. 2019 Jul 18;39(8):805–819. doi: 10.1007/s40261-019-00826-0

Table 2.

Clinical efficacy of currently marketed glucagon-like peptide-1 receptor agonists (GLP-1RAs) vs placebo and/or glucose-lowering drugs in phase 3 trials in > 250 patients with type 2 diabetes

Treatment type (study duration)	Comparators	No. of pts	HbA_1c (%)		Weight (kg)
Treatment type (study duration)	Comparators	No. of pts	BL (mean)	Mean change from BL	BL (mean)	Mean change from BL
Exenatide IR 5 or 10 μg twice daily [5]
Add-on to metformin (30 wk)	Exenatide IR 5 μg twice daily	110	8.3	− 0.5^a**	100	− 1.3^a
	Exenatide IR 10 μg twice daily	113	8.2	− 0.9^a**	100	− 2.6^a
	Placebo	113	8.2	− 0.0^a	101	− 0.2^a
Add-on to sulfonylurea (30 wk)	Exenatide IR 5 μg twice daily	125	8.5	− 0.5^a**	95	− 1.1^a
	Exenatide IR 10 μg twice daily	129	8.6	− 0.9^a**	95	− 1.6^a
	Placebo	123	8.7	+ 0.1^a	99	− 0.8^a
Add-on to metformin+ sulfonylurea (30 wk)	Exenatide IR 5 μg twice daily	245	8.5	− 0.7^a**	97	− 1.6^a
	Exenatide IR 10 μg twice daily	241	8.5	− 0.9^a**	98	− 1.6^a
	Placebo	247	8.5	+ 0.1^a	99	− 0.9^a
Add-on to insulin glargine ± metformin and/or thiazolidinedione (30 wk)	Exenatide IR 10 μg twice daily	137	8.3	− 1.7^a**	95	− 1.8^a**
	Placebo	122	8.5	− 1.0^a	94	+ 1.0^a
Add-on to insulin glargine + metformin (30 wk)	Exenatide IR 10 μg twice daily	315	8.3	− 1.1^a	90	− 2.6^a
Add-on to insulin glargine + metformin (30 wk)	Insulin lispro	312	8.2	− 1.1^a	89	+ 1.9^a
Liraglutide 1.2 or 1.8 mg once daily
Monotherapy (1 year) [6]	Liraglutide 1.2 mg/day	251	8.2	− 0.8^††	92	− 2.05^†††
	Liraglutide 1.8 mg/day	246	8.2	− 1.1^†††	93	− 2.45^†††
	Glimepiride 8 mg/day	248	8.2	− 0.5	93	+ 1.1
Add-on to metformin (26 wk) [6]	Liraglutide 1.2 mg/day	240	8.3	− 1.0***^†††	89	− 2.6*^†††
	Liraglutide 1.8 mg/day	242	8.4	− 1.0***^†††	88	− 2.8*^†††
	Placebo	121	8.4	+ 0.1	91	− 1.5
	Glimepiride 4 mg/day	242	8.4	− 1.0	89	+ 1.0
Add-on to glimepiride (26 wk) [6]	Liraglutide 1.2 mg/day	228	8.5	− 1.1***^†††	80	+ 0.3^†††
	Liraglutide 1.8 mg/day	234	8.4	− 1.1***^†††	83	− 0.2^†††
	Placebo	114	8.4	+ 0.2	82	− 0.1
	Rosiglitazone 4 mg/day	231	8.4	− 0.4	81	+ 2.1
Add-on to metformin + rosiglitazone (26 wk) [6]	Liraglutide 1.2 mg/day	177	8.5	− 1.5***	95	− 1.0
	Liraglutide 1.8 mg/day	178	8.6	− 1.5***	95	− 2.0
	Placebo	175	8.4	− 0.5	99	+ 0.6
Add-on to glimepiride + metformin (26 wk) [6]	Liraglutide 1.8 mg/day	230	8.3	− 1.3***^††	86	− 1.8^†††
	Placebo	114	8.3	− 0.2	85	− 0.4
	Insulin glargine	232	8.1	− 1.1	85	+ 1.6
Add-on to metformin (26 wk) [7]	Liraglutide 1.2 mg/day	221	8.4	− 1.2^a†††	94	− 2.7^a
	Liraglutide 1.8 mg/day	218	8.4	− 1.5^a†††	94	− 3.3^a
	Sitagliptin 100 mg/day	219	8.5	− 0.9^a	94	− 0.8^a
Add-on to metformin ± sulfonylurea (26 wk) [7]	Liraglutide 1.8 mg/day	233	8.2	− 1.1^a†††	NR	≈3
Add-on to metformin ± sulfonylurea (26 wk) [7]	Exenatide IR 10 μg twice daily	231	8.1	− 0.8^a	NR	≈3
Lixisenatide 20 μg once daily [9]
Add-on to metformin (24 wk)	Lixisenatide 20 μg/day	161	8.0	− 0.7^a***	90	− 2.7 ^a**
Add-on to metformin (24 wk)	Placebo	162	8.0	− 0.3^a	88	− 1.7^a
Add-on to metformin (24 wk)	Lixisenatide 20 μg/day	318	8.0	− 0.7^a	94	− 2.7^a
Add-on to metformin (24 wk)	Exenatide IR 10 μg twice daily	316	8.0	− 0.9^a†	96	− 3.7^a
Add-on to sulfonylurea ± metformin (24 wk)	Lixisenatide 20 μg/day	573	8.3	− 0.8^a***	82	− 1.6^a**
Add-on to sulfonylurea ± metformin (24 wk)	Placebo	286	8.2	− 0.2^a	84	− 0.8^a
Add-on to pioglitazone ± metformin (24 wk)	Lixisenatide 20 μg/day	323	8.1	− 0.9^a***	93	− 0.1^a
Add-on to pioglitazone ± metformin (24 wk)	Placebo	161	8.1	− 0.4^a	97	+ 0.3^a
Add-on to basal insulin ± metformin (24 wk)	Lixisenatide 20 μg/day	329	8.4	− 0.7 ^a**	87	− 1.6^a
Add-on to basal insulin ± metformin (24 wk)	Placebo	167	8.4	− 0.3^a	89	− 0.4^a
Add-on to basal insulin ± sulfonylurea (24 wk)	Lixisenatide 20 μg/day	154	8.5	− 0.7^a***	66	− 0.5^a
Add-on to basal insulin ± sulfonylurea (24 wk)	Placebo	157	8.5	+ 0.1^a	66	− 0.03^a
Add-on to insulin glargine + metformin ± thiazolidinedione (24 wk)	Lixisenatide 20 μg/day	223	7.6	− 0.7^a**	87	+ 0.3^a*
	Placebo	223	7.6	− 0.4^a	87	+ 1.1^a
Add-on to 1–3 oral glucose-lowering drugs (26 wk)	Lixisenatide 20 μg/day	298	7.8	− 0.6^a	90	− 0.6^a††b
	Insulin glulisine once daily	298	7.7	− 0.5^a	88	+ 1.0^a
	Insulin glulisine three times daily	298	7.8	− 0.8^a‡‡‡	90	+ 1.3^a
Dulaglutide 0.75 or 1.5 mg once weekly [10]
Monotherapy (1 year)	Dulaglutide 0.75 mg/wk	270	7.6	− 0.5^†	NR	− 1.1
	Dulaglutide 1.5 mg/wk	269	7.6	− 0.7^†	NR	− 1.9
	Metformin 1.5–2 g/day	268	7.6	− 0.5	NR	− 2.2^‡
Add-on to metformin (2 years)	Dulaglutide 0.75 mg/wk	302	8.2	− 0.7^†	NR	− 2.4
	Dulaglutide 1.5 mg/wk	304	8.1	− 1.0^†	NR	− 2.9^††
	Sitagliptin 100 mg/day	315	8.1	− 0.3	NR	− 1.7
Add-on to metformin (26 wk)	Dulaglutide 1.5 mg/wk	299	8.1	− 1.4	NR	− 2.9
Add-on to metformin (26 wk)	Liraglutide 1.8 mg/day	300	8.1	− 1.4	NR	− 3.6^‡‡
Add-on to metformin + sulfonylurea (1.5 years)	Dulaglutide 0.75 mg/wk	272	8.2	− 0.6	NR	− 1.5^††
	Dulaglutide 1.5 mg/wk	273	8.1	− 0.9^†	NR	− 2.0^††
	Insulin glargine	262	8.1	− 0.6	NR	+ 1.3
Add-on to glimepiride (24 wk)	Dulaglutide 1.5 mg/wk	239	8.4	− 1.4**	NR	− 0.9
Add-on to glimepiride (24 wk)	Placebo	60	8.4	− 0.1	NR	− 0.2
Add-on to SGLTI ± metformin (24 wk)	Dulaglutide 0.75 mg/wk	141	8.0	− 1.2**	NR	− 2.6
	Dulaglutide 1.5 mg/wk	142	8.0	− 1.3**	NR	− 3.1
	Placebo	140	8.0	− 0.5	NR	− 2.3
Add-on to metformin + pioglitazone (1 year)	Dulaglutide 0.75 mg/wk	280	8.1	− 1.1^†	NR	+ 0.4
	Dulaglutide 1.5 mg/wk	279	8.1	− 1.4^†	NR	− 1.1
	Exenatide IR 10 μg twice daily	276	8.1	− 0.8		− 0.8^‡
Replace previous insulin (1 year)	Dulaglutide 0.75 mg/wk	293	8.4	− 1.4^†	NR	+ 0.9^††
	Dulaglutide 1.5 mg/wk	295	8.5	− 1.5^†	NR	− 0.4^††
	Insulin glargine	296	8.5	− 1.2	NR	+ 2.9
Exenatide ER 2 mg once weekly
Monotherapy or add-on to 1 or 2 oral glucose-lowering drugs (24 wk) [12]	Exenatide ER 2 mg/wk	129	8.5	− 1.6^†††	97	− 2.3
	Exenatide IR 10 μg twice daily	123	8.4	− 0.9	94	− 1.4
Monotherapy or add-on to 1 or 2 oral glucose-lowering drugs (30 wk) [12]	Exenatide ER 2 mg/wk	148	8.3	− 1.9^†	102	− 3.7
	Exenatide IR 10 μg twice daily	147	8.3	− 1.5	102	− 3.6
Add-on to metformin (26 wk) [12]	Exenatide ER 2 mg/wk	160	8.6	− 1.6^†c	89	− 2.3^†d
	Sitagliptin 100 mg/day	166	8.5	− 0.9	87	− 0.8
	Pioglitazone 45 mg/day	165	8.5	− 1.2	86	+ 2.8
Add-on to metformin ± sulfonylurea (26 wk) [12]	Exenatide ER 2 mg/wk	233	8.3	− 1.5^†	91	− 2.6^†
Add-on to metformin ± sulfonylurea (26 wk) [12]	Insulin glargine	223	8.3	− 1.3	91	+ 1.4
Add-on to insulin glargine ± metformin (28 wk; 458) [12]	Exenatide ER 2 mg/wk	230	8.5	− 1.0**	94	− 1.0**
Add-on to insulin glargine ± metformin (28 wk; 458) [12]	Placebo	228	8.5	− 0.2	NR	+ 0.5
Add-on to 1 or 2 oral glucose-lowering drugs (26 wk; 911) [13]	Exenatide ER 2 mg/wk	461	8.5	− 1.3^a	NR	− 2.7^a
	Liraglutide 1.8 mg/day	450	8.4	− 1.5^a	NR	− 3.6^a
Semaglutide 0.5 or 1.0 mg once weekly [15]
Monotherapy (30 wk)	Semaglutide 0.5 mg/wk	128	8.1	− 1.5***	90	− 3.7***
	Semaglutide 1.0 mg/wk	130	8.1	− 1.6***	97	− 4.5***
	Placebo	129	8.0	0	90	− 1.0
Add-on to basal insulin ± metformin (30 wk)	Semaglutide 0.5 mg/wk	132	8.4	− 1.4***	93	− 3.7***
	Semaglutide 1.0 mg/wk	131	8.3	− 1.8***	93	− 6.4***
	Placebo	133	8.4	− 0.1	90	− 1.4
Add-on to metformin and/or thiazolidinedione (56 wk)	Semaglutide 0.5 mg/wk	409	8.0	− 1.3^†††	90	− 4.3^†††
	Semaglutide 1.0 mg/wk	409	8.0	− 1.6^†††	89	− 6.1^†††
	Sitagliptin 100 mg/day	407	8.2	− 0.5	89	− 1.4
Add-on to metformin ± sulfonylurea or other (56 wk)	Semaglutide 1.0 mg/wk	404	8.4	− 1.5^†††	96	− 5.6^†††
Add-on to metformin ± sulfonylurea or other (56 wk)	Exenatide ER	405	8.3	− 0.9	95	− 1.9
Add-on to metformin ± sulfonylurea (30 wk)	Semaglutide 0.5 mg/wk	362	8.1	− 1.2^†††	94	− 3.5^†††
	Semaglutide 1.0 mg/wk	360	8.2	− 1.6^†††	94	− 5.2^†††
	Insulin glargine	360	8.1	− 0.8	93	+ 1.2
Add-on to metformin (40 wk)	Semaglutide 0.5 mg/wk	301	8.3	− 1.5^†††	96	− 4.6 ^†††
Add-on to metformin (40 wk)	Dulaglutide 0.75 mg/wk	299	8.2	− 1.1	96	− 2.3
Add-on to metformin (40 wk)	Semaglutide 1.0 mg/wk	300	8.2	− 1.8 ^†††	96	− 6.5 ^†††
Add-on to metformin (40 wk)	Dulaglutide 1.5 mg/wk	299	8.2	− 1.4	93	− 3.0

For consistency in data between GLP-1RAs, results presented are for the intent-to-treat populations in randomized, controlled trials in > 250 pts and a duration of ≥24 wk reported in the EU [6, 10, 12, 15] and/or USA [5, 7, 9, 13] prescribing information (based on the completeness of the data reported). Trials are limited to those that evaluated approved dosages of GLP-1RA s as monotherapy or as a single addition to existing treatment (+ diet/exercise), and for which statistical data regarding BL and changes in BL for HbA_1c were reported. GLP-1RAs and optimized dosages of insulins were administered subcutaneously; other active comparators were administered orally

BL baseline, HbA_1c glycosylated haemoglobin, NR not reported, pts patients, SGLT2I sodium-glucose cotransporter 2 inhibitor, wk week(s)

*p < 0.05, **p < 0.01, ***p < 0.0001 for GLP-1RA vs placebo

^†p < 0.05, ^††p < 0.01, ^†††p < 0.0001 for GLP-1RA vs active comparator

^‡p < 0.05 vs dulaglutide 0.75 mg/wk; ^‡‡p < 0.05 vs dulaglutide 1.5 mg/wk, ^‡‡‡p = 0.0002 vs lixisenatide 20 μg/day

^aLeast square mean

^bVersus insulin glulisine three times daily

^cp < 0.0001 for exenatide ER vs sitagliptin and p < 0.05 for exenatide ER vs pioglitazone

^dp < 0.05 for exenatide ER vs sitagliptin and p < 0.0001 for exenatide ER vs pioglitazone