Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study

Once‐weekly glucagon‐like peptide‐1 receptor agonist dulaglutide is non‐inferior to once‐daily liraglutide and superior to placebo in Japanese patients with type 2 diabetes: a 26‐week randomized phase III study

“…The safety profile of dulaglutide in this study (Table 2) was similar to that seen in previous GLP‐1 receptor agonist studies 11, 12, 13, 14, 17, 18. The most‐frequently reported adverse event was nasopharyngitis, reported by 12–13% of patients in the active treatment groups.…”

“…This is also the first study in Japanese patients to show non‐inferiority of once‐weekly dulaglutide (0.75 mg) to once‐daily liraglutide (0.9 mg), the maximum doses evaluated in Japanese phase III registration programmes for these compounds. In other once‐weekly GLP‐1 receptor agonist studies DURATION‐6 [26 weeks: exenatide once weekly (AstraZeneca, London, UK)] and HARMONY‐7 [32 weeks: albiglutide (GlaxoSmithKline, Wilmington, DE, USA)], neither exenatide once weekly nor albiglutide demonstrated non‐inferiority to liraglutide (1.8 mg) on HbA1c change from baseline values [LS mean differences 0.21% (95% CI 0.08, 0.33), non‐inferiority margin of 0.25%; and 0.21% (95% CI 0.08, 0.34), non‐inferiority margin of 0.3%, respectively] 17, 18. AWARD‐6 (26 weeks: dulaglutide 1.5 mg) has been the only phase III study to date to demonstrate non‐inferiority to liraglutide (1.8 mg) on HbA1c change from baseline measurements, in mainly Caucasian patients with type 2 diabetes [LS mean difference −0.06% (95% CI −0.19, 0.07), with a non‐inferiority margin of 0.4%] 12.…”

Chronic administration of Glucagon-like peptide-1 receptor agonists improves trabecular bone mass and architecture in ovariectomised mice

“…Our data suggests that LIR is more efficacious in bone than Ex-4, although this might be due to the doses of drugs chosen and/or to a different mechanism of action on bone of LIR and Ex-4. The half-life of Ex-4 is 2.4 hours while LIR has a half-life of 13 hours, therefore Ex-4 would need to be given in regular doses to build up and maintain a high enough concentration in the blood to be therapeutically effective (56). As a result, LIR treatment is formulated as once daily injection in contrast to Ex-4 which is formulated as twice daily injections because of its short half-life (57).…”

“…However, in our study we administrated both treatments once daily and thus this may have contributed to the less pronounced effect of Ex-4 on bone, although the doses for both drugs were chosen because they had osteogenic effects in previous studies (32)(33)(34)(35)37). Clinical studies have shown that LIR is more efficacious than Ex-4 in patients with T2DM, as it induces a significant greater reduction in HbA1c (56). Although our in vitro results do not indicate any major differences in the effects of each drug on bone formation and resorption, we observed a marked difference in the effects of these drugs on calcitonin and sclerostin levels in mouse serum, as Ex-4 stimulates calcitonin and inhibits sclerostin production but not LIR.…”

Impact of Newer Medications for Type 2 Diabetes on Body Weight

“…In an open label study of exenatide 2 mg QW versus liraglutide 1.8 mg, exenatide QW failed to meet noninferiority criteria for A1C reduction (−1.28 vs −1.48 %, respectively), and patients on exenatide had significantly less weight loss than those on liraglutide (−2.68 kg vs −3.58 kg, respectively) [43]. However, more patients in the liraglutide group discontinued the medication due to GI side effects (5.3 %) compared to exenatide QW (2.6 %).…”