Evaluation of the long-term cost-effectiveness of liraglutide therapy for patients with type 2 diabetes in France

Figures & data

Table 1. Baseline characteristics of the simulated cohorts.

Characteristic	LIRA-DPP416 (mean (SD))	LEAD-218 (mean (SD))
Age (years)	55.3 (9.2)	55.8 (9.0)
Duration of diabetes (years)	6.0 (4.5)	6.0 (4.7)
Males (%)	52.9	54.2
HbA1c (%)	8.4 (0.8)	8.3 (1.1)
SBP (mmHg)	132.2 (14.6)	130.6 (14.0)
Total cholesterol (mg/dL)	185.1 (44.1)	188.6 (43.3)
HDL cholesterol (mg/dL)	44.6 (12.1)	49.7 (12.6)
LDL cholesterol (mg/dL)	102.3 (31.6)	119.9 (34.4)
Triglycerides (mg/dL)	210.5 (196.3)	194.1 (146–9)
Body mass index (kg/m^2)	32.8 (5.2)	31.0 (4.7)

HbA1c, glycated hemoglobin; HDL, high density lipoprotein; LDL, low density lipoprotein SBP, systolic blood pressure; SD, standard deviation. In the LEAD-2 analysis only patients in which liraglutide or glimepiride was added to ongoing metformin monotherapy (∼30% of the total trial population) were included, as this was considered to be more reflective of clinical practice and brings the analysis into line with the LIRA-DPP4 comparison.

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

Physiological parameter	Liraglutide vs sitagliptin17			Liraglutide vs glimepiride18
	Liraglutide 1.2 mg (mean (SD))	Sitagliptin 100 mg (mean (SD))	Difference	Liraglutide 1.2 mg (mean (SD))	Glimepiride 4 mg (mean (SD))	Difference
Change in HbA1c (%)	−1.29 (1.05)	−0.88 (1.04)	−0.41	−1.25 (1.02)	−1.16 (0.97)	−0.10
Change in SBP (mmHg)	−0.37 (13.95)	−1.03 (13.76)	+0.66	−3.33 (12.90)	+2.26 (12.65)	−5.59
Change in total cholesterol (mg/dL)	−0.39 (34.80)	1.16 (34.34)	−1.55	−0.77 (21.72)	+3.31 (30.88)	−4.07
Change in HDL cholesterol (mg/dL)	0.39 (5.80)	0.39 (5.72)	0.00	+0.79 (8.02)	−0.82 (7.84)	+1.62
Change in LDL cholesterol (mg/dL)	3.48 (29.00)	6.57 (28.61)	−3.09	+5.73 (26.42)	+8.49 (25.71)	−2.76
Change in triglycerides (mg/dL)	−8.86 (132.86)	−20.37 (131.07)	+11.51	−39.27 (114.28)	−0.82 (7.84)	−17.43
Change in body mass index (kg/m^2)	−0.93 (—)	−0.33 (—)	−0.57	−0.64 (0.95)	+0.48 (3.69)	−1.12
Major hypoglycemic events (per 100 patient years)	0.60	0.00	+0.60	0.00	0.00	0.00
Minor hypoglycemic events (per 100 patient years)	14.30	13.70	+0.60	4.90	217.20	−212.30

HbA1c, glycated hemoglobin; HDL, high density lipoprotein; LDL, low density lipoprotein SBP, systolic blood pressure; SD, standard deviation. In the LEAD-2 analysis only patients in which liraglutide or glimepiride was added to ongoing metformin monotherapy (∼30% of the total trial population) were included, as this was considered to be more reflective of clinical practice and brings the analysis into line with the LIRA-DPP4 comparison.

Table 3. Cost-effectiveness outcomes of the base case analyses.

Liraglutide vs sitagliptin	Liraglutide 1.2 mg (mean (SD))	Sitagliptin 100 mg (mean (SD))	Difference
Undiscounted life expectancy (years)	23.46 (0.37)	23.05 (0.37)	+0.41
Discounted life expectancy (years)	15.62 (0.20)	15.43 (0.20)	+0.19
Discounted quality-adjusted life expectancy (QALYs)	10.09 (0.13)	9.84 (0.13)	+0.25
Discounted direct costs (EUR)	43,031 (1532)	40,472 (1513)	+2558
ICER (EUR per QALY gained)			10,275
Liraglutide vs glimepiride	Liraglutide 1.2 mg (mean (SD))	Glimepiride (mean (SD))	Difference
Undiscounted life expectancy (years)	23.48 (0.39)	23.16 (0.36)	+0.32
Discounted life expectancy (years)	15.63 (0.21)	15.47 (0.19)	+0.16
Discounted quality-adjusted life expectancy (QALYs)	10.25 (0.14)	10.02 (0.13)	+0.23
Discounted direct costs (EUR)	41,481 (1339)	36,786 (1229)	+4695
ICER (EUR per QALY gained)			20,709

EUR, 2013 Euros; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life year.

Figure 1. Mean direct costs associated with liraglutide 1.2 mg and sitagliptin over patient lifetimes. EUR, 2013 Euros.

Table 4. Liraglutide vs sitagliptin: Results of the sensitivity analyses.

Analysis	Quality-adjusted life expectancy (QALYs)			Costs (EUR)			ICER (EUR per QALY gained)
	Liraglutide	Sitagliptin	Difference (95% CI)	Liraglutide	Sitagliptin	Difference (95% CI)
Base case	10.09	9.84	0.25 (0.24–0.26)	43,031	40,473	2558 (2427–2689)	10,275
Indirect costs included	10.09	9.84	0.25 (0.24–0.26)	50,747	48,458	2289 (2156–2423)	9197
20-year time horizon	8.33	8.17	0.15 (0.15–0.16)	32,005	28,636	3369 (3253–3486)	22,028
10-year time horizon	5.39	5.33	0.06 (0.06–0.06)	19,258	15,598	3660 (3573–3747)	61,634
5-year time horizon	3.09	3.05	0.03 (0.03–0.04)	11,626	7776	3850 (3794–3906)	114,401
0% discount rate	14.86	14.40	0.46 (0.44–0.48)	68,274	66,268	2007 (1792–2221)	4372
5% discount rate	8.15	7.98	0.17 (0.17–0.18)	33,538	30,829	2708 (2604–2812)	15,606
Alternative costs of complications	10.09	9.85	0.25 (0.24–0.26)	40,156	37,825	2331 (2200–2461)	9457
No HbA1c difference	9.89	9.84	0.05 (0.03–0.05)	44,304	40,473	3831 (3608–3867)	81,511
No SBP difference	10.10	9.84	0.26 (0.25–0.27)	43,062	40,473	2589 (2460–2717)	10,113
No lipid difference	10.10	9.84	0.26 (0.24–0.27)	43,227	40,473	2754 (2529–2790)	10,511
No BMI difference	10.05	9.84	0.21 (0.19–0.21)	43,189	40,473	2716 (2488–2755)	12,933
No hypoglycemia difference	10.10	9.84	0.26 (0.24–0.26)	42,932	40,473	2459 (2247–2483)	9643
Statistically significant differences only	10.10	9.84	0.26 (0.24–0.26)	43,132	40,473	2659 (2436–2693)	10,387
HbA1c difference abolished on treatment switching	9.98	9.84	0.14 (0.12–0.14)	44,067	40,473	3594 (3370–3629)	25,856
UKPDS creep	9.38	9.28	0.10 (0.09–0.11)	49,350	45,541	3809 (3654–3964)	38,090
Treatment switch after 7 years	10.13	9.87	0.26 (0.25–0.27)	44,327	40,239	4089 (3958–4220)	15,641
Treatment switch after 3 years	10.07	9.84	0.23 (0.22–0.24)	42,189	40,825	1364 (1225–1503)	5951
Switch to liraglutide 1.8 mg after 2 years	10.07	9.84	0.25 (0.24–0.26)	44,723	40,473	4250 (4119–4381)	17,071
France-specific cohort	9.05	8.81	0.24 (0.23–0.26)	47,065	44,377	2688 (2527–2848)	10,994
Probabilistic sensitivity analysis	9.80	9.56	0.24 (0.23–0.25)	44,837	42,038	2799 (2647–2951)	11,777

BMI, body mass index; CI, confidence interval; EUR, 2013 Euros; HbA1c; glycated hemoglobin; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life year; SBP, systolic blood pressure; UKPDS, United Kingdom Prospective Diabetes Study.

Figure 2. Liraglutide vs sitagliptin: Cost-effectiveness scatterplot for the probabilistic sensitivity analyses. EUR, 2013 Euros, QALY, quality-adjusted life year.

Figure 3. Liraglutide vs sitagliptin: Cost-effectiveness acceptability curve for the probabilistic sensitivity analysis. EUR, 2013 Euros; QALY, quality-adjusted life year.

Figure 4. Mean direct costs associated with liraglutide 1.2 mg and glimepiride over patient lifetimes EUR, 2013 Euros; QALYs, quality-adjusted life years.

Table 5. Liraglutide vs glimepiride: Results of the sensitivity analyses.

Analysis	Quality-adjusted life expectancy (QALYs)			Costs (EUR)			ICER (EUR per QALY gained)
	Liraglutide	Glimepiride	Difference (95% CI)	Liraglutide	Glimepiride	Difference (95% CI)
Base case	10.25	10.02	+0.23 (0.22–0.24)	41,481	36 786	[phone])	20 709
Indirect costs included	10.25	10.02	+0.23 (0.22–0.24)	49,466	45 050	[phone])	19 482
20-year time horizon	8.42	8.27	+0.16 (0.15–0.17)	30,586	25,764	[phone])	30,598
10-year time horizon	5.44	5.33	+0.11 (0.11–0.11)	18,095	13,038	[phone])	46,055
5-year time horizon	3.12	3.03	+0.09 (0.09–0.09)	10,665	5401	[phone])	57,285
0% discount rate	15.14	14.77	+0.37 (0.34–0.39)	66,167	61,470	[phone])	14,431
5% discount rate	8.27	8.09	+0.18 (0.17–0.19)	32,149	27,641	[phone])	25,195
Alternative costs of complications	10.25	10.02	+0.23 (0.22–0.24)	39,565	34,703	[phone])	21,846
No HbA1c difference	10.21	10.02	+0.19 (0.18–0.20)	41,783	36,786	[phone])	26,580
No SBP difference	10.21	10.02	+0.19 (0.18–0.20)	41,772	36,786	[phone])	25,834
No lipid difference	10.21	10.02	+0.19 (0.17–0.20)	41,740	36,786	[phone])	26,634
No BMI difference	10.19	10.02	+0.17 (0.16–0.18)	41,463	36,786	[phone])	27,675
No hypoglycemia difference	10.22	10.02	+0.20 (0.18–0.21)	41,501	36,786	[phone])	23,813
Statistically significant differences only	10.17	10.02	+0.15 (0.13–0.16)	42,061	36,786	[phone])	35,884
HbA1c difference abolished on treatment switching	10.24	10.02	+0.22 (0.20–0.23)	41,693	36,786	[phone])	22,613
UKPDS creep	9.55	9.36	+0.19 (0.18–0.20)	47,068	42,338	[phone])	24,740
Treatment switch after 7 years	10.29	10.02	+0.26 (0.25–0.27)	42,529	35,941	[phone])	25,059
Treatment switch after 3 years	10.23	10.03	+0.20 (0.19–0.21)	40,463	37,868	[phone])	12,809
Switch to liraglutide 1.8 mg after 2 years	10.25	10.02	+0.23 (0.22–0.24)	43,263	36,786	[phone])	28,533
France-specific cohort	9.25	9.01	+0.24 (0.23–0.25)	46,590	42,119	[phone])	25,114
Probabilistic sensitivity analysis	9.90	9.68	+0.23 (0.22–0.24)	42,697	38,201	[phone])	19,803

BMI, body mass index; CI, confidence interval; EUR, 2013 Euros; HbA1c; glycated hemoglobin; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life year; SBP, systolic blood pressure; UKPDS, United Kingdom Prospective Diabetes Study.

Figure 5. Liraglutide vs glimepiride: Cost-effectiveness scatterplot for the probabilistic sensitivity analyses. EUR, 2013 Euros, QALY, quality-adjusted life year.

Figure 6. Liraglutide vs glimepiride: Cost-effectiveness acceptability curve for the probabilistic sensitivity analysis. EUR, 2013 Euros; QALY, quality-adjusted life year.

Pratley RE, Nauck M, Bailey T, et al; 1860-LIRA-DPP-4 Study Group. Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet 2010;375:1447-56

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