent years	14,433	0
Infected foot ulcer, year of onset	52,053	19
Infected foot ulcer, subsequent years	52,053	0
Amputation, procedure	129,426	27
Amputation, prosthesis	16,730	0
Annual cost following amputation	0	0
Gangrene treatment, year of onset	21,580	37
Annual cost following gangrene treatment	0	0
Cost after healed ulcer	12,559	19
Cost after healed ulcer (post-amputation)	221,827	0
Diabetes intervention	Lixisenatide plus insulin	Basal–bolus insulin
Cost per needle	1.28	1.28
Number of needles per day	2.00	4.00
Cost per lancet and test strip	6.69	6.69
Number of lancets and test strips per day	1.00	4.00
Basal insulin dose per day (IU)	51.73	62.60
Basal insulin cost per IU	0.21	0.21
Bolus insulin dose per day (IU)	0.00	62.60
Bolus insulin cost per IU	0.20	0.20
Lixisenatide cost per day	21.84	0.00
Annual cost (NOK)	15,307	21,103

DoW = days off work; IU = international units; NOK = Norwegian krone; PVD = peripheral vascular disease.

Table 3. Summary cost, clinical and cost-effectiveness results for lixisenatide plus insulin versus basal–bolus insulin.

Summary cost outcomes	Lixisenatide plus insulin	Basal–bolus insulin
Direct costs from payer perspective (NOK)	742,563	750,032
Treatment	226,553	242,034
Patient management	15,143	15,113
Cardiovascular disease	138,693	139,846
Renal disease	25,707	23,132
Diabetic foot and neuropathy	297,674	291,327
Eye disease	12,425	12,030
Hypoglycemia	24,682	24,874
Depression	1685	1675
Indirect costs	508,827	508,227
Combined costs from societal perspective (NOK)	1,251,390	1,258,259
Summary clinical outcomes
Quality-adjusted life expectancy (QALYs)	6.908	6.842
Cumulative incidence of complications
Background retinopathy (%)	22.228	21.405
Proliferative retinopathy (%)	2.146	1.983
Macular edema (%)	18.279	17.517
Severe vision loss (%)	16.125	15.478
Cataract (%)	9.211	9.059
Microalbuminuria (%)	35.179	34.015
Gross proteinuria (%)	12.666	11.875
End-stage renal disease (%)	3.963	3.546
Nephropathy-related death (%)	2.240	2.025
Foot ulcer, first (%)	41.032	40.070
Foot ulcer, recurrence (%)	98.821	97.274
Amputation (%)	18.832	18.476
Neuropathy (%)	62.907	61.660
Peripheral vascular disease (%)	11.856	11.617
Congestive heart failure, onset (%)	36.556	38.232
Congestive heart failure, death (%)	26.097	27.289
Angina (%)	13.727	13.464
Myocardial infarction, event (%)	31.258	31.085
Myocardial infarction, death (%)	16.864	16.720
Stroke, event (%)	19.686	19.729
Stroke, death (%)	6.524	6.477
Summary cost-effectiveness outcomes
ICER based on quality-adjusted life expectancy, payer perspective	Dominant*
ICER based on quality-adjusted life expectancy, societal perspective	Dominant*

ICER = incremental cost-effectiveness ratio; NOK = Norwegian krone; QALY = quality-adjusted life year. Values shown are means.

*More effective and less costly.

Figure 1. Scatterplot of change in costs and change in quality-adjusted life expectancy for lixisenatide plus insulin versus basal–bolus insulin. NOK = Norwegian krone; QALY = quality-adjusted life year.

Table 4. Sensitivity analysis results for lixisenatide plus insulin versus basal–bolus insulin.

	Quality-adjusted life expectancy (QALYs)			Lifetime societal costs (NOK)
Sensitivity analysis	Lixisenatide plus insulin	Basal–bolus insulin	Difference	Lixisenatide plus insulin	Basal–bolus insulin	Difference	ICER (NOK per QALY gained)	NMB (NOK)
Base case	6.908 (0.097)	6.842 (0.093)	0.066	1,251,390 (50,965)	1,258,259 (48,538)	−6869	Dominant	39,369
5 year initial treatment duration	6.996 (0.097)	6.927 (0.097)	0.069	1,235,250 (51,104)	1,247,583 (51,936)	−12,333	Dominant	46,833
HbA1c dependent treatment switch	7.101 (0.099)	7.055 (0.100)	0.046	1,208,474 (49,784)	1,230,477 (52,035)	−22,003	Dominant	45,003
20 year time horizon	6.580 (0.087)	6.514 (0.092)	0.066	1,145,715 (48,422)	1,156,894 (50,129)	−11,179	Dominant	44,179
0% discount rates for costs and clinical outcomes	9.808 (0.167)	9.708 (0.162)	0.100	1,868,009 (77,757)	1,867,866 (73,710)	143	1422	49,857
6% discount rates for costs and clinical outcomes	5.953 (0.077)	5.899 (0.073)	0.054	1,055,187 (43,076)	1,063,694 (41,124)	−8507	Dominant	35,507
4% discount rate for costs and 0% for clinical outcomes	9.808 (0.167)	9.708 (0.162)	0.100	1,251,390 (50,965)	1,258,259 (48,538)	−6869	Dominant	56,869
Upper limit of 95% CI for change in HbA1c from baseline	6.935 (0.106)	6.907 (0.104)	0.028	1,244,979 (52,304)	1,242,843 (50,757)	2136	76,066	11,864
Lower limit of 95% CI for change in HbA1c from baseline	6.873 (0.102)	6.770 (0.096)	0.103	1,257,587 (51,083)	1,269,347 (50,551)	−11,760	Dominant	63,260
Upper limit of 95% CI for change in BMI from baseline	6.907 (0.093)	6.767 (0.268)	0.140	1,250,354 (52,981)	1,257,466 (50,780)	−7112	Dominant	39,231
Lower limit of 95% CI for change in BMI from baseline	6.905 (0.096)	6.859 (0.093)	0.046	1,248,525 (51,645)	1,258,256 (50,684)	−9731	Dominant	32,731
Complication costs increased by 25%	6.908 (0.097)	6.842 (0.093)	0.066	1,360,360 (57,233)	1,365,600 (54,813)	−5240	Dominant	38,240
Complication costs decreased by 25%	6.908 (0.097)	6.842 (0.093)	0.066	1,142,420 (44,894)	1,150,919 (42,482)	−8499	Dominant	41,499
Health state utility and disutility values increased by 25%	8.907 (0.124)	8.839 (0.119)	0.068	1,251,390 (50,965)	1,258,259 (48,538)	−6869	Dominant	40,869
Health state utility and disutility values decreased by 25%	4.763 (0.067)	4.697 (0.064)	0.066	1,251,390 (50,965)	1,258,259 (48,538)	−6869	Dominant	39,869
No CODE-2 disutility for BMI >25 kg/m^2	7.292 (0.102)	7.290 (0.098)	0.002	1,251,390 (50,965)	1,258,259 (48,538)	−6869	Dominant	7869
Norwegian cohort analysis	7.244 (0.097)	7.196 (0.094)	0.048	934,391 (40,655)	940,415 (37,908)	−6024	Dominant	30,024
Cost of basal insulin as NPH	6.908 (0.097)	6.842 (0.093)	0.066	1,242,084 (50,907)	1,248,580 (48,487)	−6496	Dominant	39,469

BMI = body mass index; HbA1c = glycohemoglobin; ICER = incremental cost-effectiveness ratio; NOK = Norwegian krone; QALY = quality-adjusted life year; SBP = systolic blood pressure.

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