Victoria E R Parker 1 , Darren Robertson 1 , Tao Wang 2 , David C Hornigold 1 , Marcella Petrone 1 , Aidan T Cooper 1 , Maximilian G Posch 3 , Tim Heise 4 , Leona Plum-Moerschel 5 , Heike Schlichthaar 6 , Beate Klaus 7 , Philip D Ambery 8 , Juris J Meier 9 , Boaz Hirshberg 2 Show Affiliations »
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CONTEXT: Cotadutide is a dual receptor agonist with balanced glucagon-like peptide-1 and glucagon activity. OBJECTIVE: To evaluate different doses of cotadutide and investigate underlying mechanisms for its glucose-lowering effects. DESIGN/SETTING: Randomized, double-blind, phase 2a study conducted in 2 cohorts at 5 clinical trial sites . PATIENTS: Participants were 65 adult overweight/obese patients with type 2 diabetes mellitus; 63 completed the study; 2 were withdrawn due to AEs . INTERVENTION: Once-daily subcutaneous cotadutide or placebo for 49 days. Doses (50-300 µg) were uptitrated weekly (cohort 1) or biweekly (cohort 2). MAIN OUTCOME MEASURES: Co-primary end points (cohort 1) were percentage changes from baseline to end of treatment in glucose (area under the curve from 0 to 4 hours [AUC0-4h]) post-mixed-meal tolerance test (MMTT) and weight. Exploratory measures included postprandial insulin and gastric emptying time (GET; cohort 2). RESULTS: Patients received cotadutide (cohort 1, n = 26; cohort 2, n = 20) or placebo (cohort 1, n = 13; cohort 2, n = 6). Significant reductions were observed with cotadutide vs placebo in glucose AUC0-4h post MMTT (least squares mean [90% CI], -21.52% [-25.68, -17.37] vs 6.32% [0.45, 12.20]; P < 0.001) and body weight (-3.41% [-4.37, -2.44] vs -0.08% [-1.45, 1.28]; P = 0.002). A significant increase in insulin AUC0-4h post MMTT was observed with cotadutide (19.3 mU.h/L [5.9, 32.6]; P = 0.008) and GET was prolonged on day 43 with cotadutide vs placebo (t½: 117.2 minutes vs -42.9 minutes; P = 0.0392). CONCLUSION: These results suggest that the glucose-lowering effects of cotadutide are mediated by enhanced insulin secretion and delayed gastric emptying . TRIAL REGISTRATION: ClinicalTrials.gov, NCT03244800. © Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
RCT Entities: Population
Interventions
Outcomes
CONTEXT: Cotadutide is a dual receptor agonist with balanced glucagon-like peptide-1 and glucagon activity. OBJECTIVE: To evaluate different doses of cotadutide and investigate underlying mechanisms for its glucose -lowering effects. DESIGN/SETTING: Randomized, double-blind, phase 2a study conducted in 2 cohorts at 5 clinical trial sites. PATIENTS : Participants were 65 adult overweight/obese patients with type 2 diabetes mellitus ; 63 completed the study; 2 were withdrawn due to AEs. INTERVENTION: Once-daily subcutaneous cotadutide or placebo for 49 days. Doses (50-300 µg) were uptitrated weekly (cohort 1) or biweekly (cohort 2). MAIN OUTCOME MEASURES: Co-primary end points (cohort 1) were percentage changes from baseline to end of treatment in glucose (area under the curve from 0 to 4 hours [AUC0-4h]) post-mixed-meal tolerance test (MMTT) and weight. Exploratory measures included postprandial insulin and gastric emptying time (GET; cohort 2). RESULTS: Patients received cotadutide (cohort 1, n = 26; cohort 2, n = 20) or placebo (cohort 1, n = 13; cohort 2, n = 6). Significant reductions were observed with cotadutide vs placebo in glucose AUC0-4h post MMTT (least squares mean [90% CI], -21.52% [-25.68, -17.37] vs 6.32% [0.45, 12.20]; P < 0.001) and body weight (-3.41% [-4.37, -2.44] vs -0.08% [-1.45, 1.28]; P = 0.002). A significant increase in insulin AUC0-4h post MMTT was observed with cotadutide (19.3 mU.h/L [5.9, 32.6]; P = 0.008) and GET was prolonged on day 43 with cotadutide vs placebo (t½: 117.2 minutes vs -42.9 minutes; P = 0.0392). CONCLUSION: These results suggest that the glucose -lowering effects of cotadutide are mediated by enhanced insulin secretion and delayed gastric emptying. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03244800. © Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Entities: Chemical
Disease
Gene
Species
Year: 2020
PMID： 31608926 DOI： 10.1210/clinem/dgz047
Source DB: PubMed Journal: J Clin Endocrinol Metab ISSN： 0021-972X Impact factor: 5.958