Table 3.
HbA1c and body weight change from trials that compared QW GLP‐1 RAs with metformin and other oral anti‐diabetics
| Trial name, time until primary endpoint | Treatment arms | Permitted concomitant treatments | ETD HbA1c, % [95% CI]; P‐value | ETD body weight, kg [95% CI]; P‐value |
|---|---|---|---|---|
| QW GLP‐1 RAs compared with metformin (ETD vs metformin) | ||||
| AWARD‐3 30 , 26 weeks | Dulaglutide 0.75 mg | None | −0.15 [95% CI: NR]; .020 | (−1.36 ± 0.24 a ) |
| Dulaglutide 1.5 mg | −0.22 [−0.36; −0.08]; .002 | (−2.29 ± 0.24 a ) | ||
| Metformin | (−2.22 ± 0.24 a ) | |||
| DURATION‐4 31 , 26 weeks | Exenatide ER 2 mg | None | (−1.53 ± 0.07 a ) | (−2.0 ± 0.2 a ) |
| Metformin | (−1.48 ± 0.07 a ); .62 | (−2.0 ± 0.2 a ); .892 | ||
| QW GLP‐1 RAs compared with DPP4is (ETD vs DPP4i) | ||||
| AWARD‐5 69 , 52 weeks | Dulaglutide 0.75 mg | Metformin | −0.47 [−0.63; −0.31] | −1.07 [95% CI: NR]; <.001 |
| Dulaglutide 1.5 mg | −0.71 [−0.87; −0.55] | −1.50 [95% CI: NR]; <.001 | ||
| Sitagliptin 100 mg (QD) | ||||
| Placebo | ||||
| DURATION‐2 70 , 26 weeks | Exenatide ER 2 mg | Metformin | −0.6 [−0.9; −0.4]; <.0001 | −1.5 [−2.4; −0.7]; .0002 |
| Sitagliptin 100 mg (QD) | ||||
| DURATION‐4 31 , 26 weeks | Exenatide ER 2 mg | None | (−1.53 ± 0.07 a ) | (−2.0 ± 0.2 a ) |
| Sitagliptin 100 mg (QD) | (−1.15 ± 0.08 a ); <.001 | (−0.8 ± 0.3 a ); <.001 | ||
| DURATION‐NEO‐2 26 , 28 weeks | Exenatide ER AI 2 mg | Metformin | −0.38 [−0.70; −0.06]; .021 | 0.1 [−0.7; 0.9]; NS |
| Sitagliptin 100 mg (QD) | ||||
| SUSTAIN 2 71 , 56 weeks | Semaglutide s.c. 0.5 mg | Metformin, pioglitazone, rosiglitazone | −0.77 [−0.92; −0.62]; <.0001 | −2.35 [−3.06; −1.63]; <.0001 |
| Semaglutide s.c. 1 mg | −1.06 [−1.21; −0.91]; <.0001 | −4.20 [−4.91; −3.49]; <.0001 | ||
| Sitagliptin s.c. 100 mg (QD) | ||||
| QW GLP‐1 RAs compared with SGLT2is (ETD vs comparator arm, which included SGLT2i treatment) | ||||
| DURATION‐8 59 , 28 weeks | Exenatide ER 2 mg + Dapagliflozin 10 mg (QD) | Metformin | ||
| Exenatide ER 2 mg | −0.4 [−0.6; −0.1]; .004 b | −1.87 [−2.66; −1.08]; <.001 b | ||
| Dapagliflozin 10 mg (QD) | −0.6 [−0.8; −0.3]; <.001 b | −1.22 [−2.00; −0.44]; .002 b | ||
| SUSTAIN 8 60 |
Semaglutide s.c. 1 mg Canagliflozin 300 mg (QD) |
Metformin | −0.5 [−0.65; −0.33]; <.0001 | −1.06 [−1.76; −0.36]; .0029 |
| SUSTAIN 9 55 , 30 weeks | Semaglutide s.c. 1 mg | SGLT2is ± background ADT besides GLP‐1 RAs DPP4is and AAs | −1.42 [−1.61, −1.24]; <.0001 | −3.81 [−4.70, −2.93]; <.0001 |
| Placebo | ||||
| AWARD‐10 54 , 24 weeks | Dulaglutide 0.75 mg | SGLT2i ± Metformin | −0.66 [−0.84, −0.49]; <.0001 | −0.5 [−1.3, 0.4]; .26 |
| Dulaglutide 1.5 mg | −0.79 [−0.97, −0.61]; <.0001 | −0.9 [−1.8, −0.1]; .028 | ||
| Placebo | ||||
Abbreviations: AA, amylin analogue; ADT, anti‐diabetic treatment; BID, twice‐daily; CI, confidence interval; DPP4i, dipeptidyl peptidase‐4 inhibitor; ETD, estimated treatment difference; exenatide ER, exenatide extended‐release; exenatide ER AI, exenatide ER auto‐injectable; GLP‐1 RA, glucagon‐like peptide‐1 receptor agonist; HbA1c, glycated haemoglobin; NS, non‐significant; OAD, oral anti‐diabetic; QD, once‐daily; QW, once‐weekly; SGLT2i, sodium‐glucose cotransporter‐2 inhibitor; s.c., subcutaneous; SU, sulphonylurea; TZD, thiazolidinedione.
Least squares mean change from baseline ± standard error, P‐value (if stated) is for between‐group interaction.
Combined treatment versus monotherapy.