OBJECTIVE:SURMOUNT-REAL UK will evaluate the effectiveness of tirzepatide when offered in addition to standard-of-care (SoC) in adults with Class I obesity (BMI ≥ 30 and ≤ 34.9 kg/m2) and without diabetes in a UK primary care setting. METHODS:A 5-year, phase 4, multicenter, open-label, pragmatic randomized clinical trial is enabled through access to participants' integrated electronic healthcare record data. The study will enroll approximately 3000 participants from Greater Manchester, UK, who are randomly assigned in a 1:1 ratio to receive either tirzepatide and SoC or SoC alone. RESULTS:The primary endpoint is the percent change in body weight from baseline to Month 24, with the time to onset of type 2 diabetes to Month 60 being the key secondary endpoint. Additional endpoints include the impact of tirzepatide versus SoC on obesity-related complications, health-related quality of life, healthcare resource utilization, productivity, employment, and sickness-related absences. CONCLUSIONS:SURMOUNT-REAL UK employs a novel study design to evaluate real-world health outcomes and potential long-term benefits for both participants and the healthcare system associated with the delivery of pharmacological obesity treatment at a population level. The study is intended to generate critical evidence to support informed decision-making in obesity management, clinical guideline development, and healthcare policy. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT07247084.

AIMS:Diabetes self management education (DSME) is recommended for type 2 diabetes, with completion widely accepted as ≥60% engagement. This review utilising PRISMA extension for scoping reviews maps the literature on the impact of full and partial completion of DSME on patient-reported outcomes (PROMs) versus a control. METHODS:Core search terms for type 2 diabetes were combined with DSME and PROMs (self care, diabetes distress and QOL) using the AND Boolean operator. Searches of CINAHL, MEDLINE and EMBASE 1 February, 2024, were checked September 2025. No restrictions were applied to study quality, location or sex. We examined quantitative studies comparing outcomes based on DSME completion [100%] vs. control [0%] vs. partial completion [1%-99%]. Studies employing ITT analyses or pre-post designs without controls were excluded to focus on outcomes by programme completion. RESULTS:Databases yielded 1307 records with an additional 12 through hand-searching key journals, reference lists and websites. Twenty-four records met inclusion criteria. No studies reported outcomes for partial DSME completion. Evidence suggests 100% DSME completion improves self management skills and QOL over 3-6 months, with greater gains in self care behaviours and mental health-related QOL. Medication adherence and physical health improved less consistently. CONCLUSIONS:Evidence of short-term improvements in self management skills and QOL was constrained by programme heterogeneity, methodological variability and predominantly high-income settings. Evidence supporting sustained benefits beyond 6-12 months is limited and impact on diabetes distress is uncertain. No studies reported the effectiveness of partial completion of DSME on PROMs, despite a widely accepted benchmark suggesting ≥60% engagement constitutes completion.

BACKGROUND:Weight recurrence and suboptimal response after metabolic and bariatric surgery (MBS) lack standardized definitions and management approaches, creating barriers to evidence-based treatment decisions and coordinated care across multiple specialties. OBJECTIVES:To establish international expert consensus on terminology, diagnostic approaches, and management strategies for suboptimal response and weight recurrence after MBS. SETTING:International Delphi study across multiple countries and health care systems. METHODS:A two-round modified Delphi study was conducted with 66 international experts across five specialties (MBS, obesity medicine, gastroenterology, endocrinology, dietetics and nutrition, and psychology). A 164-item questionnaire was developed, spanning seven dimensions: conservative management, diagnostic methods, endoscopic interventions, quantitative thresholds, risk factors, surgical interventions, and terminology. Consensus was defined a priori as ≥70% agreement. Inter-rater reliability was assessed using Gwet's AC1 coefficient. RESULTS:Response rates were 54.5% (Round 1) and 57.6% (Round 2). Consensus achievement improved significantly between rounds (26.2% to 40.9% of items). Experts reached unanimous agreement on core management principles including individualized patient care (100%) and the appropriateness of specialists prescribing antiobesity medications (100%). Strong consensus emerged on standardized terminology with "suboptimal" as the preferred term (89.5%) and %TWL as the optimal measurement approach (94.6). For quantitative thresholds, consensus was achieved on surgical nonresponse defined as <10% TWL at 12 months (73.0%), recurrent weight gain as >25% of lost weight from nadir (70.3%), and a 10% change in %EWL from nadir as normal physiologic response (83.8%). Conservative management items achieved the highest consensus rates (80.9%) while quantitative threshold items require additional research (28.1%). Inter-rater reliability improved across all domains, with conservative management achieving substantial agreement (AC1 = .70). CONCLUSION:Expert consensus was achieved on fundamental principles of postbariatric care, including preferred terminology, measurement metrics, and provider roles. These recommendations address important gaps in clinical practice standardization.

The primary analysis of the SELECT randomized clinical trial suggests that semaglutide reduced the rates of cardiovascular (CV) death, myocardial infarction, and stroke in patients with established CV disease (CVD) and overweight or obesity without diabetes. However, the effect of semaglutide on hospitalizations in this population remains unknown. To determine the impact of semaglutide on total hospital admissions and duration of hospital stay. The SELECT trial included patients aged 45 years or older with established CVD and a body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) of 27 or higher without diabetes at 804 clinical settings across North America, South America, Europe, Asia, Africa, and Australia. Patients were randomized from October 2018 to March 2021. This prespecified exploratory analysis was conducted from February 2024 to September 2025. Once-weekly subcutaneous semaglutide, 2.4 mg, or placebo. The total number of hospital admissions and days in hospital between the semaglutide and placebo groups. A total of 17 604 patients (median [IQR] age, 61.0 [55.0-68.0] years; 4872 female patients [27.7%]; median [IQR] BMI, 32.1 [29.7-35.7]) were followed up for a median (IQR) period of 41.8 (33.0-47.0) months. There were 11 287 hospital admissions. The number of total hospitalizations was lower in the semaglutide group vs placebo for any indication (18.3 vs 20.4 admissions per 100 patient-years; mean ratio [MR], 0.90; 95% CI, 0.85-0.95; P < .001) and for serious adverse events (15.2 vs 17.1 admissions per 100 patient-years; MR, 0.89; 95% CI, 0.84-0.94; P < .001). The number of days hospitalized for any indication per 100 patient-years was lower in the semaglutide group vs placebo (157.2 vs 176.2 days; rate ratio [RR], 0.89; 95% CI, 0.82-0.98; P = .01), as well as hospitalizations for serious adverse events (137.6 vs 153.9 days; RR, 0.89; 95% CI, 0.81-0.98; P = .02). No heterogeneity was observed for the reduction of hospital admissions with semaglutide in selected subgroups, including BMI, age, and sex. In this prespecified exploratory analysis of the SELECT randomized clinical trial, the trial cohort had a high rate of hospital admissions. Treatment with once-weekly semaglutide was associated with significant reductions in hospital admissions and overall time spent in hospital, extending its benefits beyond CV risk reduction. ClinicalTrials.gov Identifier: NCT03574597

Introduction and Objective: Mortality is increased in type 2 diabetes, but a 2025 scoping review reported a 45% mortality risk reduction (pooled RR 0.55, 95% CI 0.47-0.63, p < 0.0001) after DSME(1). We examined DSME impact on cause specific mortality rates in type 2 diabetes in England. Methods: In a retrospective epidemiological analysis, primary care records of 364,703 adults with type 2 diabetes were linked to UK Office for National Statistics mortality data(2) in patients matched at baseline for age, sex, age at diagnosis and diabetes duration. We used Poisson and negative binomial regression to estimate all-cause and cause-specific mortality rates in those that had ever (n=75,343) or never (n=289,360) had DSME, adjusting for covariates. Results: In patients, mean age 70 years, diabetes duration 6 years and HbA1c 7.9%, there were 11,230 deaths in those who had ever and 73,010 in those who had never attended DSME. All-cause mortality was lower in DSME attendees (26.99 vs. 44.85 deaths per 1,000 person-years, rate ratio [RR] 0.60), incidence rate ratio 37% (0.63, 0.61-0.64, p<0.001), including renal disease (0.42), diabetes (0.47), sepsis (0.45), dementia (0.49), liver disease (0.49), respiratory disease (0.51), and stroke (0.51). Conclusion: DSME attendance was associated with lower all-cause and cause-specific mortality in adults with type 2 diabetes, underscoring the importance of DSME, although causality cannot be inferred. Disclosure G.A. Lewis: None. D. Hughes: None. G. Irving: None. J. Wilding: Advisory Panel; Ended; Alnylam Pharmaceuticals, Inc. Advisory Panel; Current; Amgen Inc., AstraZeneca, Kailera, Eli Lilly and Company. Speaker's Bureau; Current; Medscape. Advisory Panel; Ended; Menarini Group. Advisory Panel; Current; Novo Nordisk A/S. Advisory Panel; Ended; Pfizer Inc., Saniona. Speaker's Bureau; Current; Boehringer Ingelheim International GmbH. Advisory Panel; Ended; Shionogi & Co., Ltd. K.J. Hardy: None.

Introduction and Objective: Type 2 diabetes increases all-cause hospitalization. A 2025 scoping review reported a non-significant 9% reduction in hospitalization with DSME (pooled RR 0.91, 95% CI 0.76-1.10, p<0.34)(1). We examined DSME impact on hospital admission rates in type 2 diabetes in England. Methods: In a retrospective epidemiological analysis, primary care records of 364,703 adults with type 2 diabetes were linked to UK Hospital Episode Statistics(2) in patients matched at baseline for age, sex, age at diagnosis and diabetes duration. We used Poisson and negative binomial regression to estimate all cause and cause specific admission rates in those who had ever (n=75,343) or never (n=289,360) had DSME, adjusting for covariates. Results: In patients, mean age 70 years, diabetes duration 6 years, and HbA1c of 7.9%, there were 2,087,097 admissions in ever and 9,885,238 in never had DSME. All-cause admissions were lower in DSME (5015.98 vs. 6071.99 admissions per 1,000 person-years, RR 0.83, adjusted IRR 0.88 95% CI 0.87-0.89, p<0.001). After covariate adjustment, DSME was associated with fewer admissions for diabetes, kidney infections, liver disease, renal disease, respiratory disease, other cancers, and stroke. Conclusion: DSME was associated with lower all-cause and some cause-specific hospitalizations in adults with type 2 diabetes, underscoring the importance of DSME; causality cannot be inferred. Disclosure G.A. Lewis: None. D. Hughes: None. G. Irving: None. J. Wilding: Advisory Panel; Ended; Alnylam Pharmaceuticals, Inc. Advisory Panel; Current; Amgen Inc., AstraZeneca, Kailera, Eli Lilly and Company. Speaker's Bureau; Current; Medscape. Advisory Panel; Ended; Menarini Group. Advisory Panel; Current; Novo Nordisk A/S. Advisory Panel; Ended; Pfizer Inc., Saniona. Speaker's Bureau; Current; Boehringer Ingelheim International GmbH. Advisory Panel; Ended; Shionogi & Co., Ltd. K.J. Hardy: None.

Introduction Approximately 15 million people in the UK live with obesity and at least 5 million of these are people with severe obesity (PWSO). Severe obesity significantly compromises health, well-being and quality of life and reduces life expectancy. These adverse outcomes are prevented or ameliorated by weight loss, for which sustained behavioural change is the cornerstone of treatment. Several studies suggest the potential of group-based intervention in Specialist Weight Management Services (SWMS), but PWSO remain underrepresented in research, and evidence on optimal design and outcomes is limited. The success of the PROGROUP feasibility randomised controlled trial (RCT) (ISRCTN22088800) informed the development of this study and additional adjustments have been made in response to the rollout of obesity management medication in the National Health Service (NHS). This study aims to assess the effectiveness and cost-effectiveness of PROGROUP in SWMS and primary care.Methods and analysis The RCT will be conducted in SWMS, alongside an implementation study in primary care. The RCT will recruit cohorts of 30 participants to be randomised 1:1 within-cohort to PROGROUP (intervention) or usual care (control). The implementation arm will recruit cohorts of 15 to PROGROUP. The primary objectives for the study are to undertake a process evaluation and economic evaluation of PROGROUP in the RCT and to assess its implementation in primary care. Baseline data and outcome differences at 6 months will be analysed. These will include weight, other clinical measures and patient-reported outcomes, including social and life-satisfaction measures.Ethics and dissemination This study is approved by an NHS Research Ethics Committee (REC reference: 23/WS/0101). Results will be reported in a manuscript that will be submitted to a peer-reviewed medical journal as open access. A lay summary of the findings will be published online, and participants and sites will be signposted to this.Trial registration number ISRCTN13721429.

Tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist approved in the US for treating type 2 diabetes (T2D) and obesity, has demonstrated significant improvements in glycated hemoglobin A1c (HbA1c) and clinically meaningful weight loss in the SURPASS-1 to -5 clinical trials. This post hoc analysis examined the safety and efficacy results for tirzepatide in older participants with T2D who do not have obesity. A post hoc analysis was conducted on a subgroup of participants aged ≥ 65 years with a body mass index (BMI) < 30 kg/m2 amongst the pooled SURPASS-1 through -5 clinical trial populations. Primary efficacy endpoints and safety were assessed for both this subgroup and overall pooled populations. Participants aged ≥ 65 years with BMI < 30 kg/m2 treated with tirzepatide experienced clinically meaningful HbA1c reduction (− 1.97 to − 2.10

INTRODUCTION:Type 2 diabetes is associated with excess hospital admissions and increased mortality. Structured diabetes self-management education (DSME) is recommended internationally and is associated with improved self-management skills, well-being and minor improvements in glycated haemoglobin (HBA1c), but does it reduce hospital admissions or prevent premature mortality? Our aim is to examine the relationship between DSME attendance, hospitalisations, mortality and 3-point major adverse cardiovascular events (MACE) in people with type 2 diabetes to inform future healthcare policy and diabetes care. METHODS AND ANALYSIS:This protocol details a 10-year retrospective open cohort study of patients aged over 18 years old who have a clinical diagnosis of type 2 diabetes and were registered to an English GP practice from 29 March 2011 to 29 March 2021 and have attended DSME. Patients in the 'ever' cohort will be matched at baseline for age, sex, age at diagnosis and diabetes duration, to those who have 'never' attended DSME. Data will be identified via the UK Clinical Practice Research Datalink and linked to Hospital Episode Statistics Admitted Patient Care data, Office for National Statistics death registrations and patient Index of Multiple Deprivation deciles. Patients will be followed-up through serial cross-sections. Multiple imputation will be considered to manage covariates where data are >12-months from baseline or are not expected to be missing at random. Cox proportional hazard regression and time to event modelling adjusted a priori for cofounding during multivariate analysis will be used. ETHICS AND DISSEMINATION:This study was approved by CPRD (24_003744). Study findings will be disseminated through peer-reviewed publications and international conferences.

OBJECTIVE:The objective of this study was to assess safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo, beyond reduction in major adverse cardiovascular events, in patients with established cardiovascular disease and overweight or obesity. METHODS:Safety data focused on serious adverse events (SAEs), all adverse events (AEs) leading to permanent treatment discontinuation irrespective of seriousness, and prespecified AEs of special interest irrespective of seriousness. Tests of treatment differences were determined by two-sided p values. RESULTS:The proportion of patients with SAEs was lower with semaglutide versus placebo (33.4% vs. 36.4%; p < 0.001), primarily driven by cardiac disorders (11.5% vs. 13.5%; p < 0.001). The proportion of patients with AEs leading to discontinuation was higher with semaglutide versus placebo (16.6% vs. 8.2%; p < 0.001), a difference driven by gastrointestinal disorders (10.0% vs. 2.0%); however, proportions due to SAEs leading to discontinuation were similar (3.6% vs. 4.1%). Suicide/self-injury SAEs were low and balanced between groups (0.11% in both groups). Gallbladder-related disorders were more frequent with semaglutide versus placebo (2.8% vs. 2.3%; p = 0.04), mainly driven by cholelithiasis (1.4% vs. 1.1%), whereas proportions of cholecystitis were similar between groups (0.6% vs. 0.6%). CONCLUSIONS:The long-term safety profile observed in the Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity (SELECT) study is consistent with previously reported semaglutide studies. No new safety concerns were identified for once-weekly semaglutide 2.4 mg.

Background/Objectives: The STRIVE study was a multicentre, open-label, real-world clinical trial evaluating the effectiveness of a targeted prescribing pathway for liraglutide 3.0 mg as an adjunct to standard care versus standard care alone in people with obesity attending Specialist Weight Management Services (SWMS) in the UK and Ireland. This post hoc analysis focuses on the standard care arm to explore differences in outcomes between sites, particularly the potential impact of offering meal replacements as part of usual care. Methods: Participants included individuals with a BMI ≥ 35 kg/m² and at least one obesity-related complication who received standard care at five SWMS sites. All sites provided specialist nutrition and exercise counselling; however, only the Dublin site (n = 40) included meal replacements as part of routine care. Baseline characteristics and weight change data were compared between the Dublin and UK cohorts (n = 92) at 52 and 104 weeks. Statistical comparisons were made using appropriate parametric and non-parametric tests. Results: At baseline, the Dublin cohort was significantly older (p < 0.01), had a higher prevalence of hypertension (p < 0.05), and a lower reported incidence of depression/anxiety (p < 0.05) than the UK cohort. At week 52, the Dublin group achieved greater mean weight loss (-6.1%, SD ± 5.7%) compared to the UK cohort (-1.3%, SD ± 6.7%, n = 27, p < 0.01). By week 104, Dublin participants maintained a mean weight loss of -4.4% (SD ± 5.7%) while UK participants had a mean weight gain of 0.37% (SD ± 7.6%) (p < 0.05). Conclusions: The integration of meal replacements as part of usual care may have contributed to the greater and sustained weight loss observed in the Dublin cohort compared to other SWMS in the UK.

Obesity medications are recommended in England with legislation necessitating their availability. However, given the number of people who meet clinically approved eligibility criteria, funding these medications and associated support services may limit efficacy at a population health level. This study aimed to assess the commissioning and availability of services and obesity medications across England. Three sets of freedom of information requests were sent to the 42 ICBs in England by Sky News Ltd, The BMJ and the study investigators of this work with questions focused on commissioning of services and medication eligibility and prescription across England. The three data sets were combined to provide a narrative description to inform further development in obesity care. The availability of services across England was partial, and when services did exist, medication access was limited by funding and more restrictive eligibility criteria beyond those approved by the National Institute of Health and Care Excellence. Subsequently, very few patients receive NHS prescriptions even in areas where funding medications are reportedly available. The capacity of services to offer comprehensive care for patients to receive obesity medications is insufficient to meet current demand. Despite legislation for the delivery of obesity medications, these treatment options are not widely available on the NHS. There is insufficient service capacity to provide comprehensive care for eligible patients seeking obesity medications as a treatment option.

BACKGROUND:Semaglutide at a dose of 2.4 mg has established weight-loss and cardiovascular benefits, and cagrilintide at a dose of 2.4 mg has shown promising results in early-phase trials; the efficacy of the combination (known as CagriSema) on weight loss in persons with either overweight and coexisting conditions or obesity is unknown. METHODS:In a phase 3a, 68-week, multicenter, double-blind, placebo-controlled and active-controlled trial, we enrolled adults without diabetes who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or higher or a BMI of 27 or higher with at least one obesity-related complication. Participants were randomly assigned in a ratio of 21:3:3:7 to receive the combination of semaglutide at a dose of 2.4 mg and cagrilintide at a dose of 2.4 mg, semaglutide alone at a dose of 2.4 mg, cagrilintide alone at a dose of 2.4 mg, or placebo, plus lifestyle interventions for all groups. The coprimary end points were the relative change in body weight and a reduction of 5% or more in body weight from baseline to week 68 with cagrilintide-semaglutide as compared with placebo. Body-weight reductions of 20% or more, 25% or more, and 30% or more were assessed as confirmatory secondary end points. Effect estimates were assessed with the treatment-policy estimand (consistent with the intention-to-treat principle). Safety was assessed. RESULTS:A total of 3417 participants underwent randomization, with 2108 assigned to receive cagrilintide-semaglutide, 302 to receive semaglutide, 302 to receive cagrilintide, and 705 to receive placebo. The estimated mean percent change in body weight from baseline to week 68 was -20.4% with cagrilintide-semaglutide as compared with -3.0% with placebo (estimated difference, -17.3 percentage points; 95% confidence interval, -18.1 to -16.6; P<0.001). Participants receiving cagrilintide-semaglutide were more likely than those receiving placebo to reach weight-loss targets of 5% or more, 20% or more, 25% or more, and 30% or more (P<0.001 for all comparisons). Gastrointestinal adverse events (affecting 79.6% in the cagrilintide-semaglutide group and 39.9% in the placebo group), including nausea, vomiting, diarrhea, constipation, or abdominal pain, were mainly transient and mild-to-moderate in severity. CONCLUSIONS:Cagrilintide-semaglutide provided significant and clinically relevant body-weight reductions in adults with overweight or obesity, as compared with placebo. (Funded by Novo Nordisk; REDEFINE 1 ClinicalTrials.gov number, NCT05567796.).

BACKGROUND:Galectin-3 (Gal-3) is a circulating biomarker of fibrosis, with higher levels being associated with an increased risk of progression of heart failure and kidney disease. Patients with type 2 diabetes mellitus (T2DM) are at increased risk of both. METHODS:DECLARE-TIMI 58 was a randomized, placebo-controlled trial of dapagliflozin in patients with T2DM with or at high risk for atherosclerotic cardiovascular disease and creatinine clearance ≥60 mL/min. In a nested biomarker substudy, Gal-3 was measured at baseline and in adjusted analyses associated with the prespecified kidney-specific composite endpoint [Kidney-EP; sustained ≥40% decrease in estimated glomerular filtration rate (eGFR) to <60 mL/min, new end-stage kidney disease or adjudicated kidney-related death]. RESULTS:Among 14 530 pts, median Gal-3 was 14.9 ng/mL [interquartile range (IQR), 11.9, 18.4]. Gal-3 was weakly associated with urine albumin creatinine ratio (r = 0.098, P < 0.0001) and eGFR (r = -0.27, P < 0.001) at baseline and independently associated with the Kidney-EP:adj hazard ratio (HR) 1.15 [95% confidence interval (CI) 1.03, 1.28] per 1-SD log (Gal-3), P = 0.013. Dapagliflozin significantly reduced the relative risk of the Kidney-EP across quartiles of baseline Gal-3 [overall HR 0.45 (95% CI 0.23, 0.85), P < 0.0001; P interaction = 0.87]. A greater risk difference was observed with dapagliflozin in patients with higher Gal-3, in whom a higher absolute risk at baseline was observed [absolute risk reduction (ARR) Q4 1.9 (95% CI 0.6, 3.2) vs. Q1 0.6% (-0.1, 1.3), ARR P trend 0.048]. CONCLUSIONS:Plasma Gal-3 is independently associated with the progression of kidney dysfunction in patients with T2DM and normal kidney function. There was a gradient of greater absolute benefit for reducing kidney disease progression in patients treated with dapagliflozin and with higher Gal-3 concentrations at baseline, in whom a higher absolute risk was observed. REGISTRATION:clinicaltrials.gov (NCT01730534).

BACKGROUND Obesity is a chronic disease and causal precursor to myriad other conditions, including type 2 diabetes. In an earlier analysis of the SURMOUNT-1 trial, tirzepatide was shown to provide substantial and sustained reductions in body weight in persons with obesity over a 72-week period. Here, we report the 3-year safety outcomes with tirzepatide and its efficacy in reducing weight and delaying progression to type 2 diabetes in persons with both obesity and prediabetes. METHODS We performed a phase 3, double-blind, randomized, controlled trial in which 2539 participants with obesity, of whom 1032 also had prediabetes, were assigned in a 1:1:1:1 ratio to receive tirzepatide at a once-weekly dose of 5 mg, 10 mg, or 15 mg or placebo. The current analysis involved the participants with both obesity and prediabetes, who received their assigned dose of tirzepatide or placebo for a total of 176 weeks, followed by a 17-week off-treatment period. The three key secondary end points, which were controlled for type I error, were the percent change in body weight from baseline to week 176 and onset of type 2 diabetes during the 176-week and 193-week periods. RESULTS At 176 weeks, the mean percent change in body weight among the participants who received tirzepatide was -12.3% with the 5-mg dose, -18.7% with the 10-mg dose, and -19.7% with the 15-mg dose, as compared with -1.3% among those who received placebo (P<0.001 for all comparisons with placebo). Fewer participants received a diagnosis of type 2 diabetes in the tirzepatide groups than in the placebo group (1.3% vs. 13.3%; hazard ratio, 0.07; 95% confidence interval [CI], 0.0 to 0.1; P<0.001). After 17 weeks off treatment or placebo, 2.4% of the participants who received tirzepatide and 13.7% of those who received placebo had type 2 diabetes (hazard ratio, 0.12; 95% CI, 0.1 to 0.2; P<0.001). Other than coronavirus disease 2019, the most common adverse events were gastrointestinal, most of which were mild to moderate in severity and occurred primarily during the dose-escalation period in the first 20 weeks of the trial. No new safety signals were identified. CONCLUSIONS Three years of treatment with tirzepatide in persons with obesity and prediabetes resulted in substantial and sustained weight reduction and a markedly lower risk of progression to type 2 diabetes than that with placebo.

Type 2 diabetes is associated with increased all‐cause hospital admissions and premature mortality. Diabetes self‐management education ( DSME ) is internationally recommended but its impact on reducing hospital admissions and premature mortality is unclear. This scoping review followed the PRISMA extension for scoping reviews and explores the relationship between DSME , hospital admissions and mortality in adults with type 2 diabetes. Core search terms for type 2 diabetes were combined with terms for DSME , hospital admission, and mortality. Searches were conducted on 10 January 2024, and checked in September 2025, across three electronic databases: CINAHL , MEDLINE , and EMBASE . No restrictions were applied regarding study design, quality, location, or sex. The search yielded 294 records from databases and 66 from manual searches; 42 met inclusion criteria. Evidence regarding hospitalisation was inconsistent, with heterogenous outcome definitions and frequent reporting of admissions as a reason for attrition. Meta‐analysis showed a non‐significant 9% reduction in admission risk among DSME groups. By contrast, meta‐regression found that whether mortality was reported as a primary outcome significantly moderated the treatment effect ( p = 0.0002), fully accounting for between‐study heterogeneity (τ 2 = 0; I 2 = 0%; R 2 = 100%). A final pooled analysis, restricted to studies with mortality as a primary outcome, demonstrated a ~45% reduction in mortality risk ( RR 0.55, 95% CI 0.47–0.63, p < 0.0001). DSME may offer a survival benefit for adults with type 2 diabetes, but current evidence does not support an association with reduced hospitalisation. Standardisation of DSME content and outcome reporting is essential to improve comparability.

Lymphedema is an important, and often underdiagnosed complication of obesity and is likely due to acquired defects in the lymphatic vasculature. Study of diet-induced obesity animal models have indicated defective lymphatic vasculatures might extend to other anatomical sites, especially visceral depots. Excess mechanical pressure, metabolites, pro-inflammatory cytokines, and adipokines released during adipose tissue expansion can predispose lymphocytes to overactivation and apoptosis; compromising collecting lymphatic vessels; and triggering lymph node hypoplasia, fibrosis, and apoptosis. Consequently, the defective lymphatic vasculature may disrupt local and systemic immune-metabolic homeostasis, contributing to various adverse outcomes including inflammation and immune dysfunction, abnormal transport dynamics of lipids, vitamin D, and possibly incretin in obesity. Weight reduction is the definitive management to restore lymphatic function and should be instituted before permanent vasculature impairment develops. Besides lymphatic regeneration, future research aimed at elucidating the pathophysiological mechanisms between adipose tissue and lymphatic vasculature should be considered to help the development of potential adjunctive therapies that might repair the lymphatic vasculature, improve immune-metabolic outcomes, and even combat obesity.