Once-weekly albiglutide in the management of type 2 diabetes: patient considerations

Figures & data

Table 1 Phase II clinical trials of albiglutide

Study	Population	Duration	Treatment	Change in HbA1c (%)	Change in FPG (mg/dL)	Change in weight (kg)
Seino et al^Citation17	n=215	16 weeks	Placebo	+0.27		−0.67
R, DB, PC, PG, MC, DR	Japanese patients with T2DM		Albiglutide 15 mg weekly	−0.63		+0.40
			Albiglutide 30 mg weekly	−1.29	−42.7*
			Albiglutide 30 mg biweekly	−0.84
Rosenstock et al^Citation16	n=345	16 weeks	Placebo	−0.17±1.01	−1.8±52.3	−0.7±2.9
R, DB, PC, PG, MC, DR	Patients with T2DM inadequately controlled on metformin or diet/exercise		Albiglutide 4 mg weekly	−0.11±1.16	−8.5±56.2	−0.9±1.7
			Albiglutide 15 mg weekly	−0.49±0.74	−13.0±30.3	−0.9±2.9
			Albiglutide 30 mg weekly	−0.87±0.65*	−25.9±36.6*	−1.4±2.4
			Albiglutide 15 mg biweekly	−0.56±0.97	−23.1±43.8	−1.8±2.8
			Albiglutide 30 mg biweekly	−0.79±0.98	−28.5±37.1*	−1.6±2.5
			Albiglutide 50 mg biweekly	−0.79± 1.04*	−23.8±63.4*	−1.1±2.9
			Albiglutide 50 mg monthly	−0.55±1.01	13.0±49.9	−1.1±3.2
			Albiglutide 100 mg monthly	−0.87±0.87*	22.0±63.1*	−1.7±3.6
			Exenatide 5–10 μg BID	−0.54±0.91*	14.4±44.7	−2.4±3.5
Seino et al^Citation14	n=40	29 days	Placebo	−0.30	N/A	N/A
R, SB, PC, PG, MC, DR	Japanese patients with T2DM		Albiglutide 15 mg weekly	−0.58*	−34.6*	−2.86
			Albiglutide 30 mg weekly	−0.57*	−35.7*	−3.58
			Albiglutide 50 mg biweekly	−0.63*	−31.4*	−2.51
			Albiglutide 100 mg monthly	−0.51*	−13.2	−1.44
Matthews et al^Citation15	n=54	9 days	Placebo	N/A	N/A	N/A
R, SB, PC, PG, DR	Patients with T2DM		Albiglutide 9 mg weekly	N/A	−23.8*	N/A
			Albiglutide 16 mg weekly	N/A	−32.5*	N/A
			Albiglutide 32 mg weekly	N/A	−50.7*	N/A

Note:

* P<0.05 compared with placebo. Figures are presented as mean ± standard deviation.

Abbreviations: HbA_1c, glycated hemoglobin; BID, twice daily; DB, double-blind; DR, dose-ranging; FPG, fasting plasma glucose; MC, multicenter; N/A, not applicable; PC, placebo-controlled; PG, parallel-group; R, randomized; SB, single-blind; T2DM, type 2 diabetes mellitus.

Table 2 Phase III clinical trials of albiglutide

Study	Population	Duration	Treatment	Outcomes
Reusch et al^Citation18 Harmony 1 R, DB, PC, PG	n=298 Patients with T2DM inadequately controlled on pioglitazone ± metformin	52 weeks	Placebo + pioglitazone ± metformin Albiglutide 30 mg once weekly + pioglitazone ± metformin	Change in HbA1c from baseline Treatment difference, albiglutide 30 mg versus placebo: −0.75% (95% CI, −0.95, −0.56) Change in FPG from baseline Treatment difference, albiglutide 30 mg versus placebo: −29.5 (95% CI, −39, −20) Change in weight from baseline Treatment difference, albiglutide 30 mg versus placebo: −0.2 kg (95% CI, −1.2, 0.8)
Reinhardt et al^Citation19 Harmony 2 R, DB, PC, PG	n=296 Drug-naïve patients with T2DM inadequately controlled with diet and exercise	52 weeks	Placebo Albiglutide 30 mg once weekly Albiglutide 50 mg once weekly	Change in HbA1c from baseline Treatment difference, albiglutide 30 mg versus placebo: −0.84% (95% CI,−1.11,−0.58) Treatment difference, albiglutide 50 mg versus placebo: −1.04% (95% CI, −1.31, −0.77) Change in FPG from baseline Treatment difference, albiglutide 30 mg versus placebo: −34 mg/dL (95% CI, −46, −22) Treatment difference, albiglutide 50 mg versus placebo: −43 mg/dL (95% CI, −55, −31) Change in weight from baseline Treatment difference, albiglutide 30 mg versus placebo: −0.3 kg (95% CI, −0.9, 1.5) Treatment difference, albiglutide 50 mg versus placebo: −0.2 kg (95% CI, −1.4, 1.0)
Ahrén et al^Citation20 Harmony 3 R, DB, AC, PG	n=999 Patients with T2DM inadequately controlled on metformin	104 weeks	Placebo + metformin Albiglutide 30 mg once weekly + metformin Sitagliptin 100 mg orally once daily + metformin Glimepiride 2–4 mg orally once daily + metformin	Change in HbA1c from baseline Albiglutide versus placebo: −0.91 % (95% CI, −1.16, −0.65) Albiglutide versus sitagliptin: −0.35% (95% CI, −0.53, −0.17) Albiglutide versus glimepiride: −0.27% (95% CI, −0.45, −0.09) Change in FPG from baseline Albiglutide versus placebo: −28 mg/dL (95% CI, −39, −16) Albiglutide versus sitagliptin: −16 mg/dL (95% CI, −24, −8) Albiglutide versus glimepiride: −10 mg/dL (95% CI, −18, −2) Change in weight from baseline Albiglutide versus placebo: −0.2 kg (95% CI, −1.14, 0.73) Albiglutide versus sitagliptin: −0.4 kg (95% CI, −1.01, 0.31) Albiglutide versus glimepiride: −2.4 kg (95% CI, −3.03, −1.71)
Pratley et al^Citation21 Harmony 4 R, OL, PG	n=779 Patients with T2DM inadequately controlled on metformin ± sulfonylurea	52 weeks	Albiglutide 30 mg (option to uptitrate to 50 mg) once weekly Insulin glargine 10 units (option to uptitrate) once daily	Change in HbA1c from baseline Treatment difference, albiglutide versus glargine: 0.11 % (95% CI, −0.04, 0.27) met the prespecified noninferiority margin of 0.3% Change in FPG from baseline Glargine −37 mg/dL versus albiglutide −16 mg/dL (P<0.001) Change in weight from baseline Albiglutide −1.1 kg versus glargine: 1.6 kg, treatment difference 2.6 kg (P<0.000l)
Stewart et al^Citation22 Harmony 5 R, DB, MC	n=685 Patients with T2DM inadequately controlled on metformin (≥ 1,500 mg/day) + glimepiride 4 mg/day	52 weeks	Placebo Albiglutide 30 mg (option to uptitrate to 50 mg) once weekly Pioglitazone 30 mg (option to uptitrate to 45 mg) once daily All patients remained on metformin and glipizide therapy	Change in HbA1c from baseline Treatment difference, albiglutide versus placebo: −0.87% (95% CI, −1.07, −0.68) Treatment difference, albiglutide versus pioglitazone: 0.25% (95% CI, 0.1–0.4), the prespecified noninferiority margin of 0.3% was not met (P=0.27) Change in FPG from baseline Albiglutide −12 mg/dL versus placebo 12 mg/dL (P<0.0001); pioglitazone −31 mg/dL Treatment difference, albiglutide versus pioglitazone favored pioglitazone: 19 mg/dL (95% CI, 11, 27) Change in weight from baseline Albiglutide −0.4 kg versus placebo −0.4 kg; (P=NS), albiglutide versus pioglitazone: −4.9 kg, (P<0.0001)
Fonesca et al^Citation23 Rosenstock et al^Citation24 Harmony 6 OL, AC, PG	n=563 Patients with T2DM inadequately controlled on insulin glargine and oral agents	26 weeks, 52 weeks	Albiglutide 30 mg once weekly + titrated insulin glargine Prandial insulin lispro + titrated insulin glargine Both groups continued on oral agents with the exception of sulfonylureas not allowed	Change in HbA1c from baseline at week 26 Treatment difference, albiglutide versus insulin lispro: −0.16% (−0.32%, 0%) 95% CI, pre-specified non-inferiority margin was met Change in HbA1c from baseline at week 52 Treatment difference, albiglutide versus insulin lispro: −0.17% (95% CI, −0.35, 0.02), prespecified noninferiority was not met Change in FPG from baseline at week 26 Treatment difference, albiglutide versus insulin lispro: −4.9 (95% CI, −13.2, 3.3) Change in FPG from baseline at week 52 Treatment difference, albiglutide versus insulin lispro: −11.2 (95% CI, −21.2, −1.2) Change in weight from baseline at week 26 Treatment difference, albiglutide versus insulin lispro: −1.54 kg (95% CI, −2.09, −1.00) Change in weight from baseline at week 52 Treatment difference, albiglutide versus insulin lispro: −2.61 kg (95% CI, −3.61, −1.62)
Pratley et al^Citation25 Harmony 7 R, DB, OL, PG	n=812 Patients with T2DM inadequately controlled on metformin, thiazolidinedione, sulfonylureas, or any combination of these	32 weeks	Albiglutide titrated to 50 mg once weekly Liraglutide titrated to 1.8 mg once daily	Change in HbA1c from baseline Treatment difference, albiglutide versus liraglutide: −0.21% (95% CI, 0.08, 0.34), prespecified noninferiority was not met Change in FPG from baseline Albiglutide −22.1 mg/dL versus liraglutide −30.4 mg/dL (P=0.50) Change in weight from baseline Albiglutide −0.64 kg, liraglutide −2.9 kg, prespecified noninferiority was not met
Leiter et al^Citation26 Harmony 8 R, DB, PG, MC	n=507 Patients with T2DM and renal insufficiency (eGFR 15 and <90 mL/min/1.73 m^2) inadequately controlled on metformin, thiazolidinedione, sulfonylurea, lifestyle changes or any combination of these	26 weeks	Albiglutide 30 mg (titrated to 50 mg if needed) once weekly Sitagliptin adjusted for renal function	Change in HbA1c from baseline Treatment difference for any degree of renal function, albiglutide versus sitagliptin, −0.32% (95% CI, −0.49, −0.15) Change in FPG from baseline Albiglutide −25.6 mg/dL versus sitagliptin −3.9 mg/dL (P<0.000l) Change in weight from baseline Albiglutide −0.8 kg versus sitagliptin −0.2 kg (P=0.0281)

Abbreviations: HbA_1c, glycated hemoglobin; AC, active control; CI, confidence interval; DB, double-blind; eGFR, estimated glomerular filtration rate; FPG, fasting plasma glucose; MC, multicenter; NS, non significant; OL, open-label; PC, placebo-controlled; PG, parallel-group; R, randomized; T2DM, type 2 diabetes mellitus.

Table 3 Incidence of adverse events in published clinical trials evaluating once-weekly albiglutide dosing

Adverse events n (%)	Albiglutide							Liraglutide	Exenatide	Placebo
	4 mg weekly	9 mg weekly	15 mg weekly	16 mg weekly	30 mg weekly	32 mg weekly	30–50 mg weekly	0.6–1.8 mg/day	5–10 μg BID	N/A
Patients, n	34	14	94	12	91	13	404	408	34	123
Nausea	5 (14.3)	1 (7.1)	10 (11.6)	1 (8.3)	9 (9.9)	2 (15.4)	40 (9.9)	119(29.2)	14 (40.0)	9 (7.3)
Diarrhea	5 (14.3)		3 (3.2)		8 (8.8)		60 (14.9)	55 (13.5)	8 (22.9)	6/111 (5.4)
Vomiting	0	0	5 (5.8)	0	4 (4.3)	2 (15.4)	20 (5.0)	38 (9.3)	6 (17.1)	3 (2.4)
Flatulence			0/8		0/8					1/8 (12.5)
Constipation			3/60 (5.0)		2/62 (3.2)					1/61 (1.6)
Abdominal pain	0		1 (2.4)		0				2 (5.7)	1/58 (1.7)
Headache	6 (17.1)	1 (7.1)	5/34 (14.3)	1 (8.3)	5/29 (16.1)	4 (30.8)	22 (5.4)	22 (5.4)	4 (11.4)	3/72 (4.2)
Dizziness	5 (14.3)	0	2/34 (5.7)	1 (8.3)	2/29 (6.5)	2 (15.4)			3 (8.6)	6/72 (8.3)
Hyperglycemia	6 (17.1)		2/34 (5.7)		2/29 (6.5)				0	7/50 (13.7)
Hypoglycemia	0		2 (4.8)		0				1 (2.9)	2/58 (3.4)
Nasopharyngitis	2 (5.7)		20/86 (23.3)		12/83 (14.4)		24 (5.9)	28 (6.9)	2 (5.7)	11/103 (10.7)
Influenza	1 (2.9)		0/34		3/29 (9.7)				0	0/50
URTI	3 (8.6)		0/34		3/29 (9.7)		42 (10.4)	45(11.0)	4(11.4)	5/50 (9.8)
Cardiac disorder	0		0/34		0/29				2 (5.7)	0/50
Back pain	5 (14.3)		2/34 (5.7)		2/29 (6.5)				0	3/50 (5.9)
Somnolence		0		0		2 (15.4)				0/12
Skin reaction*	1 (2.9)	0	9 (10.4)	2 (16.7)	16 (17.6)	1 (7.7)	28 (6.9)	5 (1.2)	1 (2.9)	6 (4.9)
UTI							25 (6.2)	23 (5.6)
Peripheral edema		0		1 (8.3)		0				2/12 (16.7)
Positive immunogenicity test	1/35(2.9)		2/35 (5.7)		2/31 (6.4)				0	1/51 (2)

Notes:

* Includes injection site bruising, erythema, hemorrhage, hypersensitivity, irrigation, papule, paresthesia, pruritus, rash, and/or urticaria. Data taken from Seino Y et al, Matthews JE et al, Rosenstock J et al, and Seino Y et al.^14–17

Abbreviations: BID, twice daily; NA, not applicable; URTI, upper respiratory tract infection; UTI, urinary tract infection.

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