Cost-effectiveness analysis of exenatide once-weekly versus dulaglutide, liraglutide, and lixisenatide for the treatment of type 2 diabetes mellitus: an analysis from the UK NHS perspective

Figures & data

Table 1. Baseline patient characteristics applied in the model.

Characteristic	Value
Current age (years)	54.90*
Proportion female	0.39
Duration of type 2 diabetes mellitus (years)	6.20*
Height (meters)	1.68
Proportion Afro-Caribbean	0.08
Proportion smokers	0.31
HbA1c (glycosylated hemoglobin, %)	7.50**
Total cholesterol (mg/dL)	207.69
High-density lipoprotein cholesterol (mg/dL)	41.15
Systolic blood pressure (mmHg)	129.70*
Weight (kg)	92.10*

Source: UKPDS^33,20, except *Kayaniyil et al.⁸, and **NICE¹⁹.

Table 2. Treatment efficacy and tolerability applied in the model.

	EQW	DULA	LIRA 1.2	LIRA 1.8	LIXI	NPH
ΔHbA1c (glycosylated hemoglobin, %)	−1.34	−1.34	−0.96	−1.28	−0.75	−0.54
ΔWeight (kg)	−2.04	−2.38	−2.72	−3.09	−1.84	1.703
Discontinuation due to adverse event*	0.063	0.140	0.120	0.130	0.030	NA
Nausea as adverse event*	0.240	0.520	0.440	0.490	0.310	NA
Symptomatic hypoglycemia#	NA	NA	NA	NA	NA	10.922
Severe hypoglycemia∼	NA	NA	NA	NA	NA	0.02

Source: Kayaniyil et al.⁸, except NPH¹⁹.

EQW, exenatide 2 mg QW; DULA, dulaglutide 1.5 mg QW; LIRA 1.2, liraglutide 1.2 mg QD; LIRA 1.8, liraglutide 1.8 mg QD; LIXI, lixisenatide 20 μg QD; NPH, Neutral Protamine Hagedorn insulin; NA, Not available; Δ, change from baseline.

* proportion applied in the first 6-month cycle; #number of episodes per year; ∼probability per 6 months.

Table 3. Cost inputs applied in the model.

Drug	Price per pack or unit	Doses per pack	Doses per week	Annual cost
Exenatide QW	£73.36^a	4	1	£986.18^b
Dulaglutide 1.5 mg QW	£73.25^a	4	1	£984.74^b
Liraglutide 1.2 mg QD	£117.72^a	45	7	£1,032.27^b^,^c
Liraglutide 1.8 mg QD	£117.72^a	30	7	£1,510.02^b^,^c
Lixisenatide 20 μg QD	£57.93^a	28	7	£820.29^b^,^c
NPH insulin	—	—	—	£606.27^d
Diabetes related complication‡	Fatal	Non-fatal	Maintenance	Reference
Ischemic heart disease	—	£12,762	£1,395	Alva et al.^24
Myocardial infarction	£2,605	£7,938	£2,177
Congestive heart failure	—	£5,180	£1,656
Stroke	£5,188	£11,450	£1,378
Blindness	—	£6,502	£2,307
End stage renal disease	—	£18,776	£18,776
Amputation	—	£13,499	£4,618	Baboolal et al.^46
Adverse event and discontinuation	Cost	Reference
Severe hypoglycemic event^	£424	Hammer et al.^47
Nausea	£46	Assumed to incur one GP visit^25
Discontinuation due to AE	£46	Assumed to incur one GP visit^25

^a Sourced from www.mims.co.uk. Accessed January 2016.

^b Cost includes metformin 2000 mg per day¹⁹.

^c Includes cost of needles, sourced from www.mims.co.uk, accessed January 2016.

^d Cost assumes 57.2 units per day¹⁹. Cost includes metformin 2252 mg per day, consumables (test strips, needles, sharps bin), and insulin initiation in the first year of treatment¹⁹.

‡ Costs were inflated into 2014 values, using the Hospital and Community Health Services Pay and Price index²⁵.

^ Cost input was based on an assumed distribution of 65% hospital treatment and 35% non-hospital treatment.

Table 4. Utility decrements applied in the model.

Event	Utility decrement	Reference
Diabetes-related complications
Ischemic heart disease	0.090	Clarke et al.^26
Myocardial infarction	0.055	Clarke et al.^26
Congestive heart failure	0.108	Clarke et al.^26
Stroke	0.164	Clarke et al.^26
Amputation	0.280	Clarke et al.^26
Blindness	0.074	Clarke et al.^26
End stage renal disease	0.263	Currie et al.^27
Hypoglycemia
Symptomatic	0.0142	Currie et al.^28
Severe	0.047	Currie et al.^28
BMI change	Utility change
Per unit increase	−0.0061	Bagust and Beale^21
Per unit decrease	+0.0061	Bagust and Beale^21

Table 5. Results (discounted) of exenatide QW and comparators: Base case and probabilistic sensitivity analysis.

	Total lifetime cost (per patient)	QALYs (per patient)	Incremental* costs	Incremental* QALYs	ICER
Base case analysis
Exenatide QW	£19,930	11.279
Dulaglutide 1.5 mg QW	£19,903	11.233	£27 (−£30; £85)	0.046 (0.036; 0.056)	£596
Liraglutide 1.2 mg QD	£19,827	11.177	£103 (£46; £160)	0.102 (0.093; 0.112)	£1,004
Liraglutide 1.8 mg QD	£22,016	11.236	−£2,085 (−£2,143; −£2,028)	0.043 (0.034; 0.053)	EQW dominant
Lixisenatide 20 μg QD	£19,192	11.206	£738 (£681; £795)	0.074 (0.064; 0.083)	£10,002
PSA
Exenatide QW	£20,023	11.500
Dulaglutide 1.5 mg QW	£19,957	11.463	£67 (−£345; £482)	0.036 (−0.072; 0.143)	£1,846
Liraglutide 1.2 mg QD	£20,026	11.409	−£3 (−£464, £467)	0.090 (−0.022; 0.177)	EQW dominant
Liraglutide 1.8 mg QD	£21,886	11.479	−£1,863 (−£2,494; −£1,136))	0.021 (−0.080; 0.117))	EQW dominant
Lixisenatide 20 μg QD	£19,322	11.418	£701 (£286; £1,094)	0.082 (−0.009; 0.169)	£8,599

* exenatide QW vs comparator.

QALYs, quality-adjusted life years; ICER, incremental cost-effectiveness ratio; EQW, exenatide QW; PSA, probabilistic sensitivity analysis. CIs are based on the mean values analysis.

Table 6. Disaggregated base case incremental cost (£) calculated for exenatide QW vs comparators.

Parameters	Incremental cost of exenatide QW vs
	Dulaglutide 1.5 mg QW	Liraglutide 1.2 mg QD	Liraglutide 1.8 mg QD	Lixisenatide 20 μg QD
Treatment related
Drug treatment (total)	£146	£239	−£1965	£865
Hypoglycemia	−£2	−£8	−£2	−£5
Nausea	−£16	−£17	−£14	−£7
Event-related
Ischemic heart disease	−£26	−£24	−£13	−£20
Myocardial infarction	−£11	−£15	−£5	−£1
Congestive heart failure	−£9	−£16	−£13	−£13
Stroke	−£6	−£4	−£9	−£12
Blindness	−£8	−£4	−£7	−£16
Nephropathy	−£21	−£6	−£41	−£20
Amputation	−£20	−£42	−£16	−£32
Total	£27	£103	−£2085	£738

Figure 1. Cost-effectiveness acceptability curves of individual comparisons; exenatide QW vs comparators.EQW, exenatide QW; DULA, dulaglutide 1.5 mg QW; LIRA 1.2, liraglutide 1.2 mg QD; LIRA 1.8, liraglutide 1.8 mg QD; LIXI, lixisenatide 20 μg QD.

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