Health and economic outcomes for exenatide once weekly, insulin, and pioglitazone therapies in the treatment of type 2 diabetes: a simulation analysis

Figures & data

Table 1 Baseline characteristics of the simulation and DURATION trials populations

	Simulation (SD)	NHANESa	DURATION clinical trials – ExQW arm
			Study 1	Study 2	Study 3	Study 5
Sample size	24,878	303	148	160	233	123
Age, year	57.3 (12.5)	58	55	52	58	55
Gender, % male	51.3	46	55	56	52	55
BMI, kg/m^2	33.1 (6.5)	33	35	32	32	33
Weight, kg	93.6 (21.3)	94	102	89	91	94
SBP, mmHg	127.7 (16.0)	132	128	126	135	128
DBP, mmHg	72.3 (11.9)	71	78	–	81	77
FPG, mg/dL	177.3 (33.5)	176	173	166	178	168
A1C, %	8.1 (0.9)	8.1	8.3	8.6	8.3	8.4
TC, mg/dL	198.4 (47.8)	195	174	174	186	196
HDL, mg/dL	48.2 (14.7)	44	44	42.5	46	46
LDL, mg/dL	111.1 (40.4)	107	92	104	104	120
TG, mg/dL	197.6 (146.2)	225	167b	168b	164b	158b
Creatinine, mg/dL	0.89 (0.20)	0.83	–	–	–	–
Diabetes duration, year	9.0 (8.4)	9.6	7	6	8	7
Smokers, %	19.1	18.1	–	–	–	–
History of myocardial infarction, %	7.1	8.1	–	–	–	–
History of stroke, %	3.4	5.4	–	–	–	–
History of CHF, %	4.8	4.7	–	–	–	–

Notes:

a Subjects fulfilling simulation inclusion/exclusion criteria;

b data are geometric, rather than arithmetic, means.

Abbreviations: BMI, body mass index; CHF, congestive heart failure; DBP, diastolic blood pressure; FPG, fasting plasma glucose; HDL, high-density lipoproteins; LDL, low-density lipoproteins; SBP, systolic blood pressure; SD, standard deviation; TC, total cholesterol; TG, triglycerides; creatinine sample is serum.

Figure 1 Changes in A1C (A), weight (B), and systolic blood pressure (C) over 20 years of simulated treatment with high-adherence insulin, PIO, and ExQW versus moderate-adherence insulin.

Abbreviations: A1C, hemoglobin A1c; ExQW, exenatide once weekly; PIO, pioglitazone.

Figure 2 Changes in total cholesterol (A), high- (B) and low-density (C) lipoproteins, and triglycerides (D) over 20 years of simulated treatment with high-adherence insulin, PIO, and ExQW versus moderate-adherence insulin.

Abbreviations: ExQW, exenatide once weekly; PIO, pioglitazone.

Figure 3 Changes relative to moderate-adherence insulin in Kaplan-Meier event rates of cardiovascular and microvascular complications of diabetes after 20 years of simulated treatment with high-adherence insulin, PIO, and ExQW.

Notes: Negative values represent improvements over moderate-adherence insulin. All differences are statistically significant at the 5% level with these exceptions: for myocardial infarction and coronary heart disease death, PIO and ExQW are not significantly different; for stroke, bilateral blindness, and all-cause death, high-adherence insulin and PIO do not significantly differ from moderate-adherence insulin; for congestive heart failure, high-adherence insulin and ExQW do not differ significantly from moderate-adherence insulin; for macroalbuminuria, high-adherence insulin and PIO do not significantly differ; for ESRD, PIO does not significantly differ from high-adherence insulin, nor from moderate-adherence insulin; for macular edema, PIO does not significantly differ from moderate -adherence insulin; for foot ulcer and lower extremity amputation, high-adherence insulin, PIO, and ExQW do not differ amongst themselves, but all are significantly different from moderate-adherence insulin.
Abbreviations: ExQW, exenatide once weekly; PIO, pioglitazone.

Table 2 Total life-years and costs (undiscounted) per initial person for high-adherence insulin, PIO, and ExQW vs moderate-adherence insulin after 5, 10, and 20 years of treatment

Simulation strategy	Total life years	Total costs	Difference vs moderate-adherence insulin
		US$ 2010	Life years	Cost	Cost/life years
5 years
Moderate-adherence insulin	4.77	$36,568	–	–	–
High-adherence insulin	4.77	$36,861	0.004	$293	$56
PIO	4.76	$36,153	−0.003	−$415	−$82
ExQW	4.78	$34,739	0.016	−$1,829	−$409
10 years
Moderate-adherence insulin	9.03	$75,703	–	–
High-adherence insulin	9.05	$76,492	0.016	$789	$73
PIO	9.03	$75,292	−0.005	−$411	−$41
ExQW	9.10	$72,104	0.064	−$3,600	−$455
20 years
Moderate-adherence insulin	15.80	$154,087	–	–
High-adherence insulin	15.87	$156,193	0.075	$2,106	$87
PIO	15.81	$155,281	0.010	$1,195	$69
ExQW	16.06	$149,137	0.264	−$4,950	−$469

Notes: Moderate-adherence insulin, treatment with insulin, initiated once glycemic control lapsed, usually when A1C >8.0%, with adherence set to 76%.

Abbreviations: ExQW, exenatide once weekly; PIO, pioglitazone

Figure 4 QALYs (undiscounted) saved versus moderate-adherence insulin per 1000 simulated patients.

Table 3 Numbers needed-to-treat versus moderate-adherence insulin to avoid a single cardiovascular event

Outcome	Treatment strategy	Number needed-to-treat versus moderate-adherence insulin
		5 years	10 years	20 years
MACE composite	High-adherence insulin	341	128	91
	PIO	149	59	43
	ExQW	74	38	29
Myocardial infarction	High-adherence insulin	345	126	84
	PIO	142	58	38
	ExQW	94	47	33
Stroke	High-adherence insulin	>1,000	>1,000	>1,000
	PIO	>1,000	818	413
	ExQW	295	142	85
Coronary heart disease death	High-adherence insulin	>1,000	429	236
	PIO	>1,000	257	116
	ExQW	407	197	95

Abbreviations: MACE, major adverse cardiovascular event and is a composite measure including myocardial infarction, stroke, and coronary heart disease death; moderate adherence insulin, treatment with insulin, initiated once glycemic control lapsed, usually when A1C > 8.0%, with adherence set to 76%.