Background: China bears the world’s largest burden of type 2 diabetes, yet achievement of guideline-recommended cardiometabolic targets in routine care remains poor. Whether body-mass index (BMI) is associated with differences in 3B target achievement and treatment patterns across the BMI spectrum has not been systematically evaluated in a contemporary Chinese cohort. Methods: In this multicentre cross-sectional study, we analysed baseline data from 8,592 adults with type 2 diabetes enrolled in the iCaReMe China Registry between July, 2023, and March, 2024. BMI was classified as underweight, normal weight, overweight, or obese using Chinese-specific cutoffs. We assessed 3B target achievement—defined as simultaneous attainment of HbA1c lower than 7·0%, blood pressure lower than 130/80 mm Hg, and LDL-C lower than 2·6 mmol/L—across BMI categories, and examined associations using multivariable logistic regression and restricted cubic spline models. Findings: Among participants with complete data for all three outcome components, 3B target achievement ranged from 6·7% in normal-weight participants to 3·0% in obese participants. Compared with normal-weight participants, adjusted odds of 3B target achievement were lower in those with overweight (OR 0·69, 95% CI 0·55–0·86; P=0·001) and obesity (OR 0·37, 95% CI 0·27–0·51; P<0·001). Restricted cubic spline analyses showed an inverted U-shaped association between BMI and glycaemic target achievement, peaking near 22 kg/m², whereas blood-pressure target achievement declined monotonically with increasing BMI. Despite the greatest use of GLP-1 receptor agonists and SGLT2 inhibitors, obese participants had the lowest 3B target achievement. Underweight participants represented a clinically distinct subgroup characterised by poor glycaemic control, high insulin use, and the highest prevalence of macrovascular complications. Interpretation: In Chinese adults with type 2 diabetes, 3B target achievement was low across the BMI spectrum and lowest among those with obesity, despite greater use of newer glucose-lowering therapies. Underweight should not be assumed to indicate low cardiometabolic risk. These findings suggest that glycaemia-centred treatment alone is insufficient and support BMI-informed, multifactorial approaches to cardiometabolic risk management.

BACKGROUND:Endothelial dysfunction induced by elevated free fatty acids is a critical initiating event in diabetic macrovascular complications. While mitochondrial reactive oxygen species (mtROS) are key mediators of this lipotoxic injury, the specific contribution of mitochondrial Complex I dynamics and its associated redox regulation remains to be fully elucidated. METHODS:We investigated the therapeutic potential of targeting mitochondrial Complex I in lipotoxicity-induced endothelial injury. Using rotenone (a Complex I inhibitor) and NDUFS4 [NADH Dehydrogenase (Ubiquinone) Fe-S Protein 4]-targeting siRNA, we performed in vitro interventions in palmitic acid-treated human aortic endothelial cells and in vivo studies in high-fat diet (HFD)-fed mice. RESULTS:Palmitic acid triggered endothelial dysfunction accompanied by pronounced mitochondrial oxidative stress. Mechanistically, palmitic acid lowered the oxidised/reduced nicotinamide adenine dinucleotide (NAD+/NADH) ratio and increased NADH-linked Complex I activity, a redox state consistent with enhanced Complex I-linked ROS generation. Pharmacological (rotenone) or genetic (NDUFS4 knockdown) modulation of Complex I activity suppressed mtROS overproduction, improved NAD+/NADH balance, alleviated oxidative stress and improved endothelial function. In vivo, rotenone attenuated HFD-induced systemic metabolic disturbances and vascular oxidative stress while improving endothelial barrier integrity and angiogenic responses. CONCLUSIONS:Our study suggests that dysregulated mitochondrial Complex I activity may serve as an important contributor to lipotoxic endothelial injury. These findings support Complex I modulation as a potential strategy to mitigate free fatty acid-induced endothelial dysfunction in obesity- and diabetes-related vascular complications.

BACKGROUND:Performance of the uCGM 100 continuous glucose monitoring (CGM) system, featuring a 15.5-day, real-time, and factory-calibrated glucose sensor, is evaluated against venous plasma reference for adult participants (≥18 years) in a multicenter, prospective clinical study. METHODS:A total number of 60 participants were enrolled at three clinical sites in China, and each participant wore sensors on the back of each upper arm for 15.5 days. Three in-clinic visits, lasting eight hours during each visit, were conducted by each participant to perform multiple venous plasma glucose measurements using Biosen C-Line GP+ (EKF Diagnostics) Glucose/Lactate Measuring System. Venous plasma blood glucose sample tests covered the start, middle, and end wear of the sensor (day 1, days 3-5, days 7-9, days 11-13, or the last 24 hours). Analytic performance included accuracy such as ±20% or ±20 mg/dL (%20/20) agreement rate with reference values, and mean absolute relative difference (MARD) between CGM and reference values. RESULTS:A total of 11 576 matched data pairs (120 sensors) were analyzed. The overall MARD and %20/20 agreement rate for the CGM system was 7.6% and 95.5%, respectively, compared with venous blood reference. The %20/20 agreement remained consistently above 93% across wear days and glucose ranges. No serious adverse events were recorded. Usability survey showed 99.8% positive feedback, demonstrating good usability. CONCLUSIONS:The novel CGM system was proven to provide accurate and reliable glucose readings in adults with diabetes.

IntroductionGlucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for type 2 diabetes mellitus (T2DM) and may influence reward-related pathways, suggesting potential effects on nicotine dependence and smoking-related outcomes. Randomized evidence in patients with T2DM remains limited. This trial evaluates the effects of GLP-1RAs on nicotine dependence and smoking exposure and explores potential neural mechanisms using functional MRI (fMRI).Methods and analysisThis single-center, parallel-group randomized controlled trial will enroll 46 male adults with T2DM who are current smokers with Fagerström Test for Nicotine Dependence (FTND) score ≥4. Participants will be randomized (1:1) to receive a GLP-1RA or a dipeptidyl peptidase-4 inhibitor (DPP-4i) for 24 weeks as part of routine glucose-lowering therapy optimization. No structured smoking cessation counseling or smoking cessation pharmacotherapy will be provided by the research team. The primary endpoint is change in FTND score from baseline, assessed at weeks 1, 4, 8, 12, and 24. Secondary endpoints include changes in exhaled carbon monoxide (CO) and smoking cessation rate at weeks 12 and 24, and changes in metabolic parameters. Exploratory endpoints include changes in resting-state fMRI measures from baseline to week 24 and their associations with smoking- and metabolic-related outcomes.Trial statusRecruitment started in June 2025 and is ongoing. Clinical Trial RegistrationClinicalTrials.gov, identifier (NCT06924697).

Objectives To investigate the association between periodontitis, tooth loss, and asymptomatic carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM), and to explore whether this relationship persists in patients with low traditional cardiovascular risk factors. Materials and methods A cross-sectional study was conducted involving 306 hospitalized T2DM patients without symptomatic atherosclerotic disease. Carotid intima-media thickness (cIMT) and plaque presence were assessed via ultrasonography. Periodontal status was evaluated through clinical examination and panoramic radiography. Salivary levels of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and matrix metalloproteinase 9 (MMP-9) were measured by enzyme-linked immunosorbent assay (ELISA). Multivariable logistic regression was used to adjust for confounders including age, sex, smoking, low-density lipoprotein cholesterol (LDL-C), glycosylated hemoglobin (HbA1c), body mass index (BMI), and diabetes duration. Results Patients with cIMT ≥1 mm or carotid plaques had significantly higher clinic attachment loss (CAL) values, more tooth loss, and a higher prevalence of severe periodontitis (P<0.05). Multivariable analysis confirmed that severe periodontitis and increased tooth loss were independently associated with both cIMT ≥1 mm and carotid plaque presence. These associations remained significant even in subgroups with lower LDL-C, lower BMI, younger age, shorter diabetes duration, or better glycemic control. Salivary TNF-α levels were significantly elevated in patients with carotid atherosclerosis. Conclusion Severe periodontitis and tooth loss are significantly associated with asymptomatic carotid atherosclerosis in T2DM patients, including those with low conventional cardiovascular risk profiles. Salivary TNF-α may be linked to subclinical atherosclerosis in this population.

BACKGROUND:Primary aldosteronism (PA) carries excess cardiovascular risk not fully explained by hemodynamic load. While aldosterone promotes fibroblast activation experimentally, in vivo evidence linking adrenocortical activity with myocardial remodeling remains limited. This study integrated CXCR4 (C-X-C chemokine receptor type 4)-targeted 68Ga-Pentixafor positron emission tomography (PET)/magnetic resonance and FAP (fibroblast activation protein)-targeted 68Ga-FAPI (fibroblast activation protein inhibitor)-04 PET/cardiac magnetic resonance to evaluate the adrenal-cardiac axis in PA. METHODS:Eighty-two participants (40 with PA [21 aldosterone-producing adenoma (APA), 19 idiopathic hyperaldosteronism], 21 with essential hypertension, and 21 normotensive controls) underwent 68Ga-FAPI-04 PET/cardiac magnetic resonance; 48 concurrently underwent 68Ga-Pentixafor PET/magnetic resonance. Adrenal CXCR4 and myocardial FAPI uptake, as well as integrated volumetric-uptake burdens, were quantified and correlated with clinical and cardiac magnetic resonance indices. Eight patients with APA underwent follow-up imaging postadrenalectomy. RESULTS:Adrenal volume-adjusted CXCR4 signal served as a reliable marker of in vivo aldosterone burden and was significantly associated with adverse left ventricular remodeling, independent of blood pressure levels or hypertension duration. Myocardial 68Ga-FAPI-04 uptake was detected in 55% of patients with PA (APA 71.4%, idiopathic hyperaldosteronism 36.8%), compared with 19% of patients with essential hypertension and 0% of controls (P<0.001), localizing predominantly to the basal septum. Importantly, total adrenal volume-adjusted CXCR4 signal correlated with myocardial FAPI activity (r=0.38-0.64; all P<0.05) and cardiac magnetic resonance markers of remodeling, both of which were positively associated with aldosterone levels. At 5.2±1.2 months post-adrenalectomy, myocardial FAPI uptake in 8 patients with APA declined significantly (P<0.01), whereas late gadolinium enhancement and global cardiac function showed no significant change. CONCLUSIONS:Dual-tracer PET/magnetic resonance provided in vivo molecular evidence of a CXCR4-FAP-mediated adrenal-cardiac axis in PA, revealing cross-talk between adrenocortical function, aldosterone secretion, and myocardial fibroblast activation beyond blood pressure effects. FAPI PET demonstrated more severe myocardial activation in APA, with partial postadrenalectomy reversibility, underscoring the value of early diagnosis and timely surgical intervention. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06756737.

OBJECTIVE:To systematically evaluate the effects of mobile health (mHealth) technology interventions on body weight and liver enzyme levels in patients with nonalcoholic fatty liver disease (NAFLD). METHODS:Randomized controlled trials (RCTs) investigating mHealth interventions for NAFLD patients were retrieved from CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, Embase, and Web of Science databases from inception to March 2025. Data analysis was conducted using RevMan 5.2 software. RESULTS:Ten RCTs involving 1489 patients were included. The meta-analysis demonstrated that mHealth interventions significantly reduced body weight [standardized mean difference (SMD)=-1.93, 95% CI (-3.08, -0.77)], aspartate aminotransferase (AST) [SMD=-1.27, 95% CI (-2.01, -0.54)], and alanine transaminase (ALT) [SMD=-1.48, 95% CI (-2.20, -0.76)] compared with control groups (all P <0.05). CONCLUSION:This meta-analysis demonstrates that mHealth technology interventions are effective for weight loss and improvement of liver enzymes in patients with NAFLD, positioning them as a promising and scalable long-term management strategy.

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

Background Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Sodium-glucose cotransporter protein 2 inhibitors (SGLT2i) are antihyperglycemic agents that provide additional renal-protective effects in patients with DKD, independent of their glucose-lowering effects. However, the underlying mechanism remains unclear. This study hypothesized that SGLT2i could alleviate diabetic kidney injury by inhibiting ferroptosis and explored its potential mechanisms.Methods C57BL/6J mice were randomly divided into the control, DKD, DKD+dapagliflozin, and DKD+insulin treatment groups. Blood glucose levels and body weight were monitored. Renal function, tissue pathology, mitochondrial morphology and function, and lipid peroxidation biomarkers (lipid peroxidation [LPO], malondialdehyde [MDA], glutathione peroxidase 4 [GPX4], glutathione [GSH], and cystine transporter solute carrier family 7 member 11 [SLC7A11]) were evaluated. Human proximal tubule cells (HK2 cells) were exposed to high glucose alone or in combination with dapagliflozin. The mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) level, NAD+/NADH ratio (oxidized/reduced ratio of nicotinamide adenine dinucleotide), and lipid peroxidation were measured. In addition, the role of the β-hydroxybutyrate- Calcium/Calmodulin Dependent Protein Kinase Kinase 2 (BHB-CaMKK2) axis in mediating dapagliflozin regulating ferroptosis was examined.Results Dapagliflozin significantly ameliorated kidney injury in mice with DKD. Typical changes in ferroptosis, including lipid peroxidation and impaired antioxidant capacity, increased in mice with DKD and HG-treated HK-2 cells. Dapagliflozin significantly improves ferroptosis-related lipid peroxidation and mitochondrial dysfunction. Furthermore, dapagliflozin suppressed the expression of CaMKK2, a key ferroptosis regulator. Specific CaMKK2 inhibitors alleviated mitochondrial damage and ferroptosis, whereas a CaMKK2 agonist counteracted the protective effects of dapagliflozin against mitochondrial, antioxidant, and anti-ferroptosis effects. In addition, dapagliflozin increased BHB production, which mediates its nephroprotective effects.Conclusion Dapagliflozin improves DKD by inhibiting ferroptosis, promoting BHB production, and regulating CaMKK2.

This article describes the study rationale and design of the real-world multicenter registry study iCaReMe China. iCaReMe China is a prospective, multicentric, observational registry study aiming to understand the real-world characteristics of patients with type 2 diabetes (T2D) and/or hypertension (HTN) [combined chronic kidney disease (CKD)] and/or heart failure (HF) and/or CKD, which may provide some evidence for improving quality of care and outcomes of T2D and/or HTN and/or HF and/or CKD in China. A total of approximately 19,000 subjects will be recruited from 110 participating sites in China. Patients will be enrolled in four disease cohorts based on the primary disease conditions. The primary outcome is to describe the sociodemographic, clinical characteristics, disease management patterns, healthcare resource utilization, and clinical outcomes. iCaReMe China aims to describe the real-world characteristics and treatment patterns of patient with T2D and/or HTN (combined CKD) and/or HF and/or CKD. The data from this prospective registry study will facilitate a better understanding of management strategies, the variations across and within different regions, and associated patient outcomes in China. ChiCTR2300073764.

Gut microbiota contributes to prediabetes progression, however, whether microbiota features can guide targeted prevention and treatment for diabetes requires validation through large-scale clinical trials. Here, in a randomized, open-label trial, we randomly assigned 802 prediabetic subjects to a usual care control group (patient education and dietary recommendations, n = 393) or a dietary fiber intervention group (n = 409) for 6 months. The primary outcome was the percentage change in whole-blood HbA1c, and secondary outcomes were the changes in other glucose, insulin, lipid, liver and kidney function, and anthropometric parameters. There were no statistically significant differences in the primary and secondary outcomes between groups. In post-hoc analysis, we reclassified subjects into four clusters using a multivariate clustering model based on age, BMI, HbA1c, HOMA2-IR and HOMA2-B. These clusters differed in metabolic status, risks of diabetes and its complications, gut microbiome and serum metabolites. Notably, dietary fiber improved glycemic control in Clusters 3 and 4, but not in Clusters 1 and 2, consistent with observed gut microbiota alleviations. By using a LightGBM machine learning model, we calculated a microbiome-based clinical decision score to predict personalized fiber intervention responses and identified individuals who can get glycemic benefits. In conclusion, our study suggests that the gut microbiota response influences the effectiveness of dietary fiber intervention and provides a clinically applicable model to guide microbiome-targeted personalized medicine for prediabetes. Clinical Trial Registry: ChiCTR1900027663. Here, in a large-scale clinical trial, the authors associate gut microbiota composition and metabolic status with effectiveness of dietary fiber intervention in prediabetes, and provide a clinically applicable model to guide microbiome-targeted personalized medicine.

Introduction and Objective: The severe epidemic of Type 2 diabetes mellitus (T2DM) poses major global health threat in China. A comprehensive understanding of the current status of T2DM is paramount. In order to provide current and overall real-world data on clinical characteristics, treatment patterns and outcomes in patients with T2DM in China, we conducted iCaReMe China Registry. Methods: This is an ongoing prospective, multicentric, observational registry. Adult patients with T2DM were recruited from participating sites in China from July 2023 to March 2024. Consecutive patients attending the clinics for their routine health care visits were assessed for eligibility. The primary outcome is to describe the socio-demographic, clinical characteristics, disease management patterns, healthcare resource utilization, and clinical outcomes. Results: A total of 9,000 participants with T2DM (mean age 54.8±12.2 years old, mean diabetes duration 6.0±7.0 years) were enrolled from 60 hospitals in China. The mean level of HbA1c was 8.5±2.2%. 43.9%, 42.8%, and 10.7% of the patients reported comorbid hypertension, dyslipidemia, or chronic kidney disease. About 14.9% and 16.7% of them reported history of micro- and macro-vascular complications. 36.5%, 72.2%, and 36.1% of patients achieved the individual target goals for control of blood glucose (HbA1c<7%), blood pressure (SBP<130mmHg and DBP<80mmHg), and blood lipids (low density lipoprotein cholesterol<2.6mmol/L), respectively. Only 9.6% of patients achieved all 3 therapeutic targets. Conclusion: This study outlined the current status of glycemic control, blood pressure control, lipid control, and comorbidities in patients with T2DM in China, which suggesting urgent need of comprehensive management of diabetes. Adoption of cardiorenal protective therapies is crucial for optimization of clinical outcomes in patients with T2DM. W. Yang: None. X. Cai: None. B. Feng: None. M. Liu: None. Y. Li: None. N. Tong: None. L. Ji: None.

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.

Introduction and Objective: The global prevalence of type 2 diabetes mellitus (T2DM) is widely recognized to be on the rise. It is of great significance to reveal the current status of antidiabetic therapy in patients with T2DM. Methods: “Real-world Multicenter Registry to Determine Management and Quality of Care of Patients With Type 2 Diabetes in China” (iCaReMe China) is a prospective, multicentric, observational registry study. The study enrolled a total of 9,000 adults with T2DM from 60 hospitals in China from 2023 July to 2024 March, collecting demographic information, treatment patterns, complications, physical examination and laboratory test results. Results: Of the 9,000 participants enrolled, 99.2% were treated with antidiabetic medication, among which, 28.5% of the patients received monotherapy, and 71.5% of them received combination therapy. Metformin was the most frequent antidiabetic medication (59.5%), followed by SGLT2 inhibitor (38.9%), insulin (36.8%), α-glycosidase inhibitor (29.2%), DPP-4 inhibitor (16.8%), GLP-1 receptor agonist (14.9%), sulphonylurea (9.4%), and thiazolidinedione (5.2%). Compared with patients without diabetic complications, higher user percentage of SGLT2 inhibitor (46.9% vs 37.3%, P<0.001; 42.7% vs 38.4%, P=0.002), GLP-1 receptor agonist (20% vs 14%, P<0.001; 17.4% vs 14.4%, P=0.003), insulin (53.9% vs 33.8%, P<0.001; 46.2% vs 34.9%, P<0.001), α-glycosidase inhibitor, DPP-4 inhibitor and sulphonylurea were observed respectively in patients with microvascular and macrovascular diabetic complications. Conclusion: iCaReMe China demonstrated descriptive data on antidiabetic medication treatment patterns in Chinese patients with T2DM. Metformin is the most commonly used antidiabetic medication in Chinese patients with T2DM. The patients with microvascular and macrovascular diabetic complications were more likely to use SGLT2 inhibitors and GLP-1 receptor agonists. H. Wu: None. X. Cai: None. W. Yang: None. B. Feng: None. Y. Li: None. M. Liu: None. N. Tong: None. L. Ji: None.

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.

AIM:The "Real-World Multicenter Registry to Determine Management and Quality of Care of Patients With Type 2 Diabetes in China" (iCaReMe China) aims to generate contemporary evidence in Chinese type 2 diabetes mellitus (T2DM) patients. MATERIALS AND METHODS:This is a prospective, observational, multicentric registry study with 19 000 subjects from 110 hospitals recruited in China. Adults diagnosed with T2D and/or hypertension (HTN) (combined chronic kidney disease [CKD]), and/or heart failure (HF) and/or CKD were included. Data were collected every 6 months. RESULTS:In this article, we reported the findings from the baseline T2DM cohort, comprising 9000 patients recruited from 60 hospitals. The mean HbA1c level was 8.5 ± 2.2%, with 29.0% of them achieving the target HbA1c goal of <7.0%. The average blood pressure was 131/81 mmHg, with merely 27.8% reaching the target goal of blood pressure below 130/80 mmHg. The mean concentration of low-density lipoprotein cholesterol (LDL-C) was 2.8 ± 1.0 mmol/L, with 43.0% of the patients achieving an LDL-C level below 2.6 mmol/L. Only 5.0% of the patients achieved all three control targets for HbA1c, blood pressure and LDL-C. CONCLUSION:The registry demonstrated suboptimal control rates for cardiovascular risk factors among Chinese T2DM patients, underscoring the imperative need for implementing guideline-directed management.

Aim:The aim of this study was to compare the efficacy and safety of fixed-dose combination (FDC) of pioglitazone and metformin supplemented with dapagliflozin (test group) with those of basal insulin supplemented with metformin (control group) in patients with inadequately controlled type 2 diabetes mellitus (T2DM). Methods:This 16-week, prospective, randomized, open-label study enrolled patients aged 18-75 years with glycated hemoglobin (HbA1c) levels between ≥ 8% and ≤ 11%. The primary endpoint was the proportion of patients who achieved HbA1c < 7% at week 16 without hypoglycemia or weight gain. The secondary endpoints included blood glucose, lipid profile, body weight, body mass index, inflammatory markers, bone Gla-protein, liver enzymes, and patient satisfaction. Results:Among the full analysis set of 147 participants, no significant difference was observed in the primary endpoint between the test group and the control group. However, the test group had a higher percentage of patients who achieved HbA1c <7% at week 16 without hypoglycemia and experienced a weight loss of ≥3% (31.51% vs 13.51%, P=0.009). Patients in the test group whose BMI≥24 kg/m2 also achieved a substantial achievement rate (36.73% vs 15.79%, P=0.014). The test group also exhibited a greater reduction in body weight and improvements in 2-hour postprandial glucose level, systolic blood pressure, and lipid profile. Notably, combination therapy did not increase the risk of hypoglycemia or weight gain. Patients in the test group were more satisfied than those in the control group with continuing to accept pioglitazone/metformin FDC combined with dapagliflozin. Conclusion:In the absence of contraindications, pioglitazone/metformin FDC supplemented with dapagliflozin may serve as a safe and effective alternative to basal insulin combined with metformin for rectifying inadequate glucose control, as the former enables metabolic improvements without compromising safety. Chinese Clinical Trial Registry Number:CHiCTR2000036076. https://www.chictr.org.cn/showproj.html?proj=58825.