Dual glucagon-like peptide-1 and glucagon receptor agonism reduces energy intake in type 2 diabetes with obesity.
Autor: | Golubic R; Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.; Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford, UK., Kennet J; Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK., Parker V; Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK., Robertson D; Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK., Luo D; Statistics, Biometrics Oncology, Oncology R&D, AstraZeneca, Gaithersburg, Maryland, USA., Hansen L; Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA., Jermutus L; Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK., Ambery P; Late Clinical Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Ryaboshapkina M; Translational Science and Experimental Medicine, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Surakala M; R&D IT, AstraZeneca, Cambridge, UK., Laker RC; Bioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA., Venables M; MRC Epidemiology Unit, University of Cambridge, Cambridge, UK., Koulman A; MRC Epidemiology Unit, University of Cambridge, Cambridge, UK., Park A; Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK., Evans M; Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK. |
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Jazyk: | angličtina |
Zdroj: | Diabetes, obesity & metabolism [Diabetes Obes Metab] 2024 Jul; Vol. 26 (7), pp. 2634-2644. Date of Electronic Publication: 2024 Apr 01. |
DOI: | 10.1111/dom.15579 |
Abstrakt: | Aims: To establish which components of energy balance mediate the clinically significant weight loss demonstrated with use of cotadutide, a glucagon-like peptide-1 (GLP-1)/glucagon receptor dual agonist, in early-phase studies. Materials and Methods: We conducted a phase 2a, single-centre, randomized, placebo-controlled trial in overweight and obese adults with type 2 diabetes. Following a 16-day single-blind placebo run-in, participants were randomized 2:1 to double-blind 42-day subcutaneous treatment with cotadutide (100-300 μg daily) or placebo. The primary outcome was percentage weight change. Secondary outcomes included change in energy intake (EI) and energy expenditure (EE). Results: A total of 12 participants (63%) in the cotadutide group and seven (78%) in the placebo group completed the study. The mean (90% confidence interval [CI]) weight change was -4.0% (-4.9%, -3.1%) and -1.4% (-2.7%, -0.1%) for the cotadutide and placebo groups, respectively (p = 0.011). EI was lower with cotadutide versus placebo (-41.3% [-66.7, -15.9]; p = 0.011). Difference in EE (per kJ/kg lean body mass) for cotadutide versus placebo was 1.0% (90% CI -8.4, 10.4; p = 0.784), assessed by doubly labelled water, and -6.5% (90% CI -9.3, -3.7; p < 0.001), assessed by indirect calorimetry. Conclusion: Weight loss with cotadutide is primarily driven by reduced EI, with relatively small compensatory changes in EE. (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.) |
Databáze: | MEDLINE |
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