Evidence map›Paper›PMID 38066113›Full record

Trial reportNature metabolism2023

Cotadutide promotes glycogenolysis in people with overweight or obesity diagnosed with type 2 diabetes.

Victoria E R Parker, Darren Robertson, Edmundo Erazo-Tapia, Bas Havekes, Esther Phielix, Marlies de Ligt, Kay H M Roumans, Julian Mevenkamp, Folke Sjoberg, Vera B Schrauwen-Hinderling and 10 more

Registry-linked trialOpen access · hybridAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Nature metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT03555994. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
9.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03555994 phase2completed

An Exploratory Phase 2, Randomised, Double-blind, Placebo-controlled, and Open-label Active Comparator Study to Evaluate the Effect of MEDI0382 on Hepatic Glycogen Metabolism in Overweight and Obese Subjects With Type 2 Diabetes Mellitus.

Ran2018Enrolled51Registered outcomes10Posted comparisons5ConditionsType 2 Diabetes MellitusArmsliraglutide, MEDI0382, Placebo
Open the trial in the graph
3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

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  10. The Genetic Blueprint of Obesity: From Pathogenesis to Novel Therapies.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025
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  13. Targeting Metabolism: Innovative Therapies for MASLD Unveiled.International journal of molecular sciences · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 7 institutions in 6 countries.

Victoria E R ParkerResearch and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK. victoria.parker@astrazeneca.com.ORCID 0000-0003-2706-2669
Darren RobertsonResearch and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Edmundo Erazo-TapiaDepartment of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands.
Bas HavekesDepartment of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands.
Esther PhielixDepartment of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands.ORCID 0000-0002-2672-0415
Marlies de LigtDepartment of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands.
Kay H M RoumansDepartment of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands.ORCID 0000-0003-0666-2147
Julian MevenkampDepartment of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands.
Folke SjobergClinical Trial Consultants AB, Uppsala, Sweden.
Vera B Schrauwen-HinderlingDepartment of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands.ORCID 0000-0001-7795-584X
Edvin JohanssonAntaros Medical AB, Mölndal, Sweden.ORCID 0000-0003-2515-2054
Yi-Ting ChangEarly Clinical Development, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Russell EsterlineLate-stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Kenneth SmithCentre of Metabolism, Ageing and Physiology, Royal Derby Hospital Centre, School of Medicine, University of Nottingham, Derby, UK.
Daniel J WilkinsonCentre of Metabolism, Ageing and Physiology, Royal Derby Hospital Centre, School of Medicine, University of Nottingham, Derby, UK.
Lars HansenLate-stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Lars JohanssonAntaros Medical AB, Mölndal, Sweden.ORCID 0000-0001-5954-3497
Philip AmberyLate-stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID 0000-0003-2978-1886
Lutz JermutusResearch and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.ORCID 0000-0001-7660-8467
Patrick SchrauwenDepartment of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands.ORCID 0000-0002-0973-847X
Maastricht University Medical Centre · NLAstraZeneca (United Kingdom) · GBAntaros Medical (Sweden) · SEAstraZeneca (Sweden) · SEAstraZeneca (United States) · USUniversity of Nottingham · GBLinköping University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cotadutide is a dual glucagon-like peptide 1 and glucagon receptor agonist under development for the treatment of non-alcoholic steatohepatitis and type 2 diabetes mellitus (T2DM) and chronic kidney disease. Non-alcoholic steatohepatitis is a complex disease with no approved pharmacotherapies, arising from an underlying state of systemic metabolic dysfunction in association with T2DM and obesity. Cotadutide has been shown to improve glycaemic control, body weight, lipids, liver fat, inflammation and fibrosis. We conducted a two-part, randomized phase 2a trial in men and women with overweight or obesity diagnosed with T2DM to evaluate the efficacy and safety of cotadutide compared with placebo and liraglutide. The primary endpoints were change from baseline to day 28 of treatment in postprandial hepatic glycogen (part A) and to day 35 of treatment in fasting hepatic glycogen (part B) with cotadutide versus placebo. Secondary endpoints in part B were changes in fasting hepatic glycogen with cotadutide versus the mono glucagon-like peptide 1 receptor agonist, liraglutide, and change in hepatic fat fraction. The trial met its primary endpoint. We showed that cotadutide promotes greater reductions in liver glycogen and fat compared with placebo and liraglutide. Safety and tolerability findings with cotadutide were comparable to those of previous reports. Thus, this work provides evidence of additional benefits of cotadutide that could be attributed to glucagon receptor engagement. Our results suggest that cotadutide acts on the glucagon receptor in the human liver to promote glycogenolysis and improve the metabolic health of the liver. ClinicalTrials.gov registration: NCT03555994 .

Indexed as

Diabetes Mellitus, Type 2GlycogenolysisNon-alcoholic Fatty Liver DiseaseFemaleHumansLiraglutideLiver GlycogenMaleObesityOverweightPeptidesReceptors, GlucagoncotadutideLiraglutideLiver GlycogenPeptidesReceptors, Glucagon

Identifiers

PMID38066113
PMCPMC10730390
OpenAlexW4389481378

What Socratic holds

Texttitle and abstract
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.