Advances in the treatment of type 2 diabetes: impact of dulaglutide

Figures & data

Figure 1 GLP-1-receptor agonists currently approved and in development.

Notes: *Not available in the US. Reproduced from Trujillo JM, Nuffer W. GLP-1 receptor agonists for type 2 diabetes mellitus: recent developments and emerging agents. Pharmacotherapy. 2014;34(11):1174–1186.²¹ With permission of John Wiley and Sons. Copyright © 2014.
Abbreviations: GLP, glucagon-like peptide; SC, subcutaneously; RA, receptor agonist.

Table 1 Comparison of GLP-1-receptor agonists

Drug	Date of FDA approval	Dose	SC administration	Delivery device	Storage	Renal function considerations	Cost (30-day AWP), US$*,^Citation50
Exenatide (Byetta^®)	April 2005	5 μg ×1 month; then 10 μg if tolerated	Twice daily, 30–60 minutes before meal	Multiuse pen (5 μg, 10 μg)	Active pen – room temperature; refrigerate others	CrCl 30–50 mL/min: use caution CrCl <30 mL/min: not recommended	$619.93
Liraglutide(Victoza^®)	January 2010	0.6 mg ×1 week, 1.2 mg ×1 week, then 1.8 mg if tolerated	Once daily	Multiuse pen (three doses in one pen)	Active pen – room temperature; refrigerate others	None	$769.18
Exenatide XR (Bydureon^®)	March 2014	2 mg	Once weekly	Single-use pen (2 mg, requires reconstitution)	Refrigerate; or room temperature for 28 days; room temperature 15 minutes before reconstitution	CrCl 30–50 mL/min: use caution CrCl <30 mL/min: not recommended	$610.22
Albiglutide(Tanzeum^®)	April 2014	30 mg, can increase to 50 mg	Once weekly	Single-use pen (30 mg, 50 mg, requires reconstitution)	Refrigerate; or room temperature for 28 days; room temperature 15 minutes before reconstitution	None	$426.36
Dulaglutide (Trulicity^®)	September 2014	0.75 mg, can increase to 1.5 mg	Once weekly	Single-use pen (0.75 mg, 1.5 mg)	Refrigerate; or room temperature for 14 days	None	$638.16

Note:

* Cost for maximum recommended dose.

Abbreviations: AWP, average wholesale price; CrCl, creatinine clearance; FDA, US Food and Drug Administration; SC, subcutaneous.

Table 2 Efficacy of dulaglutide across randomized controlled trials

Study	Patients (n)	Baseline characteristics	Background treatment (mg)	Study duration for primary efficacy measure (weeks)	Treatment groups	Change in A1c from BL (%)	Achievement of HbA1c <7% (%)	Change in weight from BL (kg)
Wysham et al (AWARD-1)^Citation35	978	Mean age 56 years, A1c 8.1%, BMI 33 kg/m^2, duration of diabetes 9 years	MET (1,500–3,000) + PIO (30–45)	26	DULA 1.5 mg DULA 0.75 mg EXEN 10 μg BID PBO	−1.51 −1.30 −0.99 −0.46	78 66 52 43	−1.30 +0.20 −1.07 +1.24
Giorgino et al(AWARD-2)^Citation36	810	Mean age 57 years, A1c 8.1%, BMI 32 kg/m^2, duration of diabetes 9 years	MET ($1,500) + glimepiride ($4)	52	DULA 1.5 mg DULA 0.75 mg InsGlar#	−1.08 −0.76 −0.63	53 37 31	−1.87 −1.33 +1.44
Umpierrez et al (AWARD-3)^Citation32	807	Mean age 56 years, A1c 7.6%, BMI 33 kg/m^2, duration of diabetes 3 years	None	26	DULA 1.5 mg DULA 0.75 mg MET 1,500–2,000 mg	−0.78 −0.71 −0.56	62 63 54	−2.29 −1.36 −2.22
Blonde et al (AWARD-4)^Citation37	884	Mean age 59.4 years, A1c 8.5%, BMI 32.5 kg/m^2, duration of diabetes 13 years	InsLis ± MET (1,500)	26	DULA 1.5 mg DULA 0.75 mg InsGlar#	−1.64 −1.59 −1.41	68 69 57	−0.87 +0.18 +2.33
Nauck et al(AWARD-5)^Citation33	1,098	Mean age 54 years, A1c 8.1%, BMI 31 kg/m^2, duration of diabetes 7 years	MET ($1,500)	52	DULA 1.5 mg DULA 0.75 mg SITA 100 mg PBO	−1.10 −0.87 −0.39 –	58 49 33 –	−3.03 −2.60 −1.53 –
Dungan et al(AWARD-6)^Citation34	599	Mean age 56.7 years, A1c 8.1%, BMI 33.6 kg/m^2, duration of diabetes 7.2 years	MET ($1,500)	26	DULA 1.5 mg LIRA 1.8 mg	−1.42 −1.36	68 68	−2.90 −3.61

Notes:

# dose uptitrated as needed based on prespecified criteria.

Abbreviations: A1c, glycosylated hemoglobin; BID, bis in die (twice daily); BL, baseline; BMI, body mass index; DULA, dulaglutide; EXEN, exenatide; InsGlar, insulin glargine; InsLis, insulin lispro; LIRA, liraglutide; MET, metformin; PBO, placebo; PIO, pioglitazone; SITA, sitagliptin.

Table 3 Safety of dulaglutide across randomized controlled trials

Study	Treatment group	Discontinuation due to AEs (%)	Overall GI AEs (%)	Nausea (%)	Vomiting (%)	Diarrhea (%)	Total hypoglycemia (%)
Wysham et al (AWARD-1)^Citation35	DULA 1.5 mg	3	47	28	17	11	10.4
	DULA 0.75 mg	1	30	16	6	8	10.7
	EXEN 10 μg BID	3	42	26	11	6	15.9
	PBO	2	18	6	1	6	3.5
Giorgino et al (AWARD-2)^Citation36	DULA 1.5 mg	3.3	NR	15.4	6.6	10.6	55.3
	DULA 0.75 mg	2.9		7.7	3.7	9.2	54.4
	InsGlar	1.9		1.5	1.1	5.7	69.1
Umpierrez et al (AWARD-3)^Citation32	DULA 1.5 mg	4.8	NR	19	8.6	10	12.3
	DULA 0.75 mg	2.2		10.7	5.9	5.2	11.1
	MET 1,500–2,000 mg	3.7		14.6	4.1	13.8	12.7
Blonde et al (AWARD-4)^Citation37	DULA 1.5 mg	7	NR	25.8	12.2	16.6	86.6
	DULA 0.75 mg	5		17.7	10.6	15.7	90.1
	InsGlar	4		3.4	1.7	6.1	90.2
Nauck et al (AWARD-5)^Citation33	DULA 1.5 mg	10.9	41	17	13	15	10.2
	DULA 0.75 mg	7.6	37	14	8	10	5.3
	SITA 100 mg	9.5	23	5	2	3	4.8
Dungan et al (AWARD-6)^Citation34	DULA 1.5 mg	6	36	20	7	12	9
	LIRA 1.8 mg	6	36	18	8	12	6

Abbreviations: AE, adverse effects; BID, bis in die (twice daily); DULA, dulaglutide; EXEN, exenatide; GI, gastrointestinal; InsGlar, insulin glargine; LIRA, liraglutide; NR, not reported; PBO, placebo; SITA, sitagliptin; MET, metformin.

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