Comparison of extended release GLP-1 receptor agonist therapy versus sitagliptin in the management of type 2 diabetes

Figures & data

Figure 1 Pharmacokinetics of EQW. Plasma exenatide concentrations following a single dose of EBID (n=39) and multiple doses of EQW (n=31).

Notes: Shading represents exenatide blood level predictions for 2 mg (top boundary) and 0.8 mg (bottom boundary) weekly repeating EQW administrations with the use of superpositioning of single-dose data. The vertical dashed line shows the end of the EQW dosing period in the trial. The horizontal line is the minimally effective level of exenatide demonstrated to reduce fasting plasma glucose concentrations.⁵⁸
Modified from Fineman et al. with kind permission from Springer Science+Business Media: Clin Pharmacokinet, Pharmacokinetics and pharmacodynamics of exenatide extended-release after single and multiple dosing, 2011;50(1):65–74, Fineman M, Flanagan S, Taylor K, et al., figure 2.³²
Abbreviations: BID, twice daily; EBID, exenatide twice daily; EQW, exenatide once weekly; QW, once weekly; SD, standard deviation.

Table 1 Summary of EQW outcomes in the DURATION study program

	DURATION-4^Citation37	DURATION-2^Citation33	DURATION-1^Citation36	DURATION-5^Citation34	DURATION-6^Citation38	DURATION-3^Citation35
Background therapy	D/E alone	MET	D/E alone ± MET, SFU, or TZD (or combos)			MET ± SFU
EQW	2 mg QW	2 mg QW	2 mg QW	2 mg QW	2 mg QW	2 mg QW
Comparator(s)	MET	SITA (100 mg QD)	EBID	EBID	Liraglutide	GLAR
	PIO SITA	PIO (45 mg QD)	(10 μg BID)	(10 μg BID)	(1.8 mg QD)	(10 IU QD)a
Design	DBDD	DBDD	OL	OL	OL	OL
Duration (weeks)	26	26	30	24	26	26
ITT population (N)b	248	160	148	129	911	233
HbA1c (%)
Baseline	8.5	8.6	8.3	8.5	8.5	8.3
LS mean change	−1.5	−1.5	−1.9	−1.6	−1.3	−1.5
HbA1c targets (%)
<7.0%	63	59	71	58	52.3	60
≤6.5%	49	39	45	41	31	35
FPG (mg/dL [mmol/L])
Baseline	178.2 (9.9)	165.6 (9.2)	172.8 (9.6)	172.8 (9.6)	172.8 (9.6)	178.2 (9.9)
LS mean change	−41.4 (−2.3)	32.4 (−1.8)	−41.4 (−2.3)	−34.2 (−1.9)	−32.4 (−1.8)	−37.8 (−2.1)
Weight (kg)
Baseline	88	89.9	101.7	97	91	91.2
LS mean change	−2.0	−2.3	−3.7	−2.3	−2.7	−2.6
SBP (mmHg)
Baseline	128.8	126.4	127.8	130.4	132	135.4
LS mean change	−1.3	−3.6	−4.7	−2.9	−2.5	−3.0

Notes:

a Adjusted to target FPG of 4.0–5.5 mmol/L

b ITT population for the EQW arms.

Abbreviations: DBDD, double-blind double-dummy; D/E, diet and exercise; EBID, exenatide twice daily; EQW, exenatide once weekly; FPG, fasting plasma glucose; GLAR, insulin glargine; HbA_1c, glycated hemoglobin; ITT, intent to treat; LS, least squares; MET, metformin; OL, open-label; PIO, pioglitazone; QW, once weekly; SBP, systolic blood pressure; SITA, sitagliptin; SFU, sulfonylurea; TZD, thiazolidinedione; DURATION, Diabetes Therapy Utilization: Researching Changes in A1c, Weight and Other Factors Through Intervention with Exenatide Once Weekly; QD, once daily; BID, twice daily.

Figure 2 Effects of EQW on glycemia and weight relative to sitagliptin in the DURATION study program.

Abbreviations: EQW, exenatide once weekly; FPG, fasting plasma glucose; HbA_1c, glycated hemoglobin; DURATION, Diabetes Therapy Utilization: Researching Changes in A1c, Weight and Other Factors Through intervention with Exenatide Once Weekly.

Figure 3 Effects of EQW on glycemia and weight relative to comparators in the DURATION trials.

Notes: Data are mean ± SE. *P<0.05; **P<0.001.
Abbreviations: D/E, diet and exercise; EBID, exenatide twice daily; EQW, exenatide once weekly; HbA_1c, glycated hemoglobin; MET, metformin; SFU, sulfonylurea; TZD, thiazolidinedione; DURATION, Diabetes Therapy Utilization: Researching Changes in A1c, Weight and Other Factors Through Intervention with Exenatide Once Weekly.

Table 2 Rates of gastrointestinal adverse events associated with incretin therapies in the DURATION study program

	Nausea (%)	Diarrhea (%)	Vomiting (%)	Constipation (%)
DURATION-1
EQW	26.4	13.5	10.8	10.8
EBID	34.5	13.1	18.6	6.2
DURATION-2
EQW	24	18	11	6
Sitagliptin	10	10	2	2
DURATION-4
EQW	11.3	10.9	NR	8.5
Sitagliptin	3.7	5.5	NR	2.5
DURATION-5
EQW	14.0	9.3	4.7	NR
EBID	35.0	4.1	8.9	NR
DURATION-6
EQW	9.3	6.1	3.7	4.6
Liraglutide	20.7	13.1	10.7	4.9

Abbreviations: EBID, exenatide twice daily; EQW, exenatide once weekly; NR, not reported; DURATION, Diabetes Therapy Utilization: Researching Changes in A1c, Weight and Other Factors Through intervention with Exenatide Once Weekly.

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