2021
DOI: 10.1016/s0140-6736(21)00845-x
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Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial

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Cited by 186 publications
(136 citation statements)
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“…It is clear that OT is effective as a monotherapy to elicit weight loss in DIO rodents ( Deblon et al, 2011 ; Maejima et al, 2011 , 2017 ; Zhang and Cai, 2011 ; Zhang et al, 2011 ; Morton et al, 2012 ; Blevins et al, 2016 ; Roberts et al, 2017 ; Edwards et al, 2021b ), non-human primates ( Blevins et al, 2015 ) and humans ( Zhang et al, 2013 ), but these effects (pre- vs. post-intervention) appear to be modest even after sustained treatments that last 4–8 weeks [≈ 4.9% in DIO mice ( Roberts et al, 2017 ), 8.7% in DIO rats ( Roberts et al, 2017 ), 3.3% in DIO rhesus monkeys ( Blevins et al, 2015 ) and 9.3% humans based on results from a proof of concept study with short duration and small sample size ( Zhang et al, 2013 )]. The average weight loss with the currently FDA approved medications (i.e., orlistat, liraglutide, naltrexone/bupropion, phentermine/topiramate, semaglutide) ranges between 5 and 14.9% ( Allison et al, 2012 ; Apovian et al, 2015 ; Bray et al, 2018 ; Enebo et al, 2021 ).…”
Section: Discussionmentioning
confidence: 99%
“…It is clear that OT is effective as a monotherapy to elicit weight loss in DIO rodents ( Deblon et al, 2011 ; Maejima et al, 2011 , 2017 ; Zhang and Cai, 2011 ; Zhang et al, 2011 ; Morton et al, 2012 ; Blevins et al, 2016 ; Roberts et al, 2017 ; Edwards et al, 2021b ), non-human primates ( Blevins et al, 2015 ) and humans ( Zhang et al, 2013 ), but these effects (pre- vs. post-intervention) appear to be modest even after sustained treatments that last 4–8 weeks [≈ 4.9% in DIO mice ( Roberts et al, 2017 ), 8.7% in DIO rats ( Roberts et al, 2017 ), 3.3% in DIO rhesus monkeys ( Blevins et al, 2015 ) and 9.3% humans based on results from a proof of concept study with short duration and small sample size ( Zhang et al, 2013 )]. The average weight loss with the currently FDA approved medications (i.e., orlistat, liraglutide, naltrexone/bupropion, phentermine/topiramate, semaglutide) ranges between 5 and 14.9% ( Allison et al, 2012 ; Apovian et al, 2015 ; Bray et al, 2018 ; Enebo et al, 2021 ).…”
Section: Discussionmentioning
confidence: 99%
“…Several DACRAs (for example, davalintide (AC2307), KBP-088, KBP-089, KBP-042) have been shown to induce weight loss in animal models of obesity 165 , 240 242 . In addition, a long-acting amylin analogue, cagrilintide, suitable for once-weekly treatment has successfully completed a phase Ib trial (Table 2 ) and is favourably progressing in subsequent studies in combination with semaglutide to what might constitute enhanced chronic efficacy 243 .…”
Section: Novel and Emerging Obesity Therapiesmentioning
confidence: 99%
“…Recent studies suggest that combination therapy (i.e., dual agonists) may be more optimal than monotherapy for sustained weight loss (Frias et al, 2017;Chepurny et al, 2018) (for review see Rodgers et al, 2012). While OT is effective at producing sustained weight loss in DIO rodents (Deblon et al, 2011;Maejima et al, 2011Maejima et al, , 2017Zhang and Cai, 2011;Morton et al, 2012;Blevins et al, 2016;Roberts et al, 2017;Edwards et al, 2021), non-human primates and humans (Zhang et al, 2013), its overall effects on weight loss relative to pre-treatment appears to be relatively modest after 4-8 weeks [≈ 4.9% in DIO mice (Roberts et al, 2017), 8.7% in DIO rats (Roberts et al, 2017), 3.3% in DIO rhesus monkeys , and 9.3% humans (Zhang et al, 2013)], compared to weight loss achieved in response to long-term (20 weeks to ≥ 1 year) studies in humans treated with cagrilintide (amylin analog) and semaglutide [≈ 17.1% of initial body weight (Enebo et al, 2021)] and FDA-approved drugs such as Qsymia (phentermine + topiramate) [≈ 10.9% of initial body weight; (Allison et al, 2012)]. Despite OT treatment being effective at producing sustained reductions in body weight it has limited efficacy in response to long-term treatment when given as a monotherapy.…”
Section: Introductionmentioning
confidence: 99%