TABLE 1.
QW GLP‐1 RA Phase 3 trials included in this review
| Trial | Treatment arms | Background therapies | Study duration | Study type | Randomization ratio | Number of patients | Location(s) |
|---|---|---|---|---|---|---|---|
| Dulaglutide trials | |||||||
| AWARD‐2 28 | Dulaglutide QW (1.5 mg or 0.75 mg) vs insulin glargine QD | Glimepiride and metformin | 78 wk in total (primary endpoint at 52 wk) | Randomized, open‐label | 1:1:1 | 810 | Multinational |
| AWARD‐3 33 | Dulaglutide QW (1.5 mg or 0.75 mg) vs metformin QD (2000 mg) | SOC/≥1 oral anti‐glycaemic medication | 52 wk in total (primary endpoint at 26 wk) | Randomized, double‐blind | 1:1:1 | 807 | Multinational |
| AWARD‐4 29 | Dulaglutide QW (1.5 mg or 0.75 mg) vs insulin glargine QD | Insulin lispro ± metformin | 52 wk in total (primary endpoint at 26 wk) | Randomized, open‐label | 1:1:1 | 884 | Multinational |
| AWARD‐5 35 | Dulaglutide QW (1.5 mg or 0.75 mg) vs sitagliptin QD (100 mg) or placebo | Metformin | 104 wk in total (primary endpoint at 52 wk) | Randomized, open‐label, double‐blind, placebo‐controlled | 2:2:2:1 | 1098 | Multinational |
| AWARD‐7 30 | Dulaglutide QW (1.5 mg or 0.75 mg) vs insulin glargine QD | Insulin lispro | 52 wk in total (primary endpoint at 26 wk) | Randomized, open‐label | 1:1:1 | 577 | Multinational |
| AWARD‐8 47 | Dulaglutide QW (1.5 mg) vs placebo | Glimepiride or sulphonylurea | 24 wk treatment | Randomized, double‐blind | 4:1 | 300 | Multinational |
| AWARD‐9 46 | Dulaglutide QW (1.5 mg) vs placebo | Insulin glargine | 28 wk treatment | Randomized, double‐blind | 1:1 | 300 | Multinational |
| AWARD‐10 48 | Dulaglutide QW (1.5 mg or 0.75 mg) vs placebo | SGLT2i ± metformin | 24 wk treatment | Randomized, double‐blind, placebo‐controlled | 1:1 | 424 | Multinational |
| a REWIND 21 | Dulaglutide QW (1.5 mg) vs placebo | SOC ± basal insulin | Up to 8 y; median follow‐up 5.4 y | Randomized, double‐blind, placebo‐controlled | 1:1 | 9901 | Multinational |
| Exenatide trials | |||||||
| DURATION‐2 36 | Exenatide QW (2 mg) vs sitagliptin QD (100 mg) vs pioglitazone QD (45 mg) | Metformin | 26 wk treatment | Randomized, double‐blind | 1:1:1 | 514 | US, India, Mexico |
| DURATION‐3 31 | Exenatide QW (2 mg) vs insulin glargine QD | Metformin/ metformin + sulphonylurea | 26 wk treatment | Randomized, open‐label | 1:1 | 456 | Multinational |
| DURATION‐4 34 | Exenatide QW (2 mg) vs metformin QD (2000 mg) vs pioglitazone QD (45 mg) vs sitagliptin QD (100 mg) | SOC | 26 wk treatment | Randomized, open‐label | 1:1:1:1 | 820 | Multinational |
| DURATION‐7 49 | Exenatide QW (2 mg) vs placebo | Insulin glargine ± metformin | 28 wk treatment | Randomized, double‐blind, placebo‐controlled | 1:1 | 464 | Multinational |
| DURATION‐8 50 | Exenatide QW (2 mg) + dapagliflozin QD (10 mg) vs exenatide QW (2 mg) vs dapagliflozin QD (10 mg) | Metformin | 28 wk treatment | Randomized, double‐blind, active‐controlled | 1:1:1 | 695 | Multinational |
| a EXSCEL 22 | Exenatide QW (2 mg) vs placebo | Insulin ± up to 2 oral glucose‐lowering drugs | Event‐driven trial; median follow‐up 3.2 y | Randomized, double‐blind, placebo‐controlled | 1:1 | 14 752 | Multinational |
| Semaglutide (subcutaneous injection) trials | |||||||
| SUSTAIN 1 42 | Semaglutide QW (1 mg or 0.5 mg) vs placebo (1 mg or 0.5 mg) | SOC | 30 wk treatment | Randomized, double‐blind | 2:2:1:1 | 387 | Multinational |
| SUSTAIN 2 37 | Semaglutide QW (1 mg or 0.5 mg) vs sitagliptin QD (100 mg) | Metformin, pioglitazone, rosiglitazone, metformin ± pioglitazone or metformin ± rosiglitazone | 56 wk treatment | Randomized, double‐blind | 2:2:1:1 | 1231 | Multinational |
| SUSTAIN 4 32 | Semaglutide QW (1 mg or 0.5 mg) vs insulin glargine QD | Metformin ± sulphonylurea | 30 wk treatment | Randomized, open‐label | 1:1:1 | 1089 | Multinational |
| SUSTAIN 5 44 | Semaglutide QW (1 mg or 0.5 mg) vs placebo (1 mg or 0.5 mg) | Basal insulin ± metformin | 30 wk treatment | Randomized, double‐blind, placebo‐controlled | 2:2:1:1 | 397 | Multinational |
| a SUSTAIN 6 23 | Semaglutide QW (1 mg or 0.5 mg) vs placebo (1 mg or 0.5 mg) | Insulin ± basal or premixed insulin | 109 wk in total (primary endpoint at 104 wk) | Randomized, double‐blind, placebo‐controlled | 1:1:1:1 | 3297 | Multinational |
| SUSTAIN 8 38 | Semaglutide QW (1 mg) vs canagliflozin QD (300 mg) | Metformin | 52 wk treatment | Randomized, double‐blind | 1:1 | 788 | Multinational |
| SUSTAIN 9 51 | Semaglutide QW (1 mg) vs placebo | SGLT2i, metformin, sulphonylurea | 30 wk treatment | Randomized, double‐blind, placebo‐controlled | 1:1 | 302 | Multinational |
| Head‐to‐head trials: QW vs QD or BID | |||||||
| AWARD‐1 39 | Dulaglutide QW (1.5 mg or 0.75 mg) vs exenatide BID (10 µg) vs Placebo | Pioglitazone and metformin | 52 wk in total (primary endpoint at 26 wk) | Randomized, placebo‐controlled | 2:2:2:1 | 978 | Mexico, Argentina, US |
| AWARD‐6 40 | Dulaglutide QW (1.5 mg) vs liraglutide QD (1.8 mg) | Metformin | 26 wk treatment | Randomized, open‐label | 1:1 | 599 | Multinational |
| DURATION‐1 24 , 25 | Exenatide QW (2 mg) vs exenatide BID (10 µg) | Sulphonylurea | 30 wk treatment | Randomized, open‐label, non‐inferiority | 1:1 | 295 | Canada, US |
| DURATION‐5 26 | Exenatide QW (2 mg) vs exenatide BID (10 µg) | SOC or metformin, sulphonylurea, thiazolidinedione, or a combination of these | 24 wk treatment | Randomized, open‐label | 1:1 | 254 | US |
| DURATION‐6 41 | Exenatide QW (2 mg) vs liraglutide QD (1.8 mg) | Sulphonylurea | 26 wk treatment | Randomized, open‐label | 1:1 | 912 | Multinational |
| SUSTAIN 10 52 | Semaglutide QW (1 mg) vs liraglutide QD (1.2 mg) | SGLT2i, metformin, sulphonylurea | 30 wk treatment | Randomized, open‐label | 1:1 | 577 | Multinational |
| Head‐to‐head trials: QW vs QW | |||||||
| SUSTAIN 3 43 | Semaglutide QW (1 mg) vs exenatide QW (2 mg) | Metformin ± thiazolidinedione, ± sulphonylurea | 56 wk treatment | Randomized, open‐label | 1:1 | 813 | Multinational |
| SUSTAIN 7 45 | Semaglutide QW (1 mg or 0.5 mg) vs dulaglutide QW (1.5 mg or 0.75 mg) | Metformin | 40 wk treatment | Randomized, open‐label | 1:1:1:1 | 1201 | Multinational |
Abbreviations: BID, twice‐daily; CVOT, cardiovascular outcomes trial; GLP‐1 RA, glucagon‐like peptide‐1 receptor agonist; QD, once‐daily; QW, once‐weekly; SGLT2i, sodium‐glucose cotransporter‐2 inhibitor; SOC, standard of care; wk, weeks; y, years.
a
These studies are CVOTs, with longer follow‐up times and larger patient populations than the other studies in this table.