Introduction and Objective: Type 1 Diabetes (T1D) is caused by autoimmune loss of pancreatic β-cells, and current insulin therapy does not address the underlying immune process. Antigen-specific tolerance approaches remain an unmet need. CARC-101C is a first-in-human engineered red blood cell (eRBC) therapy presenting an insulin autoantigen using the non-genetic Readilase™ platform. This study evaluated its safety and biological activity in adults with autoimmune T1D. Methods: Adults with T1D who were insulin autoantibody (IAA)-positive at the onset of disease and still retained measurable C-peptide were enrolled (n=3). CARC-101C was produced by conjugating an insulin autoantigen peptide onto RBC membranes. All participants received a single IV infusion of 3×1010 cells. The primary endpoint was safety within 3 weeks. Secondary measures included C-peptide, insulin use, CGM metrics, and immune biomarkers over 76 weeks. Results: CARC-101C was well tolerated. No serious adverse events occurred, and all events were Grade 1 and transient, with no infusion reactions, immune activation, cytokine elevations, hemolysis, or alloimmunization. One participant (36-week follow-up) showed a sustained 2-3-fold rise in C-peptide through 36 weeks, reduced insulin needs, and a 28-week insulin-free period with preserved CGM control. The other two participants (36-week and 12-week follow-up) showed β-cell function within expected clinical variability, and insulin use remained stable. IAA levels in all participants were stable or decreased. Conclusion: A single low-dose infusion of CARC-101C demonstrated a favorable safety profile with no immune activation in adults with T1D. For some patients with residual β-cell activity, CARC-101 may help slow the decline of islet function. These findings support continued clinical evaluation of eRBC-based autoantigen delivery as a well-tolerated and clinically practical strategy for antigen-specific immune tolerance in T1D. Disclosure J. Lu: None. D. Zhu: None.

BACKGROUND:Finerenone is a novel nonsteroidal mineralocorticoid receptor antagonist. However, robust evidence about its efficacy and safety in primary aldosteronism is scarce. METHODS:In this prospective, multicenter, single-arm, and exploratory trial, we enrolled adults (aged ≤75 years) with primary aldosteronism, an office blood pressure (BP) ranging from 140 to 180/90 to 120 mm Hg, and an estimated glomerular filtration rate ≥60 mL/min per 1.73 m². Eligible patients received finerenone (20-40 mg/d) treatment for 12 weeks. The primary outcome was the change in daytime systolic BP at 12 weeks. RESULTS:Fifty-seven patients were ultimately treated. Per-protocol analysis revealed that finerenone treatment significantly reduced mean daytime systolic BP (-6.69±1.60 mm Hg; P<0.001) and diastolic BP (-4.55±1.06 mm Hg; P<0.001) according to ambulatory monitoring. Mean office BP decreased even more substantially (systolic BP, -15.58±1.69 mm Hg; diastolic BP, -8.61±1.02 mm Hg; both P<0.001). The mean increase in serum potassium concentration was 0.39±0.05 mmol/L, and 94.5% of patients exhibited a normal concentration after 12 weeks of treatment (versus baseline 61.8%; P<0.001). Plasma renin activity increased, and 32.7% of patients exhibited a plasma renin activity concentration ≥1 ng/mL per h. According to the Primary Aldosteronism Medical Treatment Outcome criteria, 29.1% and 20.0% of patients achieved complete biochemical and clinical responses, respectively. Treatment was well tolerated. CONCLUSIONS:This study demonstrated the efficacy and safety of finerenone in the treatment of primary aldosteronism, supporting its use as a potential alternative therapy for the condition. Nevertheless, further prospective and head-to-head randomized controlled trials are essential to establish finerenone as a viable substitute for spironolactone. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06381323.

Introduction:Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, reduced the risk of heart and kidney outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in FIDELITY, a prespecified pooled analysis of the FIDELIO-DKD and FIGARO-DKD trials. This subanalysis explored the efficacy and safety of finerenone vs. placebo in Chinese patients. Methods:Patients with CKD (urine albumin-to-creatinine ratio 30-5,000 mg/g, estimated glomerular filtration rate [eGFR] ≥25 mL/min/1.73 m2) and T2D, on optimized renin-angiotensin system inhibitors, were randomized 1:1 to finerenone or placebo. Key outcomes included a kidney composite (kidney failure, sustained ≥57% eGFR decrease from baseline over ≥4 weeks, or kidney-related death) and a cardiovascular (CV) composite (CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure). An additional kidney composite outcome was kidney failure, sustained ≥40% eGFR decrease from baseline over ≥4 weeks, or kidney-related death. Treatment-emergent adverse events were also assessed. Results:In this Chinese patient subanalysis (n = 697), finerenone reduced the risk of the ≥57% and ≥40% kidney composite outcomes (hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.38-0.86; p = 0.0066 and HR: 0.54; 95% CI: 0.40-0.74; p < 0.0001, respectively) and CV composite outcome risk vs. placebo (HR: 0.82; 95% CI: 0.52-1.29; p = 0.3866). Safety outcomes were similar between treatment arms. Hyperkalemia leading to treatment discontinuation was low for finerenone (2.6%) and placebo (0.9%). Conclusion:Finerenone demonstrated kidney benefits, favorable trends on CV outcome, and a manageable safety profile in the FIDELITY Chinese subpopulation.

To determine the optimal timing for initiating liraglutide in patients with persistent obesity (BMI ≥ 28 kg/m² in China) six months after metabolic and bariatric surgery, a key gap in postoperative weight management. In this prospective study, 100 patients were allocated to receive liraglutide (3.0 mg/day) starting at 6 (LG-6), 9 (LG-9), or 12 (LG-12) months post-surgery, or standard care without liraglutide (n = 25 each). The primary endpoint was percent total weight loss (

Ecnoglutide is a cAMP-biased GLP-1 analogue developed for the treatment of type 2 diabetes mellitus (T2DM) and obesity. We conducted a randomised, double-blind, placebo-controlled, phase 3 trial to evaluate the efficacy and safety of ecnoglutide in adults with T2DM inadequately controlled with diet and exercise alone or with a single oral hypoglycaemic agent. The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline at week 24. Between 29 December 2022 and 12 June 2024, 211 participants from 32 medical centres in China were randomised (2:2:1:1) to receive double-blind, once-weekly ecnoglutide (0.6 mg [n = 69] or 1.2 mg [n = 71]) or volume-matched placebo (0.6 mg [n = 36] or 1.2 mg [n = 35]) for 24 weeks. The randomisation, stratified by baseline HbA1c (≤8.5% or >8.5%), was conducted via an interactive web response system. Ecnoglutide and placebo were identical in appearance to achieve masking. The trial was completed. All randomised participants received ≥1 dose of the assigned treatment and thus were included for analyses. At week 24, the least squares mean changes from baseline in HbA1c were -1.96% (95% CI -2.18 to -1.73) with ecnoglutide 0.6 mg and -2.43% (95% CI -2.65 to -2.20) with ecnoglutide 1.2 mg versus -0.87% (-1.09 to -0.65) with placebo. The estimated treatment differences versus placebo were -1.09% (95% CI -1.40 to -0.77; p = 0.0003) with ecnoglutide 0.6 mg and -1.56% (95% CI -1.87 to -1.24; p < 0.0001) with ecnoglutide 1.2 mg. Ecnoglutide represents a potential monotherapy option for T2DM. This trial was registered at clinicaltrials.gov with the registration number NCT05680155.

Objective To investigate the association between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) and cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (T2DM), and to evaluate their predictive value. Methods A total of 728 T2DM patients who were hospitalized in the Affiliated Suqian Hospital of Xuzhou Medical University between January 2023 and April 2025 were enrolled. All participants were assessed for CAN using cardiovascular autonomic reflex tests (CARTs) and then divided into a CAN group (n=352) and a non-CAN group (n=376). Clinical characteristics and laboratory parameters were compared between the two groups. Spearman correlation analysis was used to assess the relationships between NLR, PLR, MLR, and CART parameters. Logistic regression analysis was performed to identify independent risk factors for CAN. Receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) were used to evaluate the predictive performance of NLR and PLR for CAN in T2DM patients. Results Compared with the non-CAN group, patients in the CAN group had significantly higher age, duration of T2DM, glycated hemoglobin (HbA1c), NLR, PLR, and MLR levels, as well as higher prevalence of hypertension, coronary heart disease, diabetic nephropathy, diabetic retinopathy, and diabetic peripheral neuropathy (all P<0.05). In contrast, alanine aminotransferase levels were significantly lower in the CAN group (P<0.05). Spearman correlation analysis showed that NLR, PLR, and MLR were negatively correlated with deep breathing heart rate variability, Valsalva ratio, and 30∶15 R-R interval ratio (r<0, all P<0.05). Logistic regression analysis demonstrated that NLR, PLR, age, duration of T2DM, HbA1c, and diabetic retinopathy were independent risk factors for CAN in T2DM patients. ROC curve analysis showed that the AUCs of NLR, PLR, and their combination for predicting CAN were 0.775, 0.720, and 0.783, respectively. Conclusions NLR and PLR are closely associated with the occurrence of CAN in T2DM patients and have potential predictive value. Their combined assessment further improves predictive performance.

BackgroundMetabolic and bariatric surgery (MBS) is an established treatment for severe obesity, but its role in Asian patients with mild obesity (body mass index [BMI] 27.5-32.5 kg/m²) remains controversial due to limited mid-term evidence. This study evaluated the ≥3-year outcomes of MBS in this population compared with patients with BMI ≥32.5 kg/m².ObjectiveTo evaluate the mid-term (≥3 years) efficacy and safety of MBS in Asian patients with mild obesity, compared with those with BMI ≥MIhe kg/m².MethodsIn this retrospective cohort study, 26 patients with mild obesity and 76 matched patients with higher BMI underwent MBS between 2013 and 2020. Outcomes included percent total weight loss (%TWL), metabolic control, remission of obesity-related comorbidities, and postoperative complications. The primary composite endpoint was defined as glycated hemoglobin <6.5%, low-density lipoprotein cholesterol <2.6 mmol/L, systolic blood pressure <130 mmHg, and homeostasis model assessment of insulin resistance <2.5 mmol/L, μU/mL.ResultsAt a mean follow-up of approximately 5 years, the mild obesity group achieved lower %TWL than the higher-BMI group (approximately 20% vs 26%, P < 0.05). Despite this, the rate of achieving the composite metabolic endpoint was comparable (30.7% vs 27.6%, P = 0.76). Both groups demonstrated sustained improvements in glycemic control, lipid profile, blood pressure, and insulin resistance. Remission of type 2 diabetes, hypertension, hyperuricemia, and metabolic-associated fatty liver disease increased significantly in both groups (all P < 0.05). Notably, a substantially greater proportion of patients in the obesity group achieved normalization of body weight (BMI <24 kg/m²). Complication rates were low and comparable.ConclusionIn Asian patients, MBS appears safe and provides durable metabolic benefits across BMI categories. Despite losing less weight, those with mild obesity achieved similar cardiometabolic improvements and were more likely to reach a normal BMI. These findings are preliminary. Future research should prioritize large, multicenter studies focusing on the BMI 27.5–30 kg/m² subgroup without advanced metabolic disease, randomized trials comparing surgery with current pharmacotherapies, and long-term studies tracking hard cardiovascular endpoints.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become an important option in clinical use for type 2 diabetes due to their dual benefits of glycaemic management and metabolic improvements. Efsubaglutide alfa, a novel long-acting GLP-1RA, was developed for sustained glycaemic management. This study aimed to confirm its recommended clinical dose and evaluate its efficacy and safety in drug-naive individuals with type 2 diabetes that was inadequately managed through lifestyle interventions. This two-stage Phase IIb/III trial employed an operationally seamless adaptive design and enrolled adults who had been newly diagnosed with type 2 diabetes and whose diabetes was inadequately managed by diet and exercise. In the Phase IIb stage, participants were randomised in a 2:2:2:1 ratio to receive once-weekly subcutaneous injections of efsubaglutide alfa (1, 2 or 3 mg) or placebo for 12 weeks. Based on an interim analysis, two recommended Phase III doses (RP3Ds) were selected by an independent data monitoring committee. In the Phase III stage, participants were randomised in a 2:2:1 ratio to receive efsubaglutide alfa at one of the two RP3Ds or to receive placebo. Participants, investigators and sponsors were masked to drug/placebo allocation throughout the trial. The primary endpoint was the change in HbA1c from baseline to week 24. Secondary endpoints included changes in body weight and metabolic parameters at weeks 24 and 52. Safety was monitored throughout. In the Phase IIb stage, 140 participants were randomised to efsubaglutide alfa (1 mg, n=41; 2 mg, n=39; 3 mg, n=41) or placebo (n=19). Based on interim analysis, 1 and 3 mg were selected as the RP3Ds. In the Phase III stage, 297 participants were randomised to efsubaglutide alfa (1 mg, n=118; 3 mg, n=117) or placebo (n=62). At week 24, the HbA1c reductions from baseline were −18.91 mmol/mol (1.73

Introduction and Objective: Efsubaglutide Alfa (Suba) is a novel long-acting GLP-1RA. This post hoc analysis of T2D patients in trials investigating the efficacy of Suba’s monotherapy or combined with metformin, stratified by baseline (BL) characteristics. Methods: Patients aged ≥18 years, were randomized to receive 24-week Suba 1 mg, 3 mg, or placebo as monotherapy (Mean baseline HbA1c: 8.73% ± 0.72%) or co-administered with metformin (8.67% ± 0.75%). The estimated change from BL in HbA1c was analyzed stratified by BL characteristics, including age, BMI, gender, and HbA1c. Results: Total of 796 patients were evaluated, whose baseline characteristics were similar across all subgroups. Greater reductions in HbA1c were observed with Suba, nevertheless as monotherapy or in combination with metformin, across all BL subgroups, with significantly higher proportion of patients achieved HbA1c <7% and a metabolic composite endpoint compared to placebo. Conclusion: Significant reductions in HbA1c were achieved with Suba treatment, the monotherapy and the combined therapy, nevertheless their age, BMI, gender, and HbA1c. Y. Xu: Employee; Innogen Pharmaceutical Co., Ltd. Y. Duan: Employee; Innogen Pharmaceutical Co., Ltd. L. Zhang: Consultant; Innogen Pharmaceutical Co., Ltd. Q. Zhou: None. Y. Li: None. D. Zhu: Consultant; Innovent Biologics. W. Jia: None. Q. Wang: Employee; Innogen PharmaceuticalCo., Ltd. This study was sponsored by Innogen Pharmaceutical Co. Ltd.

Introduction and Objective: Mazdutide (MAZ) is a once-weekly GLP-1 and glucagon receptor dual agonist in development for type 2 diabetes (T2D). This trial assessed the efficacy and safety of MAZ vs placebo (PBO) in patients with T2D inadequately controlled by diet and exercise alone. Methods: In this randomized, 24-week double-blind, placebo-controlled phase 3 trial, 320 patients with T2D (mean baseline HbA1c 8.24%, age 50.4 yrs, diabetes duration 1.9 yrs, body weight 77.7 kg) were randomised 1:1:1 to receive MAZ 4 mg, 6 mg or PBO. Primary endpoint was mean change in HbA1c from baseline at week 24. Secondary endpoints included proportion of patients achieving HbA1c and weight reduction targets and mean percentage change in weight from baseline at week 24. Results: At week 24, MAZ was superior to PBO in mean HbA1c change from baseline (LSM treatment difference: −1.43% [95% CI −1.73, −1.13] for MAZ 4 mg; −2.02% [−2.32, −1.72] for MAZ 6 mg; both p<0.0001). MAZ was superior to PBO in proportion of patients achieving HbA1c <7.0%, weight reduction ≥5%, both HbA1c <7.0% and body weight reduction ≥5%, as well as mean percentage change in weight from baseline at week 24 (Table). The most common adverse events were gastrointestinal and mostly mild to moderate in severity. No severe hypoglycemia was reported. Conclusion: In Chinese patients with T2D, MAZ as monotherapy demonstrated robust and clinical meaningful HbA1c and body weight reduction. D. Zhu: Consultant; Innovent Biologics. J. Zhao: None. H. Cai: None. X. Chu: Consultant; Innovent Biologics. S. Xiu: Consultant; Innovent Biologics. C. Song: Consultant; Innovent Biologics. Z. Cheng: None. H. Cao: None. H. Jiang: None. L. Zhang: None. F. Xue: None. H. Deng: Employee; Innovent Biologics. H. Li: None. L. Li: Employee; Innovent Biologics. Stock/Shareholder; Innovent Biologics. L. Qian: Employee; Innovent Biologics. Innovent Biologics, Inc.

Background:Type 2 diabetes (T2D) is a considerable and growing burden in the Chinese population, and affected adults are at high risk of developing chronic kidney disease (CKD). This subgroup analysis of the FIGARO-DKD trial explored the cardiovascular and kidney benefits of finerenone in Chinese patients with CKD and T2D on optimized renin-angiotensin system blockade. Methods:Patients with urine albumin-to-creatinine ratio (UACR) ≥30-<300 mg/g and estimated glomerular filtration rate (eGFR) ≥25-≤90 mL/min/1.73 m2, or UACR ≥300-≤5000 mg/g and eGFR ≥60 mL/min/1.73 m2, were randomized to finerenone or placebo. The primary cardiovascular composite outcome was time to cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure. The secondary kidney composite outcome was time to kidney failure, sustained eGFR decline ≥40% from baseline, or kidney-related death. Results:A total of 325 Chinese patients were included. Finerenone resulted in a numerical decrease in the risk of the cardiovascular composite outcome (hazard ratio 0.91; 95% confidence interval 0.50-1.67) and a significantly reduced risk of the key secondary kidney outcome (hazard ratio 0.48; 95% confidence interval 0.29-0.79; p = 0.0029). The incidence of investigator-reported hyperkalemia was high across both treatment arms. Nevertheless, the incidence of hyperkalemia leading to hospitalization and treatment discontinuation was low across treatment arms. Conclusions:Finerenone significantly reduced the composite kidney outcome, showed a trend to reduce cardiovascular outcomes, and demonstrated an acceptable safety profile in Chinese patients.

Background Diabetes, a chronic disease necessitating long-term treatment and self-management, presents significant challenges for patients who spend most of their treatment time outside of hospitals. The potential of digital therapeutics for diabetes has garnered recognition from different organizations. Although some prior studies have demonstrated successful reductions in patients’ blood glucose levels and body weight through digital diabetes programs, many studies were limited by including patients with prediabetes, including patients treated with mostly premixed insulin, or evaluating user engagement outcomes rather than clinical outcomes. Consequently, limited evidence remains regarding the effectiveness of health management mobile apps specifically designed for patients with type 2 diabetes mellitus (T2DM) initiating basal insulin (BI). Based on this, a data-based and artificial intelligence management system named “TRIO” was developed to provide patients with more personalized intervention methods in stages, in groups, and around the clock. TRIO assists doctors and nurses in achieving better blood glucose controls, truly carries out standardized management around patients, and allows them to have a higher quality of life. TRIO represents the 3 essential pillars in comprehensive diabetes management: physician, nurse, and patient. Objective This prospective observational study evaluated the effectiveness and safety of the TRIO optimal health management program for patients with T2DM initiating BI therapy in a real-world setting. Methods Patients aged 18-85 years with inadequate glycemic control (baseline hemoglobin A1c [HbA1c] ≥7%) starting BI therapy were enrolled in outpatient and inpatient settings. The study lasted 3 months, with health education and phone-based follow-up assessments. Data collected included patient characteristics, medical history, baseline diabetes conditions, treatment compliance, glycemic control, and safety indicators. Results A total of 199,431 patients were included, and 118,134 patients completed the 3-month follow-up between December 1, 2019, and December 31, 2021, involving 574 hospitals in China. The mean baseline HbA1c was 9.2%, the mean duration of diabetes was 7.3 years, and 80.4% (1,59,930/1,98,969) of patients were using BI with oral antihyperglycemic drugs. After the intervention, mean HbA1c decreased by –2.59% from baseline, with 55.6% (28,858/51,912) achieving the target HbA1c level of <7%. Patients who set lower fasting plasma glucose goals (<6.1 mmol/L) showed more significant HbA1c reductions (P<.001) and higher target achievement than those with fasting plasma glucose goals of ≥6.1 mmol/L. Factors such as complications, diabetes duration, and baseline HbA1c levels influenced the magnitude of HbA1c reduction. The presence of complications, shorter diabetes duration, and higher baseline HbA1c were significantly associated with increased hypoglycemia incidence risk (all P<.05). Conclusions The TRIO optimal health management program effectively improved glycemic control in patients with T2DM initiating BI therapy. Individualized treatment approaches considering patient characteristics and glycemic goals are vital for optimal outcomes.

OBJECTIVE:To assess the effect of dapagliflozin plus calorie restriction on remission of type 2 diabetes. DESIGN:Multicentre, double blind, randomised, placebo controlled trial. SETTING:16 centres in mainland China from 12 June 2020 to 31 January 2023. PARTICIPANTS:328 patients with type 2 diabetes aged 20-70 years, with body mass index >25 and diabetes duration of <6 years. INTERVENTIONS:Calorie restriction with dapagliflozin 10 mg/day or placebo. MAIN OUTCOME MEASURES:Primary outcome: incidence of diabetes remission (defined as glycated haemoglobin <6.5% and fasting plasma glucose <126 mg/dL in the absence of all antidiabetic drugs for at least 2 months); secondary outcomes: changes in body weight, waist circumference, body fat, blood pressure, glucose homoeostasis parameters, and serum lipids over 12 months. RESULTS:Remission of diabetes was achieved in 44% (73/165) of patients in the dapagliflozin group and 28% (46/163) of patients in the placebo group (risk ratio 1.56, 95% confidence interval (CI) 1.17 to 2.09; P=0.002) over 12 months, meeting the predefined primary endpoint. Changes in body weight (difference -1.3 (95% CI -1.9 to -0.7) kg) and homoeostasis model assessment of insulin resistance (difference -0.8, -1.1 to -0.4) were significantly greater in the dapagliflozin group than in the placebo group. Likewise, body fat, systolic blood pressure, and metabolic risk factors were significantly more improved in the dapagliflozin group than in the placebo group. In addition, no significant differences were seen between the two groups in the occurrence of adverse events. CONCLUSION:The regimen of dapagliflozin plus regular calorie restriction achieved a much higher rate of remission of diabetes compared with calorie restriction alone in overweight or obese patients with type 2 diabetes. TRIAL REGISTRATION:ClinicalTrials.gov NCT04004793.

Diabetes has become a severe health threat in China, owing to its increasing prevalence, long-term morbidity, and mortality. This study evaluated the association between adherence to blood glucose self-monitoring guidance and glycemic control among patients with T2DM A 12-week mHealth-based prospective cohort study was conducted. Patients received recommendations on self-monitoring of blood glucose (SMBG) testing frequencies and uploaded testing results through smart glucose monitoring devices. initiating basal insulin in China. A 12-week mHealth-based prospective cohort study was conducted. Patients received recommendations on self-monitoring of blood glucose (SMBG) testing frequencies and uploaded testing results through smart glucose monitoring devices. A total of 14,084 patients from 242 hospitals were enrolled. Most patients (73.3%) had <4 times SMBG testing per week, and these patients were significantly older, mostly males, had a longer duration of diabetes, lower income and received less education than patients with better adherence. Larger HbA1c reduction was observed in patients with 4-7 and ≥7 times of SMBG testing per week compared to patients with <4 times of SMBG testing per week (LS mean difference [95% CI]: -0.10 [-0.18, -0.02], and -0.17 [-0.26, -0.08], respectively, and this was more prominent in patients with baseline HbA1c >9%. The benefit of improving adherence to SMBG guidance was consistently found for FBG reduction, HbA1c, and FBG target rate. The study demonstrated a positive relationship between adherence and glycemic control and identified patient characteristics with poorer adherence for further customization of mHealth.

Evidence-based treatment strategies for patients with cardiovascular disease and diabetes have been updated in recent years. However, substantial gaps remain between guideline recommendations and clinical practice, which justify the urgent need to improve the quality of care for patients with these conditions. The Chinese Society of Cardiology and the Chinese Society of Diabetes, in collaboration with the American Heart Association and the American Diabetes Association, designed the China Diabetes Cardiovascular project. The China Diabetes Cardiovascular project is a nationwide registry study aimed at improving the quality of care for patients with acute coronary syndrome and diabetes in China. Launched in 2021, this project has enrolled 36 hospitals across mainland China. Patients with a primary discharge diagnosis of comorbid acute coronary syndrome and diabetes will be eligible to participate. Pre-defined performance measures will be adopted to evaluate the quality of care for these patients. Multiple quality improvement strategies will be adopted, including providing monthly quality reports based on these measures, conducting a series of training courses, and distributing educational materials. A comprehensive dataset, encompassing patients’ characteristics, medical history, treatment before and during the current hospitalization, and discharge medications for secondary prevention, will be collected through a web-based data collection platform. This project has the potential to improve the quality of care and reduce the care disparities in the management of patients with these diseases. Moreover, with its comprehensive data collection, this project will provide a strong foundation for exploring key clinical questions.

Despite advances in type 2 diabetes (T2D) management, unmet needs remain for therapies that effectively control hyperglycaemia while addressing comorbid metabolic disorders1,2. Here we assessed the efficacy and safety of the dual glucagon receptor (GCGR)/glucagon-like peptide-1 receptor (GLP-1R) agonist mazdutide monotherapy versus placebo in Chinese adults with T2D controlled inadequately with diet and exercise alone. In this phase 3 trial, 320 participants (mean glycated haemoglobin A1c (HbA1c) of 8.24%, body mass index of 28.2 kg m-2 and diabetes duration of 1.9 years) were randomized 1:1:1 to receive weekly subcutaneous injections of mazdutide (4 mg or 6 mg) or placebo for 24 weeks, followed by a 24-week extended mazdutide treatment. At week 24, mazdutide significantly reduced HbA1c versus placebo (primary endpoint): -1.57% with mazdutide 4 mg and -2.15% with mazdutide 6 mg, versus -0.14% with placebo, with treatment differences of -1.43% and -2.02% (both P < 0.0001). Weight loss from baseline at week 24 occurred with -5.61% (4 mg) and -7.81% (6 mg) versus -1.26% (placebo) (both P < 0.0001). Furthermore, more participants with mazdutide achieved HbA1c < 7.0%, weight loss ≥ 5% (all P < 0.0001) and composite endpoints (HbA1c < 7.0% and weight loss ≥ 5%) versus placebo (P = 0.0006 for 4 mg; P < 0.0001 for 6 mg) at week 24. The most common adverse events-diarrhoea, decreased appetite and nausea-were consistent with GLP-1R agonists. These results establish mazdutide monotherapy as an effective intervention providing clinically meaningful glycaemic control and weight reduction alongside a favourable safety profile in this population.

In recent years, the prevalence of diabetes in China has increased significantly, and approximately 11.9% of Chinese adults had diabetes in 2020. Moreover, there are several rigorous challenges in diabetes prevention and glycaemic control, especially at the primary medical care level. In order to guide primary healthcare providers in providing comprehensive and continuous care to affected patients, the Office for Primary Diabetes Care of the National Basic Public Health Service Program and the Chinese Diabetes Society issued national guidelines for the prevention and control of diabetes at the primary care level in 2025. The management objects were adults with type 2 diabetes aged ≥18 years. The main contents include basic requirements for management, health management process, diagnosis, screening, evaluation, treatment, recognition and management of acute complications, traditional Chinese medicine, referral and health management and education.

Abstract Background The preservation or restoration of β cell function in type 1 diabetes (T1D) remains as an attractive and challengeable therapeutic target. Mesenchymal stromal cells (MSCs) are multipotent cells with high capacity of immunoregulation, which emerged as a promising cell-based therapy for many immune disorders. The objective of this study was to examine the efficacy and safety of one repeated transplantation of allogeneic MSCs in individuals with T1D. Methods This was a nonrandomized, open-label, parallel-armed prospective study. MSCs were isolated from umbilical cord (UC) of healthy donors. Fifty-three participants including 33 adult-onset (≥ 18 years) and 20 juvenile-onset T1D were enrolled. Twenty-seven subjects (MSC-treated group) received an initial systemic infusion of allogeneic UC-MSCs, followed by a repeat course at 3 months, whereas the control group (n = 26) only received standard care based on intensive insulin therapy. Data at 1-year follow-up was reported in this study. The primary endpoint was clinical remission defined as a 10% increase from baseline in the level of fasting and/or postprandial C-peptide. The secondary endpoints included side effects, serum levels of HbA1c, changes in fasting and postprandial C-peptide, and daily insulin doses. Results After 1-year follow-up, 40.7% subjects in MSC-treated group achieved the primary endpoint, significantly higher than that in the control arm. Three subjects in MSC-treated group, in contrast to none in control group, achieved insulin independence and maintained insulin free for 3 to 12 months. Among the adult-onset T1D, the percent change of postprandial C-peptide was significantly increased in MSC-treated group than in the control group. However, changes in fasting or postprandial C-peptide were not significantly different between groups among the juvenile-onset T1D. Multivariable logistic regression assay indicated that lower fasting C-peptide and higher dose of UC-MSC correlated with achievement of clinical remission after transplantation. No severe side effects were observed. Conclusion One repeated intravenous dose of allogeneic UC-MSCs is safe in people with recent-onset T1D and may result in better islet β cell preservation during the first year after diagnosis compared to standard treatment alone. Trial registration ChiCTR2100045434 . Registered on April 15, 2021—retrospectively registered, http://www.chictr.org.cn/

AIMS:This Phase 1 study aimed to evaluate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of single-dose subcutaneous Efsubaglutide Alfa, a novel glucagon-like peptide-1 receptor agonist (GLP-1RA), in healthy participants. MATERIALS AND METHODS:This randomised, double-blind, placebo-controlled, single-dose escalation study was conducted at a single centre. A total of 48 healthy adults were randomised (6:2) across six dose cohorts (0.375, 0.75, 1.5, 3, 6 and 9 mg) to receive Efsubaglutide Alfa or placebo. Safety, PK and PD parameters were assessed. RESULTS:Efsubaglutide Alfa exhibited dose-proportional PK, with a median Tmax of 47.5-71.7 h and a mean half-life (T1/2) of 121.4 h. Exposure increased linearly across doses (Cmax: 37.1-832.4 ng/mL, AUC0-∞: 8699.6-193446.6 ng/mL·h). No serious AEs occurred; mild-to-moderate gastrointestinal AEs (nausea, vomiting, decreased appetite) were the most common in Efsubaglutide Alfa-treated subjects. Post-dose, fasting plasma glucose transiently declined on Day 1, returned to baseline by Day 2, and remained within -0.8 to +1.9 mmol/L relative to baseline (within expected physiological variability) through Day 28. Fasting insulin and C-peptide levels slightly increased on Day 1, normalised by Day 2, and remained stable. At Day 2, OGTT revealed reduced glucose excursions in Efsubaglutide Alfa recipients (p = 0.0150 vs. placebo; AUC ~0.7 mmol/L·2 h lower), while insulin and C-peptide levels remained unchanged. Dose-dependent weight loss peaked at Day 4-7, with up to a 4.0% reduction (p < 0.0001) at the higher dose, followed by a gradual return towards baseline by Day 28. CONCLUSIONS:Efsubaglutide Alfa was well tolerated in healthy participants, with a favourable PK and PD profiles that support further clinical development in type 2 diabetes and metabolic disorders.