Effects of glucagon-like peptide-1 receptor agonists on cardiovascular risk factors: A narrative review of head-to-head comparisons.

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Liraglutide 8 endocrinologydiseasesdrugs
dulaglutide 20 endocrinologydiseasesdrugs
Albiglutide 5 endocrinologydiseasesdrugs
Exenatide 10 endocrinologydiseasesdrugs

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Select Drug Character Offset Drug Term Instance
Albiglutide 8339 sizePharmacokineticsStructureSizeShort‐actingContinuous‐actingExendin‐4‐basedGLP‐1‐basedSmall (<5 kDa)Large (~63–73 kDa)Exenatide twice daily14 Albiglutide 22Exenatide twice daily14Albiglutide22Exenatide twice daily14Albiglutide22Lixisenatide18Dulaglutide24Exenatide
Albiglutide 8375 sizePharmacokineticsStructureSizeShort‐actingContinuous‐actingExendin‐4‐basedGLP‐1‐basedSmall (<5 kDa)Large (~63–73 kDa)Exenatide twice daily14Albiglutide22Exenatide twice daily14 Albiglutide 22Exenatide twice daily14Albiglutide22Lixisenatide18Dulaglutide24Exenatide once weekly41Dulaglutide24Exenatide
Albiglutide 8411 (~63–73 kDa)Exenatide twice daily14Albiglutide22Exenatide twice daily14Albiglutide22Exenatide twice daily14 Albiglutide 22Lixisenatide18Dulaglutide24Exenatide once weekly41Dulaglutide24Exenatide once weekly16Dulaglutide24Exenatide
Albiglutide 12221 exenatide 10 μg twice daily24 wkPhase III, randomized, open‐label1:1639MultinationalHARMONY‐752 Albiglutide 50 mg once weekly vs liraglutide 1.8 mg once daily32 wkPhase III, randomized, open‐label, non‐inferiority1:1812MultinationalAWARD‐153Dulaglutide
Albiglutide 12869 lixisenatide 20 μg once daily26 wkRandomized, open‐label1:1404MultinationalRosenstock et al.44 Albiglutide 4, 15, 30 mg once weekly vs albiglutide 15, 30, 50 mg every second week vs albiglutide 50 or 100 mg
Exenatide 8316 sizePharmacokineticsStructureSizeShort‐actingContinuous‐actingExendin‐4‐basedGLP‐1‐basedSmall (<5 kDa)Large (~63–73 kDa) Exenatide twice daily14Albiglutide22Exenatide twice daily14Albiglutide22Exenatide twice daily14Albiglutide22Lixisenatide18Dulaglutide24Exenatide
Exenatide 8352 sizePharmacokineticsStructureSizeShort‐actingContinuous‐actingExendin‐4‐basedGLP‐1‐basedSmall (<5 kDa)Large (~63–73 kDa)Exenatide twice daily14Albiglutide22 Exenatide twice daily14Albiglutide22Exenatide twice daily14Albiglutide22Lixisenatide18Dulaglutide24Exenatide once
Exenatide 8388 (<5 kDa)Large (~63–73 kDa)Exenatide twice daily14Albiglutide22Exenatide twice daily14Albiglutide22 Exenatide twice daily14Albiglutide22Lixisenatide18Dulaglutide24Exenatide once weekly41Dulaglutide24Exenatide once
Exenatide 8451 daily14Albiglutide22Exenatide twice daily14Albiglutide22Exenatide twice daily14Albiglutide22Lixisenatide18Dulaglutide24 Exenatide once weekly41Dulaglutide24Exenatide once weekly16Dulaglutide24Exenatide once weekly16ITCA 65029Liraglutide20ITCA
Exenatide 8487 daily14Albiglutide22Exenatide twice daily14Albiglutide22Lixisenatide18Dulaglutide24Exenatide once weekly41Dulaglutide24 Exenatide once weekly16Dulaglutide24Exenatide once weekly16ITCA 65029Liraglutide20ITCA 65029ITCA 65029Lixisenatide41Semaglutide26,
Exenatide 8523 daily14Albiglutide22Lixisenatide18Dulaglutide24Exenatide once weekly41Dulaglutide24Exenatide once weekly16Dulaglutide24 Exenatide once weekly16ITCA 65029Liraglutide20ITCA 65029ITCA 65029Lixisenatide41Semaglutide26, 42Liraglutide20Liraglutide20Lixisenatide18Semaglutide26,
Exenatide 11571 articleTrialGLP1‐RAs investigatedStudy durationStudy typeRandomization ratioNumber of patientsLocation(s)DURATION‐147 Exenatide 2 mg once weekly vs exenatide 10 μg twice daily30 wkRandomized, open‐label, non‐inferiority1:1303Canada,
Exenatide 11839 daily vs exenatide 10 μg twice daily26 wkRandomized, open‐label1:1464MultinationalDURATION‐549 Exenatide 2 mg once weekly vs exenatide 10 μg twice daily24 wkRandomized, open‐label1:1254USADURATION‐650Exenatide
Exenatide 11955 once weekly vs exenatide 10 μg twice daily24 wkRandomized, open‐label1:1254USADURATION‐650 Exenatide 2 mg once weekly vs liraglutide 1.8 mg once daily26 wkRandomized, open‐label1:1912MultinationalGetGoal‐X51Lixisenatide
Exenatide 14016 vs placebo), open‐label liraglutide4:2:1 (dulaglutide: liraglutide: placebo)492JapanSUSTAIN‐345 Exenatide ER 2.0 mg once weekly vs semaglutide 1.0 mg once weekly56 wkPhase III, randomized, open‐label1:1813Europe,
Liraglutide 1459 differences between GLP‐1RAs in terms of systolic blood pressure (SBP), body weight and total cholesterol. Liraglutide increased heart rate vs its comparators in three separate trials. All GLP‐1RAs reduced glycated haemoglobin
Liraglutide 8556 daily14Albiglutide22Lixisenatide18Dulaglutide24Exenatide once weekly41Dulaglutide24Exenatide once weekly16Dulaglutide24Exenatide once weekly16ITCA 65029 Liraglutide 20ITCA 65029ITCA 65029Lixisenatide41Semaglutide26, 42Liraglutide20Liraglutide20Lixisenatide18Semaglutide26,
Liraglutide 8620 weekly16Dulaglutide24Exenatide once weekly16ITCA 65029Liraglutide20ITCA 65029ITCA 65029Lixisenatide41Semaglutide26, 42 Liraglutide 20Liraglutide20Lixisenatide18Semaglutide26, 42Semaglutidea26, 42aPrecise molecular weight is not included
Liraglutide 8633 once weekly16ITCA 65029Liraglutide20ITCA 65029ITCA 65029Lixisenatide41Semaglutide26, 42Liraglutide20 Liraglutide 20Lixisenatide18Semaglutide26, 42Semaglutidea26, 42aPrecise molecular weight is not included in the cited
Liraglutide 11710 exenatide 10 μg twice daily30 wkRandomized, open‐label, non‐inferiority1:1303Canada, USALEAD‐648 Liraglutide 1.8 mg once daily vs exenatide 10 μg twice daily26 wkRandomized, open‐label1:1464MultinationalDURATION‐549Exenatide
Liraglutide 12733 liraglutide 1.8 mg once daily26 wkPhase III, randomized, open‐label1:1599MultinationalLira‐Lixi43 Liraglutide 1.8 mg once daily vs lixisenatide 20 μg once daily26 wkRandomized, open‐label1:1404MultinationalRosenstock
Liraglutide 15488 significant treatment difference in SBP between two continuous‐acting GLP‐1RAs (Figure 1).45, 58 Liraglutide 0.9 mg once daily decreased SBP significantly more than dulaglutide 0.75 mg once weekly at 26 weeks
Liraglutide 24483 significantly smaller compared with liraglutide 1.8 mg once daily (P < .01 for all).43, 55, 56 Liraglutide 1.8 mg also had a greater impact on HbA1c vs exenatide 10 μg twice daily48 and exenatide 2 mg
dulaglutide 5649 17; lixisenatide once daily18, 19; liraglutide once daily20, 21; albiglutide once weekly22, 23; and dulaglutide once weekly.24, 25 Data from phase III studies of other (currently unapproved) GLP‐1RAs, semaglutide
dulaglutide 7055 for exenatide once weekly in EXSCEL, NCT0114433836). Other CVOTs are ongoing, including REWIND with dulaglutide (NCT01394952),37 HARMONY with albiglutide (NCT02465515)38 and PIONEER‐6 with oral semaglutide (NCT02692716).39
dulaglutide 9317 exenatide) OR (lixisenatide AND liraglutide) OR (lixisenatide AND albiglutide) OR (lixisenatide AND dulaglutide ) OR (lixisenatide AND semaglutide): 3 hits and all 3 included(exenatide [ti] AND liraglutide [ti]) OR
dulaglutide 9492 included(exenatide [ti] AND liraglutide [ti]) OR (exenatide [ti] AND albiglutide [ti]) OR (exenatide [ti] AND dulaglutide [ti]) OR (exenatide [ti] AND semaglutide [ti]): 7 hits, 3 included (4 excluded: 1 detailed glucose fluctuations
dulaglutide 9809 the data were not directly relevant)(liraglutide [ti] AND albiglutide [ti]) OR (liraglutide [ti] AND dulaglutide [ti]) OR (liraglutide [ti] AND semaglutide [ti]): 5 hits and all 5 included(albiglutide [ti] AND dulaglutide
dulaglutide 9918 dulaglutide [ti]) OR (liraglutide [ti] AND semaglutide [ti]): 5 hits and all 5 included(albiglutide [ti] AND dulaglutide [ti]) OR (albiglutide [ti] AND semaglutide [ti]): 0 hits(dulaglutide [ti] AND semaglutide [ti]): 0 hits(exenatide
dulaglutide 9987 included(albiglutide [ti] AND dulaglutide [ti]) OR (albiglutide [ti] AND semaglutide [ti]): 0 hits( dulaglutide [ti] AND semaglutide [ti]): 0 hits(exenatide once weekly [ti] AND twice daily [ti]): 5 hits, 2 included
dulaglutide 13905 weekly vs liraglutide 0.9 mg once daily 26 wk (52‐wk results reported in58) Randomized, blind ( dulaglutide vs placebo), open‐label liraglutide4:2:1 (dulaglutide: liraglutide: placebo)492JapanSUSTAIN‐345Exenatide
dulaglutide 13961 daily 26 wk (52‐wk results reported in58) Randomized, blind (dulaglutide vs placebo), open‐label liraglutide4:2:1 ( dulaglutide : liraglutide: placebo)492JapanSUSTAIN‐345Exenatide ER 2.0 mg once weekly vs semaglutide 1.0 mg
dulaglutide 15558 GLP‐1RAs (Figure 1).45, 58 Liraglutide 0.9 mg once daily decreased SBP significantly more than dulaglutide 0.75 mg once weekly at 26 weeks and 52 weeks (P = .013 and P = .007, respectively),57,
dulaglutide 17936 trials, differences in heart rate observed between GLP‐1RAs were not sustained over time. In AWARD‐1, dulaglutide once weekly significantly increased heart rate at week 26 (+2.8 bpm, both doses) compared with exenatide
dulaglutide 18110 (+2.8 bpm, both doses) compared with exenatide 10 μg twice daily (+1.2 bpm; P < .05 for both dulaglutide 0.75 mg and 1.5 mg once weekly), but at week 52 there were no significant differences between these
dulaglutide 19069 weight from baseline compared with exenatide 2 mg once weekly,50 albiglutide 50 mg once weekly,52 dulaglutide 1.5 mg once weekly54 and lixisenatide 20 μg once weekly,55 in four separate trials (Figure 3).
dulaglutide 23320 exenatide 2 mg once weekly47, 49; P < .01 vs liraglutide 1.8 mg once daily48; P < .01 vs dulaglutide 1.5 mg once weekly and 0.75 mg once weekly53; no between‐treatment statistics were reported vs
dulaglutide 24090 ‡Non‐inferiority P value = .0846 (not meeting predefined non‐inferiority margin). §For both doses of dulaglutide vs exenatide twice daily. ¶Non‐inferiority P value <.001 (meeting predefined non‐inferiority margin).
dulaglutide 24671 daily48 and exenatide 2 mg once weekly,50 but not compared with semaglutide 1.6 mg once weekly42 or dulaglutide 1.5 mg once weekly54 (Figure 5).At least one other measure of glycaemic control (fasting plasma glucose
dulaglutide 29253 treatments (exenatide once weekly, liraglutide once daily, albiglutide once weekly and every second week, dulaglutide once weekly, semaglutide once weekly). For total cholesterol, the only reported significant difference
dulaglutide 33982 exenatide once weekly and lixisenatide14, 16, 18) or human GLP‐1‐based (liraglutide, albiglutide, dulaglutide and semaglutide20, 22, 24) treatments. As the precise signalling pathways between GLP‐1 and CV risk
dulaglutide 35785 the head‐to‐head trials. In the included studies, large GLP‐1RAs (>60 kDa; albiglutide and dulaglutide ) had a reduced effect on body weight compared with smaller GLP‐1RAs (<5 kDa; exenatide twice daily,
dulaglutide 39027 trials (DURATION‐5,49 AWARD‐1,53 Lira‐Lixi43 and SUSTAIN‐345), in which exenatide once weekly,49 dulaglutide ,53 liraglutide43 and semaglutide45 were both statistically and clinically significantly different from
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