The cost-effectiveness of exenatide twice daily (BID) vs insulin lispro three times daily (TID) as add-on therapy to titrated insulin glargine in patients with type 2 diabetes

Figures & data

Table 1. Data inputs: Baseline characteristics and treatment effects (mean, SE*).

Patient characteristic	Input
Current age (years)	59.80 (0.379)
Proportion female (%)	50
Duration diabetes (years)	12.80 (0.284)
Height (m)†	1.66 (0.17)
Proportion AC	0.01
Proportion current smokers	0.13
HbA1c (%)‡	8.20 (0.037)
Total cholesterol (mg/dl)§	177.56 (39.76)
HDL cholesterol (mg/dl)§	46.32 (12.55)
SBP (mmHg)	135.80 (0.623)
Weight (kg)	89.60 (0.678)
Treatment effects	Model arm		Rescue therapy
	Exenatide BID	Lispro TID	Exenatide BID	Lispro TID
HbA1c (%)†	−1.10 (0.051)	−1.10 (0.051)	−1.93 (0.19)	−1.93 (0.19)
HbA1c (mmol/mol)∥	−12 (0.5)	−12 (0.5)	−21.1 (2.1)	−21.1(2.1)
SBP (mmHg)	−3.77 (0.906)	0.17 (0.889)	n/a	n/a
Total cholesterol (mg/dl)§	−6.56 (1.814)	−1.54 (1.814)	n/a	n/a
HDL cholesterol (mg/dl)§	−1.16 (0.425)	1.16 (0.463)	n/a	n/a
Weight (kg)	−2.60 (0.250)	1.90 (0.240)	4.10 (0.307)	4.10 (0.307)

AC, Afro-Caribbean; BID, twice daily; HDL, high-density lipoprotein; SBP, systolic blood pressure; SD, standard deviation; SE, standard error; TID, three times daily.

Data sourced from intention-to-treat population from 4B Study at time of randomization and at end of study^2,33 and Rosenstock et al.¹² studies.

* Where SD reported, SE was calculated as SE = SD/SQRT (n).

† SE assumed 10% of mean value for height and HbA_1c rescue therapy (data not reported).

‡ Mean = 66 mmol/mol; SE = 0.4 mmol/mol (calculated based on HbA_1c %)

§ Conversion factor from mmol/l to mg/dl =38.6³⁴.

∥ Calculated based on HbA_1c %.

Table 2. Data inputs: Annual cost of medications and complications (€EUR) and health state utility changes.

Cost of medications	Model arm		Rescue therapy (cost/unit/kg/day)
	Exenatide BID	Lispro TID	Exenatide BID	Lispro TID
Exenatide BID	1,254	—	—	—
Glargine	808	732	0	0
Lispro TID	—	350	0	0
Metformin	47	47	47	47
Consumables (annual)	328	917	917	917
Total	2,437	2,046	—	—
Cost of complications	Fatal	Non-fatal		Maintenance
Ischemic heart disease		12,310		544
Myocardial infarction	5,478	10,380		244
Congestive heart failure	8,139	8,139		770
Stroke	9,078	9,331		394
Amputation	17,763	17,763		288
Blindness		2,338		753
ESRD		13,559		884
Moderate hypoglycemia		374
Discontinuations		142
Health state utility changes	Value		Source
Age dependent baseline	Time dependent		DoH^11
Ischemic heart disease	−0.09		Clarke et al.^35
Myocardial infarction	−0.055		Clarke et al.^35
Congestive heart failure	−0.108		Clarke et al.^35
Stroke	−0.164		Clarke et al.^35
Pre-blind	−0.029		Clarke et al.^35
Blind	−0.074		Currie et al.^20
ESRD	−0.263		Currie et al.^20
Transplant	−0.075		Clarke et al.^35
Amputation	−0.280		Clarke et al.^35
Nausea	−0.04		Matza et al.^36
BMI (utility per unit decrease)	+0.0171		Lane et al.^21
BMI (utility per unit increase)	−0.0472		Lane et al.^21
Discontinuation	0		Assumption

BID, twice daily; BMI, body mass index; ESRD, end-stage renal disease; TID,: three times daily.

Figure 1. Modeling weight progression.

Table 3. Expected costs, QALYs, and incremental cost-effectiveness (1000 people over 40 years): base case and deterministic sensitivity analysis (1000 people over 40 years).

Parameter	Costs (€EUR)		QALYs		Incremental		ICER
	Exen. BID	Lispro TID	Exen. BID	Lispro TID	Costs	QALYs	Cost/QALY
Base case	44,526	43,256	11.51	10.86	1,270	0.64	1,971
Discounting 0%	64,850	63,665	15.99	15.11	1,186	0.88	1,344
Discounting 6%	32,968	31,678	8.87	8.37	1,290	0.50	2,557
Time horizon 20 years	35,886	34,563	9.78	9.23	1,324	0.55	2,415
Complication utility (−)	44,526	43,256	11.79	11.25	1,270	0.53	2,394
Complication utility (+)	44,526	43,256	11.23	10.47	1,270	0.76	1,675
Complication costs (−)	43,359	42,091	11.51	10.86	1,268	0.64	1,968
Complication costs (+)	45,693	44,421	11.51	10.86	1,272	0.64	1,974
Cost of SHE^19	44,458	43,282	11.51	10.86	1,265	0.64	1,963
BMI-related utility^23	44,526	43,256	12.30	12.03	1,270	0.27	4,722
BMI-related utility^22	44,526	43,256	12.47	12.31	1,270	0.16	8,076
Weight convergence	44,620	43,256	11.40	10.86	1,365	0.53	2,568
Longer duration of treatment	44,993	43,326	12.04	11.24	2,667	0.80	3,343

Discounted costs, QALYs and cost per QALY per patient. Costs reported in EURO.

BID, twice daily; BMI, body mass index; Exen, exenatide; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-year; SHE, severe hypoglycemic event; TID, three times daily.

Diamant M, Nauck MA, Shaginian R, et al. Glucagon-like peptide-1 receptor agonist or bolus insulin with optimized basal insulin in diabetes. Diabetes Care 2014;37:2763-73

 PubMed Web of Science ®Google Scholar

Bristol-Myers Squibb Pharmaceuticals Ltd & Eli Lilly and Company. Final Clinical Study Report: H8O-EW-GWDM. A randomized trial comparing two therapies: Basal insulin glargine, exenatide and metformin therapy (BET) or basal insulin glargine, bolus insulin lispro and metformin therapy (BBT) in subjects with type 2 diabetes who were previously treated by basal insulin glargine with either metformin or metformin and sulfonylurea (4B: basal insulin glargine, exenatide BID, and metformin therapy or basal insulin glargine, bolus insulin lispro and metformin therapy). Indianapolis (Indiana, USA); 2013

 Google Scholar

Rosenstock J, Ahmann AJ, Colon G, et al. Advancing insulin therapy in type 2 diabetes previously treated with glargine plus oral agents prandial premixed (insulin lispro protamine suspension/lispro) versus basal/bolus (glargine/lispro) therapy. Diabetes Care 2008;31:20-5

 PubMed Web of Science ®Google Scholar

Reiner Z, Catapano AL, De Backer G, et al. ESC/EAS guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011;32:1769-818

 PubMed Web of Science ®Google Scholar

Department of Health. Health Survey for England; 2003. http://webarchive.nationalarchives.gov.uk/+/www.dh.gov.uk/en/publicationsandstatistics/publications/publicationsstatistics/dh_4098712. Accessed September 15, 2014

 Google Scholar

Clarke P, Gray A, Holman R. Estimating utility values for health states of type 2 diabetic patients using the EQ-5D (UKPDS 62). Med Decis Making 2002;22:340-9

 PubMed Web of Science ®Google Scholar

Currie CJ, Morgan CL, Poole CD, et al. Multivariate models of health-related utility and the fear of hypoglycaemia in people with diabetes. Curr Med Res Opin 2006;22:1523-34

 PubMed Web of Science ®Google Scholar

Matza LS, Boye KS, Yurgin N, et al. Utilities and disutilities for type 2 diabetes treatment-related attributes. Qual Life Res 2007;16:1251-65

 PubMed Web of Science ®Google Scholar

Lane S, Levy AR, Mukherjee J, et al. The impact on utilities of differences in body weight among Canadian patients with type 2 diabetes. Curr Med Res Opin 2014;30:1267-73

 PubMed Web of Science ®Google Scholar

Jönsson L, Bolinder B, Lundkvist J. Cost of hypoglycemia in patients with type 2 diabetes in Sweden. Value Health 2006;9:193-8

 PubMed Web of Science ®Google Scholar

Jaime Caro J, Ozer Stillman I, Danel A, et al. Cost effectiveness of rimonabant use in patients at increased cardiometabolic risk: estimates from a Markov model. J Med Econ 2007;10:239-54

 Google Scholar

Bagust A, Beale S. Modelling EuroQol health‐related utility values for diabetic complications from CODE‐2 data. Health Econ 2005;14:217-30

 PubMed Web of Science ®Google Scholar