AIMS:To compare the efficacy and safety of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) with insulin degludec plus insulin aspart (IDegAsp) by baseline age, Type 2 diabetes (T2D) duration and glycated haemoglobin (HbA1c) in the Soli-D study. MATERIALS AND METHODS:In Soli-D, Chinese adults with T2D suboptimally controlled on oral antidiabetic drugs (OADs) were randomized to iGlarLixi or IDegAsp for 24 weeks. These post hoc analyses evaluated glycaemic efficacy, insulin dose, body weight and hypoglycaemia outcomes in subgroups defined by baseline age (< 65, ≥ 65 years), T2D duration (< 10, ≥ 10 years) and HbA1c (≥ 7% to ≤ 8% [≥ 53 to ≤ 64 mmol/mol], > 8% to ≤ 9% [> 64 to ≤ 75 mmol/mol], > 9% [> 75 mmol/mol]). RESULTS:Among 582 participants (iGlarLixi n = 291; IDegAsp n = 291), baseline age was < 65 years in 442 and ≥ 65 years in 140; T2D duration was < 10 years in 366 and ≥ 10 years in 216; and HbA1c was ≥ 7% to ≤ 8% in 205, > 8% to ≤ 9% in 209 and > 9% in 168. At Week 24, HbA1c reductions were greater with iGlarLixi versus IDegAsp, with no treatment-by-subgroup interactions for baseline age, T2D duration or HbA1c. Change in other glycaemic outcomes, insulin dose and body weight generally showed no interaction across subgroups. Total insulin daily doses during treatment and hypoglycaemia event rates were consistently lower with iGlarLixi versus IDegAsp in all subgroups. CONCLUSIONS:iGlarLixi provides improved glycaemic control at lower insulin doses with reduced risk of hypoglycaemia in Chinese adults with suboptimally controlled T2D on OADs, regardless of baseline age, disease duration or HbA1c.

AIMS:To compare the efficacy and safety of the fixed-ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) with premixed insulin degludec plus insulin aspart (IDegAsp) according to the injection time of IDegAsp. MATERIALS AND METHODS:The 24-week, multicentre, randomised, open-label Soli-D study enrolled Chinese adults with type 2 diabetes (T2D) suboptimally controlled with oral antidiabetic drugs (OADs). This exploratory analysis evaluated glycaemic efficacy, body weight, basal insulin daily dose and hypoglycaemia outcomes with once-daily iGlarLixi (injected before breakfast) versus IDegAsp (injected before breakfast, lunch or dinner). RESULTS:Of 582 participants, 291 received iGlarLixi, with injections self-administered before breakfast, and 291 received IDegAsp, with injections self-administered before breakfast (n = 139), lunch (n = 54) or dinner (n = 98). Glycated haemoglobin (HbA1c) reductions from baseline to Week 24 were greater with iGlarLixi than IDegAsp injected before lunch (least squares mean difference -0.24% [-2.3 mmol/mol]) or dinner (-0.29% [-3.2 mmol/mol]), and slightly greater than IDegAsp injected before breakfast (-0.12% [-1.3 mmol/mol]). Average 2-h postprandial glucose (2-h PPG) reductions were also greater with iGlarLixi than IDegAsp, regardless of injection time. iGlarLixi provided additional benefits, including reduced body weight, lower total insulin doses and less hypoglycaemia risk compared with IDegAsp in all injection-time subgroups. CONCLUSIONS:Once-daily iGlarLixi, injected before breakfast, was associated with improved HbA1c control and greater average 2-h PPG reductions compared with IDegAsp, regardless of injection time, in Chinese adults with T2D suboptimally controlled with OADs.

Introduction and Objective: Ph3 studies have compared iGlarLixi vs individual components (LixiLan-O-AP, LixiLan-L-CN) or IDegAsp (SoliD) in Asian PwT2D. This pooled analysis investigated the effect of iGlarLixi on PPG and SMPG derived time in range (dTIR). Methods: Changes in SMPG profile were analyzed in the pooled iGlarLixi vs control arms of LixiLan-O-AP, LixiLan-L-CN and SoliD. Results: Baseline characteristics are shown in Table 1. At EOT, iGlarLixi was associated with consistently greater reductions vs controls in the 7-point SMPG profile, except for pre-breakfast SMPG (Figure 1). LSM change in average 7-point, 2h PPG and dTIR was also greater with iGlarLixi vs comparators (Table 1). The % time of SMPG in range was higher with iGlarLixi vs controls. Conclusion: This analysis showed consistent PPG and dTIR benefits over 24h with iGlarLixi vs comparators in Asian people with T2D. Disclosure W. Lin: None. Q. Xu: None. H. Li: None. A. Alvarez: Employee; Current; Sanofi. F. Lauand: Employee; Current; Sanofi. L. Melas-Melt: None. L. Kang: Employee; Current; Sanofi China. Q. Du: Employee; Current; Sanofi China. X. Wang: Employee; Current; Sanofi China. H. Kuang: None. Funding These studies were funded by Sanofi (ClinicalTrials.gov identifiers: NCT03798054, NCT03798080, and NCT05413369). Professional medical writing support was provided by Sarah Greig, PhD, CMPP, of Springer Health+, and was funded by Sanofi.

Background:While the Updated Sydney System classifies Helicobacter pylori density together with inflammatory scores, the clinical relevance of bacterial load remains uncertain. This study aimed to assess the association between histological H. pylori density and the severity of gastric inflammatory activity. Methods:We performed a retrospective analysis of 1680 treatment-naive patients from a Chinese cohort (2022-2023). H. pylori density was categorized as low or high grades, with marked neutrophilic infiltration as the primary outcome. Multivariable logistic regression adjusted for potential confounders. Results:Among 2298 biopsy sites from 1680 patients (median age 52 years; 48.2% female), high H. pylori density showed no significant overall association with marked inflammation (all p > 0.050). While a significant inverse association was observed in non-atrophic antral single-site biopsies (adjusted odds ratio 0.52; 95% confidence interval 0.28-0.93), it was not reproduced in multi-site analyses. Increasing age was associated with a lower prevalence of severe antral inflammation. Conclusions:Histological H. pylori density might therefore not be a reliable marker of neutrophilic activity, although a significant inverse association observed in a single-site subgroup was not reproducible and may reflect sampling variability. Trial Registration:N/A.

AIMS:To evaluate the impact of iGlarLixi on the depth of glycaemic control, glycaemic variability (GV) and postprandial glucose (PPG) control versus insulin glargine 100 U/mL (iGlar) or lixisenatide (Lixi) in Asian Pacific individuals with type 2 diabetes (T2D). MATERIALS AND METHODS:A post hoc analysis was conducted of two phase 3 trials in individuals with suboptimally controlled T2D on oral antidiabetic drugs (LixiLan-O-AP) or basal insulin (LixiLan-L-CN). Outcomes were evaluated from baseline to end-of-treatment (EOT; Week 24 or 30, respectively). Using self-monitoring of blood glucose (SMBG) profiles, glycaemic control depth was assessed via derived time in tight range (dTITR; 3.9-7.8 mmol/L). GV was evaluated using standard deviation (SD) of SMBG, high blood glucose index (HBGI), mean absolute glucose (MAG), and mean amplitude of glycaemic excursions (MAGE). PPG at 0.5, 1, and 2 h was measured via standardised meal tests. RESULTS:From baseline to EOT, iGlarLixi provided greater increases in dTITR versus iGlar (least squares mean difference 15.03%) or Lixi (29.14%) in LixiLan-O-AP, and versus iGlar (15.93%) in LixiLan-L-CN. At EOT, > 50% dTITR rate was 67.2%, 41.1% and 26.5% with iGlarLixi, iGlar and Lixi in LixiLan-O-AP, respectively, and 53.6% and 26.4% with iGlarLixi and iGlar in LixiLan-L-CN. iGlarLixi provided generally greater reductions in SD of SMBG, HBGI, MAG, MAGE and 0.5-, 1- and 2-h PPG versus iGlar or Lixi and greater 2-h PPG < 10.0 mmol/L achievement rates at EOT. CONCLUSION:iGlarLixi improves dTITR, GV, and PPG control versus iGlar or Lixi in Asian Pacific individuals with T2D.

BACKGROUND:Although triple therapy plus bismuth (TTPB), comprising a proton pump inhibitor (PPI), two antibiotics, and bismuth, is widely used to eradicate Helicobacter pylori (H. pylori), eradication rates have been suboptimal. Potassium-competitive acid blockers (P-CABs) offer stronger and more stable gastric acid inhibition compared to PPIs. This study aimed to compare the efficacy, safety, and compliance of tegoprazan-based TTPB (TACB) vs. esomeprazole-based TTPB (EACB) in treatment-naïve patients with H. pylori infection. METHODS:In this nationwide, multicenter, double-blind, double-dummy, randomized controlled trial conducted from October 2022 to September 2023 across 41 centers in China, 561 eligible patients with H. pylori infection were randomized (1:1) to receive either TACB (tegoprazan 50 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth 220 mg) or EACB (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth 220 mg), all administered twice daily for 14 days. H. pylori eradication was assessed using the 13C-urea breath test at 4-8 weeks post-treatment. The primary endpoint was eradication rate based on the full analysis set (FAS). Statistical analysis included the chi-squared tests, with a predefined non-inferiority margin of -10%. RESULTS:In the FAS population, eradication rates were 93.5% (95% confidence interval [CI]: 89.9-96.1%) in the TACB group and 86.4% (95% CI: 81.9-90.2%) in the EACB group. The between-group difference was 7.0% (95% CI: 2.1-12.0%), indicating that tegoprazan-based TTPB was non-inferior to esomeprazole-based TTPB. Furthermore, superiority tests found a significantly higher eradication rate in tegoprazan group compared with esomeprazole group (P = 0.006). Similar results were observed in the per-protocol set. The incidence of treatment-emergent adverse events was comparable between groups (75.5% in TACB vs. 73.4% in EACB), with most events being mild and transient. Compliance was high in both groups (98.4% vs. 98.8%). CONCLUSION:TACB was non-inferior to EACB in H. pylori eradication efficacy, with similar safety and compliance profiles in Chinese treatment-naïve patients. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT05577468.

ABSTRACT Background Tetracycline has limited clinical application in Helicobacter pylori treatment because of difficulty in obtaining and increased adverse reactions. As a semisynthetic tetracycline, minocycline has demonstrated good potential for eradicating H. pylori infection. This study aimed to evaluate the efficacy and safety of 10‐day minocycline‐based quadruple therapy for H. pylori first‐line treatment. Methods In this prospective trial, treatment‐naïve adults with H. pylori infection received eradication therapy with rabeprazole 10 mg, minocycline 100 mg, amoxicillin 1000 mg, and bismuth potassium citrate 220 mg each given twice a day for 10 days. The primary outcome was the eradication rate. The secondary outcome was adverse effects. Eradication was confirmed by a negative urea breath test at least 6 weeks after the end of therapy. Results A total of 133 patients were included in the study. All of the patients completed the course of medication. We found that 10‐day minocycline‐amoxicillin quadruple therapy achieved an eradication rate of 83.5% (111/133, 95% CI 80.3%–86.7%) in intention‐to‐treat analysis and 90.2% (111/123, 95% CI 87.6%–92.8%) in per‐protocol analysis. The treatment‐emergent adverse events (TEAEs) were 15% (20/133), with the most common adverse event being dizziness (14/133, 10.5%). No severe adverse event was observed. Conclusions Ten‐day minocycline‐amoxicillin twice daily in bismuth‐containing quadruple therapy appears to be effective and safe for naïve H. pylori patients.

AIMS:To compare the efficacy and safety of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) with insulin degludec plus insulin aspart (IDegAsp) by β-cell function in exploratory analyses of the Soli-D study. MATERIALS AND METHODS:Soli-D was a 24-week, multicentre, randomised, open-label study in Chinese adults with uncontrolled type 2 diabetes (T2D) on oral antidiabetic drugs (OADs). We evaluated glycaemic efficacy, body weight, total insulin daily dose and hypoglycaemia outcomes with iGlarLixi versus IDegAsp by baseline fasting C-peptide and Homeostasis Model Assessment of β-cell function (HOMA-β) quartile measurements. RESULTS:Among 386 participants, change in glycated haemoglobin (HbA1c), fasting plasma glucose or postprandial glucose at Week 24 showed no interaction with fasting C-peptide or HOMA-β quartile. The difference in HbA1c change favoured iGlarLixi versus IDegAsp in fasting C-peptide quartile 1 (Q1; p = 0.045) and Q2 (p = 0.023) and HOMA-β Q1 (p = 0.025). The proportion of participants with HbA1c <7.0% (<53 mmol/mol) was higher with iGlarLixi in fasting C-peptide Q2 (p = 0.009) and HOMA-β Q1 (p = 0.013). Body weight benefits were observed with iGlarLixi in HOMA-β Q1 (p = 0.003). Total insulin daily dose was lower with iGlarLixi, showing interactions between C-peptide or HOMA-β quartile and insulin dose (U or U/kg; pint <0.001 for all). The event rate for any hypoglycaemia and American Diabetes Association Level 1 hypoglycaemia was lower with iGlarLixi in HOMA-β Q1 (p = 0.040 and 0.037). CONCLUSIONS:iGlarLixi provides improved glycaemic control at lower insulin daily doses compared with IDegAsp, regardless of C-peptide or HOMA-β levels, in Chinese people with uncontrolled T2D on OADs.

Accurate localization of early gastric cancer (EGC) remains challenging due to its morphological resemblance to gastritis. This study presents an artificial intelligence (AI)-assisted bedside diagnostic system to enhance EGC detection by visualizing gastric mucosal acidity. The ATPase H+/K+ transport β subunit (ATP4B), a key regulator of acid secretion, is progressively downregulated in gastric mucosal atrophy and intestinal metaplasia, and significantly reduced in EGC. A surface-enhanced Raman scattering (SERS) microarray is developed to map mucosal pH in 50 patient specimens (1,516 points), with founding compared to pathological images. A multi-model neural network is trained and validated internally on data from 40 patients (1,127 points) and externally validated on 10 patients (389 points). Using an optimal pH threshold of 6.845, the system achieved a strong correlation (R2 = 0.79) and low error (SSE = 71.83). External validation demonstrated 87.79% sensitivity, 85.04% specificity, 86.89% accuracy, and a κ score of 0.71. This system detected mild pH shifts in atrophic gastritis with intestinal metaplasia, but marked increases with EGC onset, and is able to predict inflammation prior to pathology confirmation. By integrating pH mapping with morphological features, this approach enables precise EGC localization, improves guidance for endoscopic submucosal dissection (ESD), and reduces false-positive diagnoses.