The LancetPub Date : 2025-06-20DOI: 10.1016/s0140-6736(25)01185-7
Kirsten Dahl, Søren Toubro, Sohan Dey, Ruben Duque do Vale, Anne Flint, Agnes Gasiorek, Arne Heydorn, Ania M Jastreboff, Cassandra Key, Signe Beck Petersen, Andreas Vegge, Kasper Adelborg
{"title":"Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study","authors":"Kirsten Dahl, Søren Toubro, Sohan Dey, Ruben Duque do Vale, Anne Flint, Agnes Gasiorek, Arne Heydorn, Ania M Jastreboff, Cassandra Key, Signe Beck Petersen, Andreas Vegge, Kasper Adelborg","doi":"10.1016/s0140-6736(25)01185-7","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)01185-7","url":null,"abstract":"<h3>Background</h3>Amycretin is a novel, unimolecular GLP-1 and amylin receptor agonist. The aim of this study was to investigate the safety, tolerability, pharmacokinetics, and effects on bodyweight of subcutaneous amycretin administered over a treatment period of up to 36 weeks in participants with overweight or obesity.<h3>Methods</h3>In this randomised, placebo-controlled, phase 1b/2a study, we investigated the safety, tolerability, pharmacokinetics, and effects on bodyweight of subcutaneous injection of amycretin in participants aged 18–55 years with overweight or obesity (BMI 27·0–39·9 kg/m<sup>2</sup>). The study took place at a single clinical research centre in San Antonio, TX, USA. Participants were randomly allocated to receive amycretin or placebo, with participants and investigators masked to trial product allocation. There were five parts: Part A (single ascending dose); Part B (multiple ascending dose [MAD]—dose escalation), once-weekly amycretin escalated from 0·3 mg to 60 mg for a total treatment duration of 36 weeks; and Parts C, D, and E (MAD—dose response), once-weekly amycretin escalated from 0·3 mg up to maintenance doses of 20 mg for a total treatment duration of 36 weeks, 5 mg for a total of 28 weeks, or 1·25 mg for a total of 20 weeks (maintenance dose sustained for the last 12 weeks). The primary endpoint was the number of treatment-emergent adverse events measured from baseline to end of study (Parts A–E). Secondary endpoints were area under the plasma concentration–time curve, maximum plasma concentration, and relative change in bodyweight from baseline. The safety analysis set comprised all participants exposed to treatment, and the full analysis set comprised all randomly allocated participants. This study is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT06064006</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>.<h3>Findings</h3>Between Sept 15, 2023, and April 24, 2024, 125 participants were randomly allocated to amycretin (n=101) or placebo (n=24). Mean baseline bodyweight was 88·3–99·1 kg across Parts B–E. The most common treatment-emergent adverse events were gastrointestinal, and the majority were mild to moderate in severity and resolved by the end of the study. A large number of participants withdrew from the study, with a high proportion of discontinuations occurring due to reasons unrelated to treatment-emergent adverse events. Estimated mean bodyweight change from baseline was significantly (Parts A–D: p<0·0001; Part E: p=0·0003) higher with amycretin versus placebo in Part B (60 mg, –24·3% <em>vs</em> –1·1%; week 36), P","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334953","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}
The LancetPub Date : 2025-06-19DOI: 10.1016/s0140-6736(25)01111-0
Jing Yuan, Minghui Li, Jing Zhao, Kevin Lu
{"title":"Life expectancy disparities in the USA: the Ten Americas study","authors":"Jing Yuan, Minghui Li, Jing Zhao, Kevin Lu","doi":"10.1016/s0140-6736(25)01111-0","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)01111-0","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329144","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}
The LancetPub Date : 2025-06-19DOI: 10.1016/s0140-6736(25)01110-9
James Fan Wu, Edward Christopher Dee
{"title":"Life expectancy disparities in the USA: the Ten Americas study","authors":"James Fan Wu, Edward Christopher Dee","doi":"10.1016/s0140-6736(25)01110-9","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)01110-9","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329147","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}
The LancetPub Date : 2025-06-19DOI: 10.1016/s0140-6736(25)00635-x
Ali T Taher, Hanny Al-Samkari, Yesim Aydinok, Martin Besser, Audra N Boscoe, Jayme L Dahlin, Gonzalo De Luna, Jeremie H Estepp, Sarah Gheuens, Keely S Gilroy, Andreas Glenthøj, Ai Sim Goh, Varsha Iyer, Antonis Kattamis, Sandra R Loggetto, Susan Morris, Khaled M Musallam, Kareem Osman, Paolo Ricchi, Eduardo Salido-Fiérrez, Stefanie Sacknoff
{"title":"Mitapivat in adults with non-transfusion-dependent α-thalassaemia or β-thalassaemia (ENERGIZE): a phase 3, international, randomised, double-blind, placebo-controlled trial","authors":"Ali T Taher, Hanny Al-Samkari, Yesim Aydinok, Martin Besser, Audra N Boscoe, Jayme L Dahlin, Gonzalo De Luna, Jeremie H Estepp, Sarah Gheuens, Keely S Gilroy, Andreas Glenthøj, Ai Sim Goh, Varsha Iyer, Antonis Kattamis, Sandra R Loggetto, Susan Morris, Khaled M Musallam, Kareem Osman, Paolo Ricchi, Eduardo Salido-Fiérrez, Stefanie Sacknoff","doi":"10.1016/s0140-6736(25)00635-x","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)00635-x","url":null,"abstract":"<h3>Background</h3>Non-transfusion-dependent (NTD) thalassaemia is characterised by ineffective erythropoiesis and haemolytic anaemia, leading to long-term complications, poor quality of life, and early mortality. No oral disease-modifying therapies are approved for β-thalassaemia and no agents are approved for α-thalassaemia. The objective of this study was to evaluate the efficacy and safety of mitapivat, an oral activator of pyruvate kinase, in adults with NTD α-thalassaemia or NTD β-thalassaemia.<h3>Methods</h3>ENERGIZE is a phase 3, double-blind, randomised, placebo-controlled trial followed by an open-label extension conducted at 70 hospitals in 18 countries globally. Participants had to be aged 18 years or older with NTD α-thalassaemia or NTD β-thalassaemia and haemoglobin concentrations of 10 g/dL or lower. Participants were randomly assigned 2:1 to mitapivat or placebo (100 mg orally twice a day for 24 weeks) via a central interactive response technology system using block randomisation, stratified by baseline haemoglobin concentration and thalassaemia genotype. Everyone was masked to the patients' treatment assignment until the study was unblinded for the analysis of the primary endpoint. The primary endpoint was haemoglobin response (≥1·0 g/dL increase from baseline in mean haemoglobin concentration from week 12 through week 24), analysed in all patients who were randomly assigned. Safety was analysed in all patients who received at least one dose of study treatment. This study is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, number <span><span>NCT04770753</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, and is active but not recruiting.<h3>Findings</h3>Between Nov 8, 2021, and March 31, 2023, 235 patients were screened, of whom 194 were enrolled (123 [63%] were female and 71 [37%] were male). 130 patients were randomly assigned to mitapivat and 64 patients to placebo and formed the full analysis set. One patient in each group was randomly assigned but not given treatment and was therefore excluded from the safety analysis set (mitapivat 129 patients and placebo 63 patients). Seven patients in the mitapivat group and one patient in the placebo group discontinued treatment before the end of the 24-week double-blind period. 55 (42%) of 130 patients in the mitapivat group had a haemoglobin response versus one (2%) of 64 in the placebo group (least-squares mean difference 41% [95% CI 32–50], two-sided p<0·0001). Adverse events were reported in 107 (83%) of 129 patients who received mitapivat and 50 (79%) of 63 patients who received placebo. The most commonly reporte","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"607 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329162","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}
The LancetPub Date : 2025-06-19DOI: 10.1016/s0140-6736(25)01112-2
Diana Bowser, Kaili Mauricio, Brielle Ruscitti
{"title":"Life expectancy disparities in the USA: the Ten Americas study","authors":"Diana Bowser, Kaili Mauricio, Brielle Ruscitti","doi":"10.1016/s0140-6736(25)01112-2","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)01112-2","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329146","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}
The LancetPub Date : 2025-06-19DOI: 10.1016/s0140-6736(25)00869-4
Nicolas Kluger, Brian Hurwitz, Bertrand Lefrère
{"title":"Claw hand as a result of Mannerist convention","authors":"Nicolas Kluger, Brian Hurwitz, Bertrand Lefrère","doi":"10.1016/s0140-6736(25)00869-4","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)00869-4","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329176","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}
The LancetPub Date : 2025-06-19DOI: 10.1016/s0140-6736(25)00871-2
Alexis Demas
{"title":"Claw hand as a result of Mannerist convention – Author's reply","authors":"Alexis Demas","doi":"10.1016/s0140-6736(25)00871-2","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)00871-2","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329079","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}
The LancetPub Date : 2025-06-19DOI: 10.1016/s0140-6736(25)01251-6
{"title":"Department of Error","authors":"","doi":"10.1016/s0140-6736(25)01251-6","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)01251-6","url":null,"abstract":"<em>Terkelsen CJ, Freeman P, Dahl JS, et al. SAPIEN 3 versus Myval transcatheter heart valves for transcatheter aortic valve implantation (COMPARE-TAVI 1): a multicentre, randomised, non-inferiority trial.</em> Lancet <em>2025; <strong>405:</strong> 1362–72</em>—In this Article, the last sentence in the Results section should read “At 1 year, patients treated with SAPIEN 3 THVs walked a median of 382 m (IQR 295–450) on the 6-min walk test, whereas patients treated with Myval THVs walked 383 m (300–450; p=0·43).” These corrections have been made to the online version as of June 19, 2025.","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329160","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}
The LancetPub Date : 2025-06-19DOI: 10.1016/s0140-6736(25)01034-7
Yap Boum, Ngozi Adaeze Erondu
{"title":"Reinforcing resilience: confronting the consequences of global malaria aid cuts in Africa","authors":"Yap Boum, Ngozi Adaeze Erondu","doi":"10.1016/s0140-6736(25)01034-7","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)01034-7","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329167","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}