TABLE 2.

Summary of Published Once-Weekly GLP-1 RA Pivotal Clinical Trial Data (Efficacy)

Study	Study Design	Treatment Groups	Background Pharmacotherapy
Exenatide ER
DURATION-116	30-week, multicenter, randomized, open-label non-inferiority study (3-day lead-in with exenatide 5 μg BID prior to receiving assigned treatment)	Exenatide ER SC 2 mg QW (n = 148) Exenatide SC 5 μg BID for first 4 weeks, then 10 μg BID for remainder of study (n = 147)	None or metformin, a sulfonylurea, a TZD, or any combination of 2 of these agents
DURATION-217	26-week, multicenter, randomized, double-blind, double-dummy study	Exenatide ER SC 2 mg QW (n = 170) Sitagliptin oral 100 mg QD (n = 172) Pioglitazone oral 45 mg QD (n = 172)	Metformin
DURATION-318	26-week, multicenter, randomized, open-label study	Exenatide ER SC 2 mg QW (n = 233) Insulin glargine SC 10 IU QD adjusted to achieve target glucose of 4.0-5.5 mmol/L (n = 223)	Metformin ≥ 1,500 mg/d ± sulfonylurea
DURATION-419	26-week, multicenter, randomized, placebo-controlled, double-blind, double-dummy study	Exenatide ER SC 2 mg QW (n = 248) Metformin oral 2,000 mg/d (could be increased up to 2,500 mg/d based on glycemic control; n = 246) Pioglitazone oral 45 mg/d (n = 163) Sitagliptin oral 100 mg/d (n = 163)	None
DURATION-520	24-week, multicenter, randomized, open-label study	Exenatide ER SC 2 mg QW (n = 129) Exenatide SC 5 μg BID for first 4 weeks, then 10 μg BID for remainder of study (n = 123)	None or a stable, maximally effective regimen of metformin, sulfonylurea, TZD, or a combination of these medications
DURATION-621	26-week, multicenter, randomized, open-label study	Exenatide ER SC 2 mg QW (n = 461) Liraglutide SC titrated to 1.8 mg QD (n = 450)	Metformin, sulfonylurea, metformin + sulfonylurea, or metformin + pioglitazone
DURATION-722	28-week, multicenter, randomized, double-blind, placebo-controlled, parallel group study	Exenatide ER SC 2 mg QW (n = 231) Placebo (n = 230)	Insulin glargine with/without metformin
DURATION-823	28-week, multicenter, randomized, double-blind study	Exenatide ER SC 2 mg QW + dapagliflozin oral 10 mg QD (n = 231) Exenatide ER SC 2 mg QW (n = 231) plus placebo Dapagliflozin oral 10 mg QD (n = 233) plus placebo	Stable regimen of metformin (≥ 1,500 mg/day)
Dulaglutide
AWARD-124	52-week multicenter, randomized double-blind, placebo-controlled study (placebo-treated patients switched to dulaglutide 0.75 or 1.5 mg QW after 26 weeks; primary endpoint, 26 weeks)	Dulaglutide SC 0.75 mg QW (n = 280) Dulaglutide SC 1.5 mg QW (n =279) Exenatide SC 5 μg BID for first 4 weeks, then 10 μg BID for remainder of study (n = 276) Placebo (n = 141)	Metformin (1,500-3,000 mg/d) and pioglitazone (30-45 mg/d)
AWARD-225	78-week, multicenter, randomized, open-label (blind to dulaglutide dose) study (primary endpoint, 52 weeks)	Dulaglutide SC 0.75 mg QW (n = 272) Dulaglutide SC 1.5 mg QW (n = 273) Insulin glargine SC 10 IU QD adjusted to achieve target glucose < 5.6 mmol/L (n = 262)	Metformin (1,500 mg/d) and glimepiride (4 mg/d); both could be increased to maximum locally approved doses
AWARD-326	52-week, multicenter, randomized, double-blind, double-dummy non-inferiority study (primary endpoint, 26 weeks)	Dulaglutide SC 0.75 mg QW (n = 270) Dulaglutide SC 1.5 mg QW (n = 269) Metformin oral 2,000 mg/d (at least 1,500 depending on tolerability; n = 268)	None
AWARD-427	52-week, multicenter, randomized, open-label noninferiority study (primary endpoint, 26 weeks)	Dulaglutide SC 0.75 mg QW (n = 293) Dulaglutide SC 1.5 mg QW (n = 295) Insulin glargine SC adjusted based on a treat-to-target strategy (n = 296)	Prandial insulin lispro ± metformin ≥ 1,500 mg/d
AWARD-528	104-week, multicenter, randomized, double-blind, placebo-controlled study; randomized dose-finding period for dulaglutide followed by randomized fixed-dose period (primary endpoint, 52 weeks)	Dulaglutide SC 0.75 mg QW (n = 302) Dulaglutide SC 1.5 mg QW (n = 304) Sitagliptin, oral 100 mg QD (n = 315) Placebo, replaced with sitagliptin 100 mg QD after 26 weeks (n = 177)	Metformin ≥ 1,500 mg/d
AWARD-629	26-week, multicenter, randomized, open-label non-inferiority study	Dulaglutide SC 1.5 mg QW (n = 299) Liraglutide SC 1.8 mg QD (n = 300)	Metformin ≥ 1,500 mg/d
AWARD-830	24-week, multicenter, randomized, double-blind, placebo-controlled study	Dulaglutide SC 1.5 mg QW (n = 240) Placebo (n = 60)	Glimepiride
AWARD-931	28-week, multicenter, randomized, double-blind, placebo-controlled study	Dulaglutide SC 1.5 mg QW (n = 150) Placebo (n = 150)	Insulin glargine once-daily titrated to target ± metformin
Semaglutide
SUSTAIN-132	30-week, multicenter, randomized, double-blind, placebo-controlled study	Semaglutide SC 0.5 mg QW (n = 128) Semaglutide SC 1.0 mg QW (n = 130) Placebo (n = 129)	None
SUSTAIN-233	56-week, multicenter, randomized, double-blind, double-dummy, placebo-controlled study	Semaglutide SC 0.5 mg QW (n = 409) Semaglutide SC 1.0 mg QW (n = 409) Sitagliptin oral 100 mg QD (n = 407)	Metformin (≥ 1,500 mg), pioglitazone (≥ 30 mg), rosiglitazone (≥ 4 mg), or a combination of either metformin + pioglitazone or metformin + rosiglitazone
SUSTAIN-334	56-week, multicenter, randomized, open-label study	Semaglutide SC 1.0 mg QW (n = 404) Exenatide ER SC 2.0 mg QW (n = 405)	1-2 OADs, including metformin, sulfonylureas, and/or TZDs
SUSTAIN-435	30-week, multicenter, randomized, open-label non-inferiority study	Semaglutide SC 0.5 mg QW (n = 362) Semaglutide SC 1.0 mg QW (n = 360) Insulin glargine SC 10 IU QD adjusted to achieve target glucose of 4.0-5.5 mmol/L (n = 360)	Metformin ± sulfonylurea
SUSTAIN-536	30-week, multicenter randomized, double-blind, placebo-controlled study	Semaglutide SC 0.5 mg QW (n = 132) Semaglutide SC 1.0 mg QW (n = 131) Placebo (n = 133)	Basal insulin ± metformin
SUSTAIN-737	40-week, randomized, open-label study	Semaglutide SC 0.5 mg QW (n = 301) Semaglutide SC 1.0 mg QW (n = 300) Dulaglutide SC 0.75 mg QW (n = 299) Dulaglutide SC 1.5 mg QW (n = 299)	Metformin (≥ 1,500 mg or maximum tolerated dose)

BID = twice daily; ER = extended-release; GLP-1 RA = glucagon-like peptide-1 receptor agonist; IU = international unit; OAD = oral antidiabetic drug; QD = once daily; QW = once weekly; SC = subcutaneous; TZD = thiazolidinedione.