Novo Nordisk (Switzerland)

This study aimed to investigate glycaemic control and safety in Chinese adults with type2 diabetes (T2D) receiving fixed-ratio combination of insulin degludec and liraglutide (IDegLira) in real-world clinical practice. The Tianjin Health and Medical Big Data Super Platform was utilised to assess clinical characteristics, glycaemic control, and safety of Chinese adults with T2D receiving IDegLira between March 5, 2022 and June 30, 2024. The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to day180. Secondary endpoints included change in HbA1c by baseline characteristics; change in fasting plasma glucose (FPG), postprandial glucose (PPG), and daily insulin dose; and treatment persistence. Exploratory endpoints included hypoglycaemic events and gastrointestinal adverse events (GI AEs). Eligible participants were included in the full analysis set and safety analysis set (both n = 12,103), and participants receiving IDegLira for 180days were included in the effectiveness analysis set (n = 3062). The mean (SD) change in HbA1c, FPG, PPG, and insulin dose after 180days from baseline was - 1.08% (1.87, p < 0.001), - 2.34mmol/L (3.61, p < 0.001), - 2.10mmol/L (4.86, p < 0.001), and - 4.95U/day (21.93, p < 0.001), respectively. Subgroup analyses of HbA1c change demonstrated that IDegLira decreased HbA1c significantly, irrespective of prior treatment, age, most baseline HbA1c, daily insulin dose, and fasting C-peptide quartiles. Median treatment persistence duration was 141.67days (95%CI 135.67-146.67). Low percentages of patients reported hypoglycaemia (0.7%) or GI AEs (11.1%). IDegLira statistically improved glycaemic control by reducing HbA1c, FPG, and PPG levels in the Chinese population with T2D, with a favourable safety profile.

ABSTRACTAimsObesity‐related complications (ORCs) are associated with substantial health and economic burdens. Although treatment targets are routinely used for other chronic conditions, none currently exist in obesity management. We aimed to identify an adiposity measure that indicates a reduced risk of four ORCs.Materials and MethodsThis population‐based cohort study of patients aged 18–60 years used data from the UK Clinical Practice Research Datalink Aurum. Associations between absolute 10‐year ORC risk and baseline body mass index (BMI), waist–height ratio (WHtR), and changes in adiposity measures after weight loss were calculated. Absolute values and changes in adiposity measures were evaluated as a proxy for achieving an absolute 10‐year ORC risk similar to that of people without obesity, and optimal cut‐offs were identified based on the balance between true positive and true negative rates for achieving the treatment goal.ResultsAbsolute values of BMI and WHtR post‐weight change were more strongly associated with 10‐year ORC risk than relative changes; WHtR was the best proxy for a low absolute risk for type 2 diabetes, hypertension, and atherosclerotic cardiovascular disease, and BMI for hip/knee osteoarthritis. Based on the balance between true negative and true positive rates of multiple cut‐offs, a BMI ≤ 27 kg/m2 and WHtR ≤ 0.53 are proposed as potential treatment targets for obesity.ConclusionsThese findings suggest that treatment goals for obesity management may be considered on post–weight‐change absolute adiposity measures, rather than relative changes. Both weight and WHtR may be considered when defining treatment targets for ORC risk reduction.

IntroductionIcoSema is under development as a once-weekly injectable combination therapy of icodec (basal insulin) and semaglutide (glucagon-like peptide 1 receptor agonist). This study assessed the pharmacokinetic characteristics of icodec and semaglutide following IcoSema administration vs. administration of icodec and semaglutide alone in Chinese individuals with type 2 diabetes (T2D).MethodsIn a randomized, double-blind, three-period crossover study, 20 Chinese individuals with T2D (18–64 years, body mass index 18.5–34.9 kg/m2, glycated hemoglobin ≤ 9.0%) were given single subcutaneous administrations of IcoSema, icodec, or semaglutide separated by 6–9 weeks. Blood was drawn for pharmacokinetic measurement until 840 h post dose.ResultsCombining icodec with semaglutide had no impact on icodec pharmacokinetics. The ratio and 90% confidence interval of IcoSema/icodec was 1.04 [0.99;1.08] for area under the curve from zero to last quantifiable observation (AUC0–t) and 1.02 [0.96;1.09] for maximum concentration (Cmax), i.e., within the bioequivalence acceptance interval of 0.80–1.25. Likewise, combining semaglutide with icodec had no impact on semaglutide AUC0–t (IcoSema/semaglutide 0.99 [0.94;1.05]). However, semaglutide Cmax was higher for IcoSema vs. semaglutide alone (1.42 [1.31;1.53]) and occurred earlier for IcoSema (12 vs. 66 h). All three treatments were safe with no differences in frequency, severity or outcome of adverse events, or relationship to study product.ConclusionIn Chinese individuals with T2D, icodec pharmacokinetics and semaglutide total exposure are unaffected when combining icodec and semaglutide in IcoSema. However, maximum semaglutide concentration is higher and occurs earlier with IcoSema. This information may help to ensure suitable dose recommendations for IcoSema.Trial RegistrationClinicalTrials.gov identifier, NCT05435677.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-025-01803-x.

AimsThe link between health and economic prosperity is well established, yet quantifying the value of illness prevention remains challenging due to lack of comprehensive metrics. Obesity exemplifies this issue, having widespread societal and health care impacts but limited prevention funding. Existing metrics often fail to capture broader effects of prevention of obesity. This study aimed to identify key components for a holistic metric to assess obesity and cardiometabolic health progression, better articulating value of prevention.Materials and MethodsWe conducted a targeted literature review to identify existing individual and composite metrics for prevention in adults, agnostic of disease or risk factor. We categorized endpoints into: (i) holistic composite measures; (ii) user‐centred composite measures; (iii) health outcome composite measures; (iv) single clinical endpoints. Metrics were evaluated against eight criteria including holistic outcome, cardiometabolic relevance, data feasibility, geographical generalizability, established outcome, economic modelling methodology, stakeholder relevance and preventive value; alongside semi‐structured review from six clinical, health economics and policy experts.ResultsCardiometabolic endpoints numbering 74 were identified: 7 holistic composites, 16 user‐centred composites, 31 health‐based composites and 20 single clinical endpoints. Five endpoints were shortlisted according to assessment criteria and expert input: waist‐to‐height ratio, low‐density lipoprotein cholesterol, systolic and diastolic blood pressure, blood glucose and the 12‐Item Short Form Health Survey (SF‐12). These endpoints collectively reflected physiological cardiometabolic risk factors with an adverse association with obesity, while SF‐12 provided health‐related quality‐of‐life measurement.ConclusionsWe developed a novel framework that shortlisted five key cardiometabolic outcome measures for assessing obesity primary prevention benefits, with potential applications in health economic modelling and public health.

Patients with sickle cell disease (SCD) experience painful vaso-occlusive episodes that increase with age; a subset develops chronic pain (CP). CP is usually managed with acute pain management guidelines despite evidence of ineffectiveness. Buprenorphine (BUP), a partial opioid agonist, is a potent analgesic with less euphoric effect and a respiratory "ceiling effect." BUP therefore provides an alternative "harm reduction" approach for CP management in pediatric SCD patients. This single urban center retrospective study assessed the feasibility of inpatient transition to BUP-containing analgesics in adolescents with SCD and CP. Patients aged 12-20years who transitioned from full opioid agonists (FOA) to BUP between December 2020 and September 2022 were included. Acute care utilization, hospital length of stay, and FOA use in both inpatient and outpatient settings were compared pre- and post-BUP induction for up to a year. Fourteen adolescents with SCD underwent inpatient BUP induction and maintenance therapy. Inpatient transition using a micro-induction approach was feasible and well tolerated in this population. There were low rates of adverse events, such as opioid withdrawal signs. Maintenance on BUP products was sustainable over the 1-year post-induction period. Three patients (21%) discontinued BUP during maintenance therapy. There was a significant reduction (p<0.05) in acute care utilization, length of stay, and FOA use (both inpatient and outpatient). Inpatient micro-induction to BUP from FOA in adolescent SCD patients with CP is feasible with minimal signs of opioid withdrawal. This study suggests decreased acute care utilization with BUP.

Background: Treatment of atrial fibrillation (AF) in horses is challenged by high recurrence rates, potentially driven by underlying myocardial changes or remodelling caused by AF itself. Understanding the molecular mechanisms behind these changes is

Plain Language SummaryIdiopathic short stature (ISS) is the name for when a child is much shorter in height than expected for their age. Children with ISS may grow taller when they receive growth hormone treatment (GHT), but not always. We looked at data from children with ISS who had received GHT to identify factors that could predict how much a child grew on treatment. We used information from two reports where children with ISS were treated with GHT. Our study included 207 boys and girls with ISS who were aged between 3 and 11 years when they started GHT. None of the children had started puberty. We looked at how many children grew after 1 year on GHT compared with their expected height for their age and sex, termed response to GHT. Based on their response, children were defined as having a “good response,” “middle response,” or “poor response”. Then, we checked if any other factors affected how well children responded to GHT. Children with ISS who grew the most (had a good response to GHT) were younger at the start of treatment and further away from their expected height than children who grew the least (had a poor response to GHT). We also found that children who got a higher dose of GHT grew more than those who got a lower dose. These results may help doctors predict how much a child might grow on GHT, which could help doctors, patients and caregivers to make decisions about treatment.