Lancet (London, England)最新文献

{"title":"LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial.","authors":"Shweta Urva, Tamer Coskun, Mei Teng Loh, Yu Du, Melissa K Thomas, Sirel Gurbuz, Axel Haupt, Charles T Benson, Martha Hernandez-Illas, David A D'Alessio, Zvonko Milicevic","doi":"10.1016/S0140-6736(22)02033-5","DOIUrl":"https://doi.org/10.1016/S0140-6736(22)02033-5","url":null,"abstract":"<p><strong>Background: </strong>Treating hyperglycaemia and obesity in individuals with type 2 diabetes using multi-receptor agonists can improve short-term and long-term outcomes. LY3437943 is a single peptide with agonist activity for glucagon, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 1 (GLP-1) receptors that is currently in development for the treatment of type 2 diabetes and for the treatment of obesity and associated comorbidities. We investigated the safety, pharmacokinetics, and pharmacodynamics of multiple weekly doses of LY3437943 in people with type 2 diabetes in a 12-week study.</p><p><strong>Methods: </strong>In this phase 1b, proof-of-concept, double-blind, placebo-controlled, randomised, multiple-ascending dose trial, adults (aged 20-70 years) with type 2 diabetes for at least 3 months, a glycated haemoglobin A<sub>1c</sub> (HbA<sub>1c</sub>) value of 7·0-10·5%, body-mass index of 23-50 kg/m<sup>2</sup>, and stable bodyweight (<5% change in previous 3 months) were recruited at four centres in the USA. Using an interactive web-response system, participants were randomly assigned to receive once-weekly subcutaneous injections of LY3437943, placebo, or dulaglutide 1·5 mg over a 12-week period. Five ascending dose cohorts were studied, with randomisation in each cohort such that a minimum of nine participants received LY3437943, three received placebo, and one received dulaglutide 1·5 mg within each cohort. The top doses in the two highest dose cohorts were attained via stepwise dose escalations. The primary outcome was to investigate the safety and tolerability of LY3437943, and characterising the pharmacodynamics and pharmacokinetics were secondary outcomes. Safety was analysed in all participants who received at least one dose of study drug, and pharmacodynamics and pharmacokinetics in all participants who received at least one dose of study drug and had evaluable data. This trial is registered at ClinicalTrials.gov, NCT04143802.</p><p><strong>Findings: </strong>Between Dec 18, 2019, and Dec 28, 2020, 210 people were screened, of whom 72 were enrolled, received at least one dose of study drug, and were included in safety analyses. 15 participants had placebo, five had dulaglutide 1·5 mg and, for LY3437943, nine had 0·5 mg, nine had 1·5 mg, 11 had 3 mg, 11 had 3/6 mg, and 12 had 3/6/9/12 mg. 29 participants discontinued the study prematurely. Treatment-emergent adverse events were reported by 33 (63%), three (60%), and eight (54%) participants who received LY3437943, dulaglutide 1·5 mg, and placebo, respectively, with gastrointestinal disorders being the most frequently reported treatment-emergent adverse events. The pharmacokinetics of LY3437943 were dose proportional and its half-life was approximately 6 days. At week 12, placebo-adjusted mean daily plasma glucose significantly decreased from baseline at the three highest dose LY3437943 groups (least-squares mean difference -2·8 mmol/L [90% CI -4","PeriodicalId":251261,"journal":{"name":"Lancet (London, England)","volume":" ","pages":"1869-1881"},"PeriodicalIF":168.9,"publicationDate":"2022-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40690262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological interventions for insomnia disorder in adults.","authors":"Matthew J Reid, Andrew S Huhn, Patrick H Finan","doi":"10.1016/S0140-6736(22)02031-1","DOIUrl":"https://doi.org/10.1016/S0140-6736(22)02031-1","url":null,"abstract":"","PeriodicalId":251261,"journal":{"name":"Lancet (London, England)","volume":" ","pages":"1845-1846"},"PeriodicalIF":168.9,"publicationDate":"2022-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40707889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial infection possibly causing autoimmunity: Tropheryma whipplei and membranous nephropathy.","authors":"Thorsten Wiech, Linda Reinhard, Sonia Wulf, Alfio Edoardo Giuffrida, Elisa Longhitano, Rosario Caruso, Hermann-Josef Gröne, Rolf A K Stahl, Peter F Zipfel, Judith Kikhney, Annette Moter, Elion Hoxha, Domenico Santoro","doi":"10.1016/S0140-6736(22)02039-6","DOIUrl":"https://doi.org/10.1016/S0140-6736(22)02039-6","url":null,"abstract":"","PeriodicalId":251261,"journal":{"name":"Lancet (London, England)","volume":" ","pages":"1882-1883"},"PeriodicalIF":168.9,"publicationDate":"2022-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40464588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population ageing in China: crisis or opportunity?","authors":"The Lancet","doi":"10.1016/S0140-6736(22)02410-2","DOIUrl":"https://doi.org/10.1016/S0140-6736(22)02410-2","url":null,"abstract":"","PeriodicalId":251261,"journal":{"name":"Lancet (London, England)","volume":" ","pages":"1821"},"PeriodicalIF":168.9,"publicationDate":"2022-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40707885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut-hormone triple agonists: clinical safety and metabolic benefits.","authors":"Timo D Müller, Matthias H Tschöp","doi":"10.1016/S0140-6736(22)02350-9","DOIUrl":"https://doi.org/10.1016/S0140-6736(22)02350-9","url":null,"abstract":"","PeriodicalId":251261,"journal":{"name":"Lancet (London, England)","volume":" ","pages":"1826-1828"},"PeriodicalIF":168.9,"publicationDate":"2022-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40707886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The UK and Italy make delayed Global Fund pledges.","authors":"Sharmila Devi","doi":"10.1016/S0140-6736(22)02408-4","DOIUrl":"https://doi.org/10.1016/S0140-6736(22)02408-4","url":null,"abstract":"","PeriodicalId":251261,"journal":{"name":"Lancet (London, England)","volume":" ","pages":"1836"},"PeriodicalIF":168.9,"publicationDate":"2022-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40707887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological interventions for insomnia disorder in adults - Authors' reply.","authors":"Andrea Cipriani, Edoardo G Ostinelli, Philip J Cowen","doi":"10.1016/S0140-6736(22)02001-3","DOIUrl":"https://doi.org/10.1016/S0140-6736(22)02001-3","url":null,"abstract":"","PeriodicalId":251261,"journal":{"name":"Lancet (London, England)","volume":" ","pages":"1846"},"PeriodicalIF":168.9,"publicationDate":"2022-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40707890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is prevention at the heart of UK health policy?","authors":"Ferruccio De Lorenzo","doi":"10.1016/S0140-6736(22)02313-3","DOIUrl":"https://doi.org/10.1016/S0140-6736(22)02313-3","url":null,"abstract":"","PeriodicalId":251261,"journal":{"name":"Lancet (London, England)","volume":" ","pages":"1763"},"PeriodicalIF":168.9,"publicationDate":"2022-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40714077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol and health.","authors":"Jakob Manthey, Kevin Shield, Jürgen Rehm","doi":"10.1016/S0140-6736(22)02123-7","DOIUrl":"https://doi.org/10.1016/S0140-6736(22)02123-7","url":null,"abstract":"","PeriodicalId":251261,"journal":{"name":"Lancet (London, England)","volume":" ","pages":"1764-1765"},"PeriodicalIF":168.9,"publicationDate":"2022-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40714078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Department of Error.","authors":"","doi":"10.1016/S0140-6736(22)02307-8","DOIUrl":"https://doi.org/10.1016/S0140-6736(22)02307-8","url":null,"abstract":"","PeriodicalId":251261,"journal":{"name":"Lancet (London, England)","volume":" ","pages":"1766"},"PeriodicalIF":168.9,"publicationDate":"2022-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40487516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}