Lixin Guo, Xiaolei Bao, Kuo-Chin Huang, Kristoffer Jensen Kolnes, Christian Laugesen, Yibing Lu, Bifen Luo, Guoyue Yuan, Robert F Kushner
{"title":"Efficacy and safety of once-weekly semaglutide 2·4 mg in Chinese adults with overweight or obesity (STEP 12): a randomised, double-blind, placebo-controlled, multicentre, phase 3b trial.","authors":"Lixin Guo, Xiaolei Bao, Kuo-Chin Huang, Kristoffer Jensen Kolnes, Christian Laugesen, Yibing Lu, Bifen Luo, Guoyue Yuan, Robert F Kushner","doi":"10.1016/S2213-8587(26)00133-6","DOIUrl":"10.1016/S2213-8587(26)00133-6","url":null,"abstract":"<p><strong>Background: </strong>Semaglutide 2·4 mg is a GLP-1 receptor agonist that reduces bodyweight, and provides other cardiometabolic benefits, among people with a BMI at least 30 kg/m<sup>2</sup> or at least 27 kg/m<sup>2</sup> and with weight-related comorbidities. This trial aimed to evaluate the efficacy, tolerability, and safety of semaglutide 2·4 mg in adults from mainland China and Taiwan with overweight or obesity according to locally defined, BMI thresholds.</p><p><strong>Methods: </strong>This completed randomised, double-blind, placebo-controlled, multicentre, two-armed, parallel-group, phase 3b trial (STEP 12) was conducted at 19 sites across mainland China and Taiwan. Adults with a BMI of 24-<28 kg/m<sup>2</sup> and at least one weight-related comorbidity, or a BMI of 28-<30 kg/m<sup>2</sup>, with or without type 2 diabetes, were randomly assigned (2:1) to once-weekly subcutaneous semaglutide 2·4 mg or placebo, plus lifestyle intervention, for 44 weeks. Randomisation was performed by the study sponsor using the Randomisation Trial Supplies Management System. Coprimary endpoints were percentage change in bodyweight and the proportion of participants achieving at least 5% bodyweight reduction. Safety was analysed descriptively in all participants who received the trial intervention. Missing data at week 44 were imputed with washout multiple imputation. This study is registered with ClinicalTrials.gov, NCT06041217, and is completed.</p><p><strong>Findings: </strong>Between Sept 15, 2023, and May 7, 2025, of 254 screened participants, 161 (66·5%) of 242 participants were randomly assigned to semaglutide 2·4 mg and 81 (33·5%) to placebo; 121 (50·0%) participants were female, and 47 (19·4%) participants had type 2 diabetes. Bodyweight reduction was greater with semaglutide versus placebo (-12·1% [SE 0·6] vs -2·2% [0·8]; estimated treatment difference -9·9 percentage points [95% CI -11·8 to -8·0]; p<0·0001), with a greater proportion of participants achieving at least 5% bodyweight reduction (80·5% vs 24·4%; odds ratio [OR] 14·8 [95% CI 7·4 to 29·6]; p<0·0001). Adverse events were reported in 141 (87·6%) of 161 participants in the semaglutide 2·4 mg group and 61 (75·3%) of 81 participants in the placebo group, with gastrointestinal disorders being the most common.</p><p><strong>Interpretation: </strong>Semaglutide 2·4 mg provided a superior reduction in bodyweight versus placebo in Chinese adults with overweight or obesity. The safety profile was consistent with the known profile of semaglutide.</p><p><strong>Funding: </strong>Novo Nordisk A/S.</p><p><strong>Translation: </strong>For the Mandarin translation of the abstract see Supplementary Materials section.</p>","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":" ","pages":"805-817"},"PeriodicalIF":36.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148708293","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}
Johannes F E Mann, Sunil V Badve, Florian M M Baeres, Nicolas Belmar, Kirstine Brown-Frandsen, John B Buse, Helen M Colhoun, John E Deanfield, Mads D M Engelmann, G Kees Hovingh, Thomas Idorn, A Michael Lincoff, Ildiko Lingvay, Kenneth W Mahaffey, Darren K McGuire, Richard E Pratley, Søren Rasmussen, Peter Rossing, Naveed Sattar, Katherine R Tuttle, Vlado Perkovic
{"title":"Effect of semaglutide on kidney outcomes in the SELECT, FLOW, and SOUL trials: a prespecified pooled analysis.","authors":"Johannes F E Mann, Sunil V Badve, Florian M M Baeres, Nicolas Belmar, Kirstine Brown-Frandsen, John B Buse, Helen M Colhoun, John E Deanfield, Mads D M Engelmann, G Kees Hovingh, Thomas Idorn, A Michael Lincoff, Ildiko Lingvay, Kenneth W Mahaffey, Darren K McGuire, Richard E Pratley, Søren Rasmussen, Peter Rossing, Naveed Sattar, Katherine R Tuttle, Vlado Perkovic","doi":"10.1016/S2213-8587(26)00134-8","DOIUrl":"10.1016/S2213-8587(26)00134-8","url":null,"abstract":"<p><strong>Background: </strong>The GLP-1 receptor agonist semaglutide reduces clinically important kidney outcomes in people with type 2 diabetes and chronic kidney disease (CKD). We aimed to assess the pooled effects of semaglutide on kidney outcomes in prespecified analyses of participant-level data from the diverse populations of the SELECT, FLOW, and SOUL randomised placebo-controlled trials.</p><p><strong>Methods: </strong>Participants with CKD (FLOW) or atherosclerotic cardiovascular disease (SELECT and SOUL) were randomly assigned semaglutide (once-weekly subcutaneous 1·0 mg [FLOW], once-weekly subcutaneous 2·4 mg [SELECT], or once-daily oral 14 mg [SOUL]) or matching placebo, added to standard of care. The primary outcome in this pooled analysis was time to first occurrence of a kidney composite, defined as onset of persistent 50% or greater reduction in estimated glomerular filtration rate (eGFR), kidney failure (persistent eGFR <15 mL/min per 1·73 m<sup>2</sup>, or initiation of kidney replacement therapy), kidney-related death, or cardiovascular-related death. Safety was also assessed.</p><p><strong>Findings: </strong>The pooled participants from the trials (N=30 787) had a mean follow-up of 39·5-47·5 months. Among participants assigned to semaglutide, 973 first events of the primary kidney composite occurred compared with 1134 first events for placebo (hazard ratio [HR] 0·84 [95% CI 0·77-0·91]). First events of a narrower secondary kidney composite (excluding cardiovascular-related death from the primary outcome) were also reduced with semaglutide versus placebo (347 and 416, respectively; 0·80 [0·69-0·92]). Safety outcomes were overall similar between groups, and in line with other GLP-1 receptor agonist trials. Serious adverse events were numberically lower with semaglutide than with placebo.</p><p><strong>Interpretation: </strong>Data pooled from three large phase 3 trials suggest that semaglutide reduces the risk of major kidney outcomes in a broad population with cardio-kidney-metabolic disease while having a favourable risk-benefit profile. In people with cardio-kidney-metabolic disease, with and without diabetes, semaglutide (oral or injected) prevents kidney-related and cardiovascular complications and induces adverse events in line with GLP-1 receptor agonist studies, regardless of baseline characteristics within the cardio-kidney-metabolic spectrum. This was a participant-level analysis conducted in a large database of three randomised controlled trials of similar design and examining the same treatment, but there were some differences in participants' baseline characteristics, and in the dose and route of administration of treatment. This pooled analysis adds evidence for the benefit of GLP-1 receptor agonists in general, and semaglutide in particular, in a broad population of people with cardio-kidney-metabolic disease, suggesting that the benefit of semaglutide might not be explained only by its glycaemic effects, weight","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":" ","pages":"818-830"},"PeriodicalIF":36.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148690220","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}
Anna R Kahkoska, Peter K Yang, Joshua J Neumiller, Anastasia-Stefania Alexopoulos, Nancy A Allen, Naomi S Chaytor, Michael Fang, Jonathan A Golding, Sanjay Kalra, David S Martins, Camille M Mba, Jean Claude Mbanya, Alan J Sinclair, Heather L Stuckey, Medha Munshi
{"title":"Type 1 diabetes in older populations.","authors":"Anna R Kahkoska, Peter K Yang, Joshua J Neumiller, Anastasia-Stefania Alexopoulos, Nancy A Allen, Naomi S Chaytor, Michael Fang, Jonathan A Golding, Sanjay Kalra, David S Martins, Camille M Mba, Jean Claude Mbanya, Alan J Sinclair, Heather L Stuckey, Medha Munshi","doi":"10.1016/S2213-8587(26)00154-3","DOIUrl":"10.1016/S2213-8587(26)00154-3","url":null,"abstract":"<p><p>In recent decades, life expectancy among people with type 1 diabetes has improved substantially in many high-income countries and well resourced health-care settings, highlighting persistent global inequities in survival for people with type 1 diabetes living in low-income and middle-income countries. Simultaneously, the growing proportion of individuals living into older adulthood in some settings highlights the need to look beyond insulin and glucose to consider the global health systems and wider determinants of health that shape health and longevity in the setting of type 1 diabetes. The goal of this Review is to integrate the psychosocial, environmental, and societal challenges associated with ageing and type 1 diabetes including disease burden, health system and organisational responses, self-care, and caregiver support. Additionally, we identify key research gaps for the future, considering the life course of people with type 1 diabetes in the context of where they live.</p>","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":" ","pages":"856-866"},"PeriodicalIF":36.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148632311","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}
Linong Ji, Malik Benamar, Viswanathan Mohan, Laura Pletsch-Borba, Francesca Porcellati, Ni Wang, Hirotaka Watada, Rosangela R Rea
{"title":"Once-weekly IcoSema versus once-daily insulin glargine U100 in type 2 diabetes management (COMBINE 4): an open-label, multicentre, treat-to-target, randomised, phase 3b trial.","authors":"Linong Ji, Malik Benamar, Viswanathan Mohan, Laura Pletsch-Borba, Francesca Porcellati, Ni Wang, Hirotaka Watada, Rosangela R Rea","doi":"10.1016/S2213-8587(26)00136-1","DOIUrl":"10.1016/S2213-8587(26)00136-1","url":null,"abstract":"<p><strong>Background: </strong>Stepwise treatment intensification is recommended for managing type 2 diabetes, including insulin initiation when non-insulin glucose-lowering medications are insufficient. Guidelines recommend combining a GLP-1 receptor agonist with basal insulin to improve glycaemic efficacy while reducing weight gain and hypoglycaemia risk. COMBINE 4 evaluated the efficacy and safety of IcoSema, a once-weekly combination therapy of basal insulin icodec and semaglutide (a GLP-1-receptor agonist) versus insulin glargine U100 (glargine U100) in people with type 2 diabetes on oral glucose-lowering medications.</p><p><strong>Methods: </strong>COMBINE 4 was a 40-week, randomised, open-label, treat-to-target, phase 3b trial conducted across 97 sites in nine countries. Adults (aged ≥18 years) with type 2 diabetes (HbA<sub>1c</sub> ≥8·0%) receiving oral glucose-lowering medications were randomly allocated in a 1:1 ratio without stratification to IcoSema or once-daily glargine U100. The titration target was 3·9-5·0 mmol/L (70-90 mg/dL). The primary endpoint was change in HbA<sub>1c</sub> and the secondary confirmatory endpoint was change in bodyweight, both from baseline to week 40, evaluated in all randomly allocated participants. Adverse events were recorded during weeks 0-45. This trial is registered with ClinicalTrials.gov (NCT06269107) and is complete.</p><p><strong>Findings: </strong>Of 653 individuals screened between Feb 15 and Aug 6, 2024, 151 did not meet screening criteria and 17 withdrew before initiating treatment; 243 were randomised to IcoSema and 242 to glargine U100. Of the 485 randomly allocated participants, 286 (59%) were male and 199 (41%) were female, and median age was 58 years (range 26-82). For HbA<sub>1c</sub>, from baseline (9·57% for IcoSema and 9·50% for glargine U100), mean change to week 40 was greater with IcoSema versus glargine U100 (-3·32 vs -2·44 percentage points; estimated treatment difference [ETD] -0·88 percentage points [95% CI -1·12 to -0·63]), confirming superiority of IcoSema (p<0·001). From baseline to week 40, mean bodyweight decreased with IcoSema and increased with glargine U100 (-0·79 vs 3·81 kg; ETD -4·61 kg [95% CI -5·46 to -3·75]), confirming superiority of IcoSema (p<0·001). Rate of combined clinically significant (blood glucose <3·0 mmol/L [<54 mg/dL], confirmed with a blood glucose meter) or severe hypoglycaemia (severe cognitive impairment requiring external assistance for recovery) was statistically significantly lower with IcoSema versus glargine U100 (0·29 vs 0·59 episodes per person-year of exposure; estimated rate ratio 0·56 [95% CI 0·32 to 0·97]; p=0·04). Gastrointestinal disorders were the most frequently reported adverse events with IcoSema.</p><p><strong>Interpretation: </strong>Once-weekly IcoSema demonstrated superior HbA<sub>1c</sub> reduction and bodyweight change, with lower rates of clinically significant or severe hypoglycaemia, versus glargine U100, suggesting that I","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":" ","pages":"831-840"},"PeriodicalIF":36.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761456","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}
Prof Jaakko Tuomilehto MD, Sudhirsen Kowlessur PhD, Prof Paul Zimmet MD, Jaysing Heecharan RN, Noorjehan Joonas PhD, Per Liv PhD, Prof Jonathan E Shaw MD, Prof Dianna J Magliano PhD, Prof Stefan Söderberg MD
{"title":"Trends in prevalence of type 2 diabetes and intermediate hyperglycaemia in Mauritius from 1987 to 2021 based on results from the oral glucose tolerance test: a repeated cross-sectional study","authors":"Prof Jaakko Tuomilehto MD, Sudhirsen Kowlessur PhD, Prof Paul Zimmet MD, Jaysing Heecharan RN, Noorjehan Joonas PhD, Per Liv PhD, Prof Jonathan E Shaw MD, Prof Dianna J Magliano PhD, Prof Stefan Söderberg MD","doi":"10.1016/s2213-8587(26)00127-0","DOIUrl":"https://doi.org/10.1016/s2213-8587(26)00127-0","url":null,"abstract":"Data on national trends in the prevalence of type 2 diabetes and intermediate hyperglycaemia using the oral glucose tolerance test (OGTT) are scarce. We aimed to identify trends in the prevalence of type 2 diabetes and intermediate hyperglycaemia in Mauritius, a country that has monitored prevalence over 34 years using OGTT.","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"14 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086992","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":"What Mauritius teaches us about diabetes surveillance","authors":"Shukri F Mohamed, Andre Pascal Kengne","doi":"10.1016/s2213-8587(26)00159-2","DOIUrl":"https://doi.org/10.1016/s2213-8587(26)00159-2","url":null,"abstract":"","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"60 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086990","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":"An important new data source for obesity trends in England.","authors":"Martin Gulliford","doi":"10.1016/S2213-8587(26)00130-0","DOIUrl":"10.1016/S2213-8587(26)00130-0","url":null,"abstract":"","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":" ","pages":"705-706"},"PeriodicalIF":36.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148320107","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}
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