The Lancet Diabetes & Endocrinology最新文献

{"title":"Efficacy and safety of monlunabant in adults with obesity and metabolic syndrome: a double-blind, randomised, placebo-controlled, phase 2a trial","authors":"Filip K Knop, George Kunos, Dror Dicker, Jean-Sebastien Paquette, Louis Aronne, Ofir Frenkel, Thomas Holst-Hansen, Karine Lalonde, Jisoo Lee, Glenn Crater","doi":"10.1016/s2213-8587(25)00216-5","DOIUrl":"https://doi.org/10.1016/s2213-8587(25)00216-5","url":null,"abstract":"<h3>Background</h3>Monlunabant, a novel cannabinoid receptor 1 (CB1R) inverse agonist, has shown encouraging weight loss efficacy and tolerability. We aimed to evaluate the efficacy and safety of monlunabant in individuals with obesity and metabolic syndrome.<h3>Methods</h3>This 16-week, randomised, double-blind, placebo-controlled, dose-ranging phase 2a trial, conducted at 25 outpatient research centres in Canada, enrolled adults with obesity and metabolic syndrome. Participants were randomly assigned (1:1:1:1) by means of an interactive response system to once-daily oral tablets of monlunabant 10 mg, 20 mg, 50 mg, or placebo. The participants, site staff, sponsor, and contract research organisation were masked to treatment allocation. The primary endpoint was mean bodyweight (kg) change from baseline at week 16 versus placebo, assessed in all eligible randomised participants, whereas the safety analysis was done in all randomised participants who received at least one dose of trial product. The estimator for the primary estimand was analysed using a mixed model for repeated measures, assuming missing data are missing at random. This trial 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>NCT05891834</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 complete.<h3>Findings</h3>From Sept 8, 2023, to Jan 26, 2024, 409 individuals were screened for eligibility. In total, 243 individuals were randomly assigned to monlunabant 10 mg (n=61), monlunabant 20 mg (n=61), monlunabant 50 mg (n=60), and placebo (n=61); 242 participants received treatment, including 167 (69%) females and 75 (31%) males. 183 (76%) of 242 participants completed the trial: 50 (82%) of 61 received monlunabant 10 mg, 42 (70%) of 60 received monlunabant 20 mg, 34 (57%) of 60 received monlunabant 50 mg, and 57 (93%) of 61 received placebo. At week 16, participants receiving monlunabant showed statistically significant weight loss compared with those receiving placebo (least squares mean difference <em>vs</em> placebo of –6·4 kg [95% CI –8·0 to –4·9] for monlunabant 10 mg, –6·9 kg [–8·5 to –5·3] for monlunabant 20 mg, and –8·0 kg [–9·7 to –6·4] for monlunabant 50 mg). Adverse events were mostly mild to moderate gastrointestinal and psychiatric disorders and were seen in 42 (69%) of 61 participants in the monlunabant 10 mg group, 47 (78%) of 60 participants in the monlunabant 20 mg group, 55 (92%) of 60 participants in the monlunabant 50 mg group, and 42 (69%) of 61 participants in the placebo group. Withdrawals due to adverse events appeared dose-dependent, occurring in eight (13%) participants who ","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"19 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"World Heart Day: diabetes and cardiovascular risk","authors":"","doi":"10.1016/s2213-8587(25)00296-7","DOIUrl":"https://doi.org/10.1016/s2213-8587(25)00296-7","url":null,"abstract":"No Abstract","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"88 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucocorticoid-induced osteoporosis: novel concepts and clinical implications","authors":"Lorenz C Hofbauer, Juliet E Compston, Kenneth G Saag, Martina Rauner, Elena Tsourdi","doi":"10.1016/s2213-8587(25)00251-7","DOIUrl":"https://doi.org/10.1016/s2213-8587(25)00251-7","url":null,"abstract":"Despite advances in targeted therapies, treatment with glucocorticoids remains a mainstay in the management of various immune-mediated diseases. High cumulative doses of exogenous glucocorticoids lead to a spectrum of side-effects, in particular increased fracture risk. Fragility fractures might result in immobility, frequent admission to hospitals, and loss of quality of life. Glucocorticoid excess impairs bone microarchitecture and bone strength and can cause multiple vertebral fractures. Fracture risk at other skeletal sites is also enhanced and triggered by an increased risk for falls. Glucocorticoid-induced osteoporosis results from direct suppression of osteoblast and osteocyte function, a transient stimulation of osteoclast formation and activity, catabolic effects on bone matrix and muscle protein, and metabolic alterations. Assessment of fracture risk using the Fracture Risk Assessment Tool (FRAX) with dual-energy X-ray absorptiometry represents the first diagnostic step; its predictive value can be improved by applying specific adjustments such as the trabecular bone score. This Review highlights how the bone microenvironment responds to supraphysiological glucocorticoid concentrations, and discusses the basis for skeletal fragility and fractures. We review the use and limitations of current and emerging imaging technologies and prediction tools, and discuss bone-forming and antiresorptive treatment strategies and their use to prevent and treat glucocorticoid-induced osteoporosis.","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"154 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to Lancet Diabetes Endocrinol 2025; 13: 699–721","authors":"","doi":"10.1016/s2213-8587(25)00293-1","DOIUrl":"https://doi.org/10.1016/s2213-8587(25)00293-1","url":null,"abstract":"<em>Brandi ML, Pieterman CRC, English KA, et al. Multiple endocrine neoplasia type 1 (MEN1): recommendations and guidelines for best practice.</em> Lancet Diabetes Endocrinol <em>2025;</em> 13: <em>699–721</em>—In this Review, the spelling of Camilla Schalin-Jäntti's name was incorrect in the appendix. This correction has been made to the online version as of Sept 18, 2025.","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"79 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving type 1 diabetes care globally: the importance of medical education","authors":"Brynn E Marks, Jaisree R Iyer, Steven James, Valla Tantayotai, Carine de Beaufort","doi":"10.1016/s2213-8587(25)00253-0","DOIUrl":"https://doi.org/10.1016/s2213-8587(25)00253-0","url":null,"abstract":"No Abstract","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"70 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145072420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semaglutide 7·2 mg: another step towards tackling diseases mediated by obesity","authors":"Naveed Sattar, Michael E J Lean","doi":"10.1016/s2213-8587(25)00262-1","DOIUrl":"https://doi.org/10.1016/s2213-8587(25)00262-1","url":null,"abstract":"No Abstract","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"8 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial","authors":"Sean Wharton, Paula Freitas, Jøran Hjelmesæth, Maria Kabisch, Kristian Kandler, Ildiko Lingvay, Maria Quiroga, Julio Rosenstock, W Timothy Garvey","doi":"10.1016/s2213-8587(25)00226-8","DOIUrl":"https://doi.org/10.1016/s2213-8587(25)00226-8","url":null,"abstract":"<h3>Background</h3>Once-weekly subcutaneous semaglutide 2·4 mg is approved for weight management in people with obesity and related complications; however, some individuals do not reach their therapeutic goals with this dose. We aimed to test the efficacy and safety of a higher dose of semaglutide (7·2 mg) in people with obesity.<h3>Methods</h3>STEP UP was a phase 3b, randomised, double-blind, placebo-controlled and active-controlled trial conducted across 95 hospitals, specialist clinics, and medical centres in 11 countries in adults with BMI 30 kg/m² or greater, without diabetes. Participants were randomly assigned (5:1:1) to receive once-weekly subcutaneous semaglutide 7·2 mg, 2·4 mg, or placebo, with a lifestyle intervention, for 72 weeks. Coprimary endpoints were percentage change in bodyweight and the proportion of participants with a bodyweight reduction of 5% or greater for semaglutide 7·2 mg versus placebo from baseline to week 72 (treatment policy estimand). Confirmatory secondary endpoints were percentage change in bodyweight with 7·2 mg versus 2·4 mg, change in waist circumference (cm), and proportion of participants with bodyweight reductions of 10% or greater, 15% or greater, 20% or greater, and 25% or greater versus placebo, and 20% or greater and 25% or greater versus 2·4 mg. Safety was assessed in all participants who received at least one dose of the trial product. This trial 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>NCT05646706</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 now completed.<h3>Findings</h3>Between Jan 1, 2023, and Nov 26, 2024, 1407 participants were randomly assigned to semaglutide 7·2 mg (n=1005), semaglutide 2·4 mg (n=201), or placebo (n=201). 1037 (73·7%) of 1407 participants were female, the mean age was 47 (SD 12) years, mean bodyweight was 113·0 (24·1) kg, and mean BMI was 39·9 (7·1) kg/m². The mean change in bodyweight was greater with semaglutide 7·2 mg versus 2·4 mg (–18·7% [SE 0·4] <em>vs</em> –15·6% [0·7]; estimated treatment difference [ETD] –3·1% [95% CI –4·7 to –1·6]; p&lt;0·0001) and with semaglutide 7·2 mg versus placebo (–18·7% [0·4] <em>vs</em> –3·9% [0·6]; –14·8% [–16·2 to –13·4]; p&lt;0·0001). Participants in the semaglutide 7·2 mg group were more likely than those in the placebo group to reach bodyweight reductions of 5% or greater (odds ratio 12·1 [95% CI 8·3 to 17·6]; p&lt;0·0001), 10% or greater (14·5 [9·6 to 21·9]; p&lt;0·0001), 15% or greater (20·3 [11·2 to 36·8]; p&lt;0·0001), 20% or greater (27·3 [10·9 to 68·0]; p&lt;0·0001), and 25% or greater (127·4 [36·8 to 441·","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"42 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Once-weekly semaglutide 7·2 mg in adults with obesity and type 2 diabetes (STEP UP T2D): a randomised, controlled, phase 3b trial","authors":"Ildiko Lingvay, Sara J Bergenheim, John B Buse, Paula Freitas, W Timothy Garvey, Nina M Harder-Lauridsen, Julio Rosenstock, Kushal Sahu, Sean Wharton","doi":"10.1016/s2213-8587(25)00225-6","DOIUrl":"https://doi.org/10.1016/s2213-8587(25)00225-6","url":null,"abstract":"<h3>Background</h3>Semaglutide 2·4 mg is approved for weight management in adults with obesity or overweight in the presence of at least one obesity-related complication; however, many people with obesity and type 2 diabetes do not reach their bodyweight reduction goals with this dose. We aimed to investigate the efficacy and safety of a new 7·2 mg maintenance dose of once-weekly subcutaneous semaglutide in people with obesity and type 2 diabetes.<h3>Methods</h3>STEP UP T2D was a randomised, phase 3b, double-blind controlled, three-arm, parallel-group trial conducted at 68 hospitals, specialist clinics, and medical centres in Bulgaria, Canada, Hungary, Poland, Portugal, Slovakia, South Africa, and the USA. Adults aged 18 years or older (BMI ≥30·0 kg/m², HbA_1c 7·0–10·0% [53–86 mmol/mol]) were randomly assigned (3:1:1) to receive once-weekly subcutaneous semaglutide 7·2 mg, 2·4 mg, or placebo, alongside a lifestyle intervention, for 72 weeks. Coprimary endpoints were the percentage change in bodyweight and the proportion of participants reaching a bodyweight reduction of 5% or greater with semaglutide 7·2 mg versus placebo. Confirmatory secondary endpoints were the proportion of participants reaching a bodyweight reduction of 10% or greater, 15% or greater, and 20% or greater, and changes in waist circumference (cm) and HbA_1c (%) with semaglutide 7·2 mg versus placebo. Efficacy was assessed in all randomly assigned participants, and safety was assessed in all randomly assigned participants who received at least one dose of the trial product. This trial 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>NCT05649137</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 now closed and completed.<h3>Findings</h3>Between Jan 4 and May 4, 2023, 512 participants were randomly assigned to receive semaglutide 7·2 mg (n=307), semaglutide 2·4 mg (n=103), or placebo (n=102). 265 (51·8%) of 512 participants were female, the mean age was 56 (SD 10) years, mean bodyweight was 110·1 (22·9) kg, mean BMI was 38·6 (7·1) kg/m², and mean HbA_1c was 8·1% (0·9). Compared with placebo, semaglutide 7·2 mg led to greater reductions in mean bodyweight (−13·2% <em>vs</em> −3·9%; estimated treatment difference [ETD] −9·3% [95% CI −11·0 to −7·7]; p&lt;0·0001); more participants reaching bodyweight reductions of 5% or greater (odds ratio 10·0 [95% CI 6·0 to 16·9]; p&lt;0·0001), 10% or greater (11·3 [5·9 to 21·4]; p&lt;0·0001), 15% or greater (8·1 [3·7 to 17·7]; p&lt;0·0001), and 20% or greater (12·3 [3·0 to 51·0]; p=0·0006); and reduced waist ","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"17 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harmonising terminology for type 1 diabetes: the EDENT1FI lexicon initiative","authors":"Jurgen Vercauteren","doi":"10.1016/s2213-8587(25)00284-0","DOIUrl":"https://doi.org/10.1016/s2213-8587(25)00284-0","url":null,"abstract":"No Abstract","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"86 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type 2 diabetes subtypes classification: a global reckoning with heterogeneity","authors":"Ram Jagannathan, Lisa R Staimez, K M Venkat Narayan","doi":"10.1016/s2213-8587(25)00256-6","DOIUrl":"https://doi.org/10.1016/s2213-8587(25)00256-6","url":null,"abstract":"No Abstract","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"33 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}