INTRODUCTION:The HSK16149-201/301 trial demonstrated short-term efficacy of the GABA analog crisugabalin for diabetic neuropathic pain. METHODS:In the current study, patients in both the crisugabalin and placebo control groups of the HSK16149-201/301 trial were invited to receive 80 mg/day crisugabalin for an additional 52 weeks. The primary end point was safety. The secondary end point was pain control as measured using the Short-Form McGill Pain Questionnaire (SF-MPQ). A total of 301 patients (mean age 59.7 years and males 58.1%) were enrolled. RESULTS:The rate of treatment-related adverse events (TRAEs) was 38.9% (117/301). The most frequent TRAEs were dizziness (27.2%), somnolence (8.3%), and peripheral edema (3.0%). The rate of Grade 3 or higher TRAEs was 1.7%. TRAEs led to dose reduction in 41 patients (13.6%), treatment interruption and discontinuation each in three patients (1.0%). At week 52, the mean difference in SF-MPQ pain rating index (PRI) and visual analog scale pain score from baseline was -2.5 (95% CI -2.9 to -2.0; paired t-test p < 0.0001) and -23.4 (95% CI -25.6 to -21.2; paired t-test p < 0.0001), respectively. The proportion of patients with SF-MPQ PPI score ≤ 1 increased by 19.0% over baseline (p < 0.0001). CONCLUSIONS:In summary, crisugabalin at 80 mg/day was well tolerated and demonstrated sustained analgesic activities. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT05890053.

Omentin-1 protein has protective effects against coronary artery disease (CAD). The Val109Asp polymorphism (rs2274907) in the Omentin-1 gene has been associated with CAD risk, but this relationship has not been investigated in patients with type 2 diabetes mellitus (T2DM). To investigate the association between the Omentin-1 Val109Asp polymorphism and CAD risk in Han Chinese patients with T2DM. This case-control study enrolled 465 Han Chinese patients with T2DM from July 2008 to September 2015. Participants were classified as CAD-positive (coronary stenosis > 50% in at least 1 major vessel, n = 249) or CAD-negative (n = 216). The Val109Asp polymorphism was genotyped using PCR-RFLP. Logistic regression analysis was performed to assess the association between genotypes and CAD risk, with adjustment for potential confounders including age, sex, smoking status, hypertension, dyslipidemia, diabetes duration, body mass index, and fasting glucose. The A allele frequency was higher in CAD patients than in controls (34.5% vs 27.5%; OR = 1.386; P = .026). Under the dominant model, TA/AA carriers had increased CAD risk compared with TT homozygotes (adjusted OR = 1.509, 95% CI: 1.025-2.222; P = .037). Stratified analyses showed that smokers carrying the A allele exhibited further elevated CAD risk (adjusted OR = 1.82, 95% CI: 1.02-3.27). The Omentin-1 Val109Asp polymorphism is associated with increased CAD risk in Han Chinese patients with T2DM under the dominant genetic model. Stratified findings suggest that smoking may further heighten CAD susceptibility among A-allele carriers. Integrating genetic and lifestyle factors may improve cardiovascular risk assessment in this population.

Background:Increased physical activity and reduced sedentary time are associated with lower risks of diabetes. However, their association with diabetic kidney disease (DKD) is unclear. This study aimed to assess this issue in the Chinese adults with diabetes. Methods:This multicenter, cross-sectional study included adults with diabetes from 40 hospitals across 26 diverse Chinese cities. Leisure-time physical activity (LTPA), housework physical activity (HPA), occupational physical activity (OPA), and sedentary time were assessed using a validated questionnaire. DKD was defined according to the NKF-K/DOQI guidelines. Associations between activity domains and DKD were examined using multivariable logistic regression, with subgroup, interaction, and sensitivity analyses to assess robustness. Results:A total of 4,979 patients with diabetes were included. After multivariable adjustment, those meeting the guideline-recommended amount of LTPA had lower odds of DKD (OR 0.79, 95% CI 0.68-0.91 for aerobic exercise; OR 0.69, 95% CI 0.50-0.96 for resistance exercise) compared with those not meeting recommendations. However, heavier HPA and larger OPA were associated with higher odds of DKD (OR 1.51 and 1.66, respectively). Moreover, longer daily sedentary time was associated with increased odds of DKD only in women (OR 2.10), but not in men. Further stratified analysis suggested that the association between LTPA and lower odds of DKD may be modified by HPA, OPA, or sedentary time. Conclusions:Among Chinese adults with diabetes, LTPA was associated with lower odds of DKD, whereas higher occupational and household physical activity showed positive associations, underscoring the differences in domain-specific physical activity in DKD prevention.

Background:Sustaining self-management is critical for optimizing clinical outcomes in individuals with type 2 diabetes mellitus (T2DM). Although digital health interventions (DHIs) have shown benefits for glycemic control and self-care, much of this evidence has focused on efficacy, and the behavioral mechanisms through which DHIs produce sustained effects remain insufficiently understood. Clarifying these mechanisms could inform the development of theory-driven interventions. Objective:This study examined the longitudinal behavioral pathways through which Artificial Intelligence-based Health Education Accurately Linking System, a WeChat (Tencent)-based digital health program, influences T2DM self-management, using the Extended Multi-Theory Model (MTM) of health behavior change. Methods:An explanatory sequential mixed methods prospective longitudinal cohort study was conducted among adults with T2DM (aged ≥18 y and proficient in WeChat use), recruited from 45 primary health care institutions in Beijing, China, between July 2023 and July 2024. Self-management behavior was assessed as the primary outcome using the Summary of Diabetes Self-Care Activities, and psychosocial determinants using the Extended MTM Scale and the Diabetes-related Skills Scale. Exploratory and confirmatory factor analyses assessed the construct validity of the Extended MTM Scale. Structural equation modeling examined longitudinal pathways among Artificial Intelligence-based Health Education Accurately Linking System users across baseline and 3, 6, and 12 months. For the qualitative phase, a purposive subsample was selected through maximum variation sampling based on baseline glycated hemoglobin; interviews were analyzed thematically until thematic saturation, and integrated with quantitative findings using a joint display. Results:Of the 406 enrolled participants, 391 completed baseline assessments. The Extended MTM Scale demonstrated a 6-factor, 22-item structure with excellent internal consistency (Cronbach α=0.928) and satisfactory construct validity. The structural equation modeling showed satisfactory fit (CFI=0.984, RMSEA=0.036). Changes in the social environment (β=0.23, 95% CI 0.07-0.38; P=.003) and physical environment (β=0.25, 95% CI 0.10-0.40; P=.001) at baseline, and diabetes-related skills at month 6 (β=0.16, 95% CI 0.03-0.29; P=.01), were directly associated with self-management behavior at month 12, whereas behavioral confidence and emotional transformation showed no significant direct effects. Social environment changes were indirectly associated with behavioral confidence through participatory dialogue at month 3 (β=0.20, 95% CI 0.04-0.36; P=.01; β=0.66, 95% CI 0.57-0.74; P<.001). Thematic analysis of 17 interviews identified 3 domains: environmental context, cognitive processes, and attitudes and skills. Environmental factors converged across both data strands, while qualitative data expanded on the cognitive and attitudinal processes underlying sustained self-management. Conclusions:This study is among the first to apply the Extended MTM framework to DHI-supported T2DM self-management, with environmental factors emerging as key drivers alongside selected cognitive, attitudinal, and skills-related processes. Complementing efficacy-focused research, it illuminates the psychosocial pathways underlying sustained self-management and refines the Extended MTM in digital health contexts. These insights can inform the design of theory-driven DHIs in primary care.

AIMS:To evaluate early glycaemic control (glycated haemoglobin [HbA1c] < 7.0% [<53.0 mmol/mol], fasting plasma glucose [FPG] ≤ 7.0 mmol/L or postprandial glucose [PPG] ≤ 10.0 mmol/L) with iGlarLixi versus insulin glargine 100 U/mL (Gla-100) in Asian people with suboptimally controlled type 2 diabetes (T2D) on oral antidiabetic drugs (OADs) in LixiLan-O-AP or basal insulin (BI) ± OADs in LixiLan-L-CN. MATERIALS AND METHODS:This post hoc analysis evaluated changes from baseline to Week 12 in HbA1c, FPG and PPG, hypoglycaemia incidence and the rates of target HbA1c achievement at Weeks 8 and 12. Median time to glycaemic control (i.e., time to 50% achieving target HbA1c, FPG or PPG) was also assessed. RESULTS:At Week 12, mean HbA1c reductions were greater with iGlarLixi versus Gla-100 in LixiLan-O-AP (-1.6% vs. -1.1% [-17.0 vs. -12.0 mmol/mol]) and LixiLan-L-CN (-1.3% vs. -0.5% [-13.9 vs. -5.4 mmol/mol]). PPG reductions were greater with iGlarLixi, while FPG reductions and hypoglycaemia incidence were similar. At Weeks 8 and 12, more participants had achieved target HbA1c or PPG with iGlarLixi versus Gla-100 in both studies. Median time to achieve HbA1c and PPG targets was shorter with iGlarLixi versus Gla-100 in LixiLan-O-AP (85 vs. 126 days and 84 vs. 167 days) and LixiLan-L-CN (85 vs. 239 days and 85 days vs. not estimable); median time to achieve FPG target was similar in LixiLan-O-AP (57 vs. 57 days) and LixiLan-L-CN (29 vs. 30 days). CONCLUSIONS:In Asian people with T2D suboptimally controlled on OADs or BI, iGlarLixi provided comprehensive earlier glycaemic control than Gla-100.

ABSTRACT Aim No studies have specifically examined the effects of finerenone in treating type 2 diabetes patients with chronic kidney disease (CKD) and microalbuminuria. This study aimed to evaluate the effectiveness of finerenone in this group of patients. Methods This retrospective real‐world study (ChiCTR2400087169) included type 2 diabetes outpatients with CKD from the Peking University First Hospital between March 2023 and March 2024. All patients in this study had a urinary albumin‐to‐creatinine ratio (UACR) of 30–299 mg/g. The effects of finerenone were assessed by comparing UACR, HbA1c, creatinine, serum potassium, eGFR, and blood pressure at baseline and after treatment. Results Sixty‐four patients (39 males and 25 females), with a median age of 65.75 years and a median duration of T2DM of 15.21 years, were included. The baseline median UACR was 100.50 mg/g, significantly decreased to 61.27 mg/g (P < 0.001) at 3 months and 62.49 mg/g (P < 0.001) at 6 months after treatment. None of the other parameters differed significantly. Finerenone alone or in combination with ABS inhibitors, SGLT2 inhibitors, or GLP‐1 agonists did not result in significant differences in UACR reduction. Patients with a >30% UACR decrease had significantly higher baseline systolic blood pressure (SBP) than those with a ≤30% decrease (P < 0.05). Furthermore, baseline SBP significantly decreased after 6 months of treatment in patients with a >30% UACR reduction (P < 0.05). Conclusions Finerenone is effective in treating type 2 diabetes with CKD and microalbuminuria. Improved SBP control leads to a greater UACR reduction.

Background To date, comprehensive data on the distribution of chronic kidney disease (CKD), the most prevalent comorbidity in diabetes, among Chinese adults with diabetes is lacking. Additionally, research gaps exist in understanding the association between CKD and cardiovascular health (CVH), an integrated indicator of lifestyle and metabolic control, within a nationwide sample of Chinese adults with diabetes. Methods A nationally community-based cross-sectional survey was conducted in 2018-2020. 58,560 residents diagnosed with diabetes aged 18-74 years nationwide were invited to participate, and 52,000 participants with complete CKD data were included in this study. CKD was identified by the presence of albuminuria (urine albumin-to-creatinine ratio >= 30 mg/g) and/or decreased estimated glomerular fi ltration rate (eGFR, <60 mL/min/ 1.73 m2). The latter was calculated using the CKD-EPI equation incorporating serum cystatin C and creatinine. CVH was evaluated using the " life ' s essential 8" (LE8) score, which ranged from 0 to 100 and included 8 components: diet, sleep duration, physical activity, nicotine exposure, hemoglobin A1c, blood pressure, non-high-density lipoprotein cholesterol, and body mass index. The total LE8 scores were categorized into low (0-49), middle (50-79), and high (80-100) according to the American Heart Association. The associations of albuminuria and decreased eGFR with potential associated factors, including CVH, socioeconomic status, clinical characteristics, sub-regional divisions, comorbidities, treatments, and metabolic controls, were evaluated using survey logistic regression. Findings The weighted prevalence rates (95% CI) of CKD, albuminuria, and decreased eGFR were 32.6% (31.3%- 33.8%), 30.8% (29.6%-32.1%), and 5.5% (5.1%-5.9%), respectively. Among those with CKD, 25.7% had diabetic retinopathy (DR) and 22.3% had cardiovascular disease (CVD). The weighted prevalence rates of albuminuria and decreased eGFR were consistently higher among southern residents, rural residents, and individuals with more severe DR and a history of CVD than their counterparts (all p < 0.05). After adjustment for age, sex, sub-regional division, setting, educational level, annual household income, family history of diabetes, diabetes duration, glucose-lowering treatment, any DR, CVD, and drinking status, the logistic models showed that the odds ratios (ORs) (95% CI) for albuminuria and decreased eGFR were 0.46 (0.42-0.51) and 0.61 (0.55-0.67) for the participants with moderate scores, and 0.14 (0.10-0.21) and 0.28 (0.19-0.41) for those with high scores, compared with those with low total LE8 scores. Furthermore, the restricted cubic spline curves depicted that the disparities in the odds of having albuminuria or decreased eGFR among subpopulations grouped by sex, age, setting, and geographical region, significantly decreased and even disappeared in some cases as the LE8 scores increased. Interpretation Chinese adults with diabetes are heavily burdened by CKD. Optimized CVH is central to reducing CKD risk across different subpopulations. Funding National Key Clinical Specialty, the Chinese Academy of Engineering. Copyright (c) 2025 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Diabetic peripheral neuropathic pain (DPNP) is becoming increasingly prevalent as the global burden of diabetes continues to rise. DPNP manifests moderate-to-severe pain with burning, shooting, and tingling sensations, which increase clinical and economic burden and reduce the quality of life (QoL). α2δ ligands were developed on the basis of their mechanism of action involving the modulation of voltage-gated calcium channels (VGCCs). These ligands bind to the α2δ subunit of VGCCs, which reduces calcium influx and subsequently decreases the release of excitatory neurotransmitters. A majority of the clinical trials have demonstrated the efficacy of α2δ ligands in providing pain relief and improvement in the QoL for patients with DPNP. Furthermore, α2δ ligands have a tolerable safety profile, with somnolence and dizziness being the most frequently reported adverse events. Currently, most guidelines recommend calcium channel α2δ ligands as first-line treatment for DPNP. With the development of drug research, mirogabalin, an emerging novel α2δ ligand, was developed and validated. This review aims to summarize the latest status of α2δ ligand development and provide a comprehensive evaluation of α2δ ligands for the management of DPNP, emphasizing the potential mechanism of action, clinical efficacy, safety profile, and pharmacoeconomics. Further perspectives are warranted for treatment strategies to address individual patient care. A Graphical Abstract is availible for this article.

This study aims to evaluate the efficacy and safety of Crisugabalin in patients with diabetic peripheral neuropathic pain (DPNP), with a focus on its rapid onset of action. All the analyses in this study were based on data from a phase 2/3 adaptive randomized clinical trial that enrolled 596 patients. Participants were categorized into four treatment groups according to the intervention received: Crisugabalin 40 mg/day, Crisugabalin 80 mg/day, placebo, and Pregabalin 300 mg/day. The primary endpoint was the change in the average daily pain score (ADPS) over a 13-week treatment period. Secondary endpoints included changes in the Numeric Rating Scale (NRS) and the daily sleep interference score (DSIS) during the first two weeks of treatment. Both Crisugabalin treatment groups (40 mg/day and 80 mg/day) demonstrated statistically significant reductions in ADPS compared to the placebo group starting from week 1 and continuing through week 13 (P < 0.05). Significant differences in pain relief for the Pregabalin group were observed only from week 6. Improvements in NRS and DSIS scores were also noted in both Crisugabalin groups, with statistically significant enhancements evident as early as day 2 of administration. Safety assessments indicated that Crisugabalin was well-tolerated, with a low incidence of serious adverse events and no significant increase in dropout rates among participants. The findings suggest that Crisugabalin offers effective pain relief with an acceptable safety profile, highlighting its rapid onset in patients with DPNP. Clinical trial registration number derived from our parent project, we have retained the original registration identifier: NCT04647773.

AIM:Fotagliptin is a novel dipeptidyl peptidase-4 inhibitor for glycaemic control in patients with type 2 diabetes (T2D). This trial aimed to assess the efficacy and safety of fotagliptin add-on to metformin in patients with T2D. MATERIALS AND METHODS:In this phase 3 randomised, double-blind, placebo-controlled study, patients with T2D who had inadequate glycaemic control using metformin alone were randomly allocated to fotagliptin or placebo at a 2:1 ratio for 24-week double-blind treatment period, followed by an open-label treatment with fotagliptin for all patients, making up a total of 52 weeks. All eligible patients were treated with a stable dose of metformin (≥1500 mg per day). The primary endpoint was the change in HbA1c level from baseline to week 24. Safety was assessed in all patients who received at least one dose of the study drug. RESULTS:After 24 weeks, LS mean change of HbA1c from baseline was -0.81% with fotagliptin versus -0.28% with placebo. Estimated treatment difference for fotagliptin versus placebo of HbA1c was -0.53% (95% confidence interval [CI] -0.68% to -0.39%; p < 0.001). Significantly more patients on fotagliptin than on placebo achieved HbA1c < 7.0% after 24 weeks (38.7% vs. 16.9%; p < 0.001). The incidence of adverse events was similar between the two groups. No severe hypoglycaemia events were reported in patients treated with fotagliptin and metformin combined therapy. CONCLUSIONS:In patients with T2D who experienced inadequate glycaemic control with metformin, fotagliptin achieved a superior and clinically meaningful improvement in glycaemic control compared with placebo.

Background:Intermittent fasting (IF) and glucagon-like peptide-1 receptor agonists (GLP-1RA) offer effective therapeutic options for nonalcoholic fatty liver disease (NAFLD). This study aimed to examine the effects of alternate-day fasting (ADF) alone and with liraglutide, and to explore the mechanisms behind each treatment. Methods:To establish the model for NAFLD, Sprague-Dawley rats were given a high-fat diet for 25 weeks. Subsequently, the rats were assigned to the ADF, ADF combined with liraglutide (A+L), and control groups for an additional 5 weeks. Evaluations were performed on liver morphology, body weight, serum lipid profiles, insulin sensitivity, and liver proteomics. Results:Compared to the control group, ADF alone demonstrated a reduction in body weight (37.1±15.56 g vs -20.68±15.58 g, p<0.05), food intake (0.30±0.002 g/d/rat vs 0.18±6.21 g/d/rat), blood lipid levels, and ALT concentration (139.0±15.57 U/L vs 91.25±41.9 U/L, p<0.05), while also improving the NAFLD score. Furthermore, ADF in conjunction with liraglutide exhibited superior effects in reducing body weight (-96.15±15.78 g), food intake (-10.25±0.01 g/d/rat), triglyceride (17.53±0.25 nmol/L), and LDL concentrations (6.93±0.35mmol/L), as well as ameliorating insulin resistance and lowering the NAFLD score relative to the ADF group (p<0.05). The proteomic analysis indicates that G protein-coupled receptor 39 (GPR39) and transmembrane protein 41b (Tmem41b) were significantly upregulated in the A+L group compared to the other two groups. Additionally, hydroxysteroid 17β-dehydrogenase 2 (HSD17B2) was significantly diminished in both the ADF and A+L groups relative to the control group. Conclusion:Intermittent fasting, in conjunction with GLP-1RA, further enhances metabolic health in individuals with NAFLD as a result of obesity. This study provides support for forthcoming clinical trials and aims to establish new therapeutic targets in the context of NAFLD.

ImportanceMany patients with diabetic peripheral neuropathic pain (DPNP) experience inadequate relief, despite best available medical treatments. There are no approved and effective therapies for patients with DPNP in China.ObjectiveTo evaluate the efficacy and safety of capsules containing γ-aminobutyric acid (GABA) analogue HSK16149 in the treatment of Chinese patients with DPNP.Design, Setting, and ParticipantsThis phase 2 to 3 adaptive randomized clinical trial was multicenter, double blind, and placebo and pregabalin controlled. The trial started on December 10, 2020, and concluded on July 8, 2022. In stage 1, various doses of HSK16149 were evaluated to determine safety and efficacy for stage 2. The second stage then validated the efficacy and safety of the recommended dose.InterventionIn stage 1, enrolled patients (n = 363) were randomized 1:1:1:1:1:1 to 4 HSK16149 doses (40, 80, 120, or 160 mg/d), pregabalin (300 mg/d), or placebo. In stage 2, patients (n = 362) were randomized 1:1:1 to receive HSK16149, 40 or 80 mg/d, or placebo. The final efficacy and safety analysis pooled data from patients receiving the same treatment.Main Outcomes and MeasuresThe primary efficacy end point in stage 1 was the change from baseline in average daily pain score (ADPS) at week 5. The primary efficacy end point in stage 2 was the change from baseline in ADPS at week 13. When the final statistical analysis was performed, the P values calculated from the independent data of each phase were combined using the weighted inverse normal method to make statistical inferences.ResultsOf 725 randomized patients in the full-analysis set (393 men [54.2%]; mean [SD] age, 58.80 [9.53] years; 700 [96.6%] of Han Chinese ethnicity), 177 received placebo; 178, HSK16149, 40 mg/d; 179, HSK16149, 80 mg/d; 66, HSK16149, 120 mg/d; 63, HSK16149, 160 mg/d; and 62, pregabalin, 300 mg/d. A total of 644 patients (88.8%) completed the study. The 40- and 80-mg/d doses of HSK16149 were recommended in stage 2. At week 13, the ADPS mean (SD) change from baseline was −2.24 (1.55) for the 40-mg/d and −2.16 (1.79) for 80-mg/d groups and −1.23 (1.68) for the placebo group, showing statistical significance for both HSK16149 doses vs placebo (both P < .001). In a safety set (n = 726), 545 patients (75.1%) had adverse events, which were generally mild to moderate, with dizziness and somnolence being the most common.Conclusions and RelevanceForty- and eighty-mg/d doses of HSK16149 were recommended for treating patients with DPNP in China. The efficacy of HSK16149 capsules was superior to placebo in all groups for relieving DPNP and appeared well tolerated.Trial RegistrationClinicalTrials.gov Identifier: NCT04647773

AIM:To evaluate the effect of age and disease duration on the efficacy and safety of iGlarLixi versus insulin glargine 100 units/ml (iGlar) or lixisenatide (Lixi) alone in Asian people with type 2 diabetes (T2D) uncontrolled on oral antidiabetic drugs (LixiLan-O-AP) or basal insulin ± oral antidiabetic drugs (LixiLan-L-CN). MATERIALS AND METHODS:In this post hoc analysis, the glycated haemoglobin (HbA1c) changes were assessed from baseline to week 24 (LixiLan-O-AP) or 30 (LixiLan-L-CN) in subgroups defined by baseline age (<65, ≥65 years) and duration of T2D. The proportion who achieved the composite of HbA1c <7% (<53.0 mmol/mol) without weight gain and without symptomatic hypoglycaemia (plasma glucose ≤3.9 mmol/L) and the incidences of hypoglycaemia and gastrointestinal disorders were also analysed. RESULTS:HbA1c reductions were consistently greater with iGlarLixi versus iGlar or Lixi across all subgroups, including participants aged ≥65 years and those with T2D for ≥15 or ≥20 years. Greater proportions of participants achieved HbA1c <7% (<53.0 mmol/mol) without weight gain or hypoglycaemia with iGlarLixi versus iGlar or Lixi, regardless of age or T2D duration. Hypoglycaemia incidence was similar with iGlarLixi versus iGlar across most subgroups; the incidence of gastrointestinal disorders was lower with iGlarLixi versus Lixi in all subgroups. CONCLUSIONS:iGlarLixi showed consistent efficacy and safety across all age and disease duration subgroups in Asian people with uncontrolled T2D, including older individuals and those with longstanding disease.

AIM:This trial assessed the efficacy and safety of 2.24 g intragastric expandable capsules twice per day versus placebo for weight management in adults with overweight or obesity. METHODS:This double-blind, placebo-controlled study included adults with a body mass index of at least 24 kg/m2 and no more than 40 kg/m2 . In total, 280 participants were recruited from six hospitals in China and were assigned in a 1:1 ratio to receive 2.24 g oral intragastric expandable capsules or placebo for 24 weeks. Coprimary endpoints were the percentage change in body weight from baseline and the rate of weight reduction of ≥5%, assessed using both the full analysis set and per protocol set. RESULTS:At baseline, the mean body weight was 81.8 kg, and the mean body mass index was 29.4 kg/m2 . The mean body weight change at week 24 was -4.9% with intragastric expandable capsules versus -1.9% with placebo [estimated treatment difference (ETD) -3.0%, 95% confidence interval (CI) -4.1 to -1.9; p < .001] using the full analysis set and -6.1% versus -2.5% (ETD -3.6%, 95% CI -5.0 to -2.3; p < .001), respectively, using the per protocol set. The percentage of participants who had weight loss exceeding 5% was 45.0% in the intragastric expandable capsule group versus 19.7% in the placebo group (ETD 25.3%, 95% CI 14.7-35.9; p < .001) in the full analysis set and 55.9% versus 26.2% (ETD 29.6%, 95% CI 17.1-42.2; p < .001), respectively, in the per protocol set. Waist circumference significantly decreased at week 24 (intragastric expandable capsules vs. placebo: -5.6 ± 8.3 cm vs. -2.9 ± 4.8 cm; p = .003). The most common adverse events associated with the use of intragastric expandable capsules were gastrointestinal disorders (intragastric expandable capsule vs. placebo, 25.0% vs. 21.9%), and most were mild and transient. CONCLUSIONS:In this 24-week trial including participants with overweight or obesity, 2.24 g of intragastric expandable capsules twice daily led to a clinically meaningful reduction in body weight compared with placebo.

Background Our study aimed to investigate the prevalence and demographic characteristics of immune checkpoint inhibitor-associated hypophysitis (ICI-hypophysitis) using data from the FAERS, and the risk factors of prognosis were explored. Methods In this retrospective study, all cases of newly-diagnosed hypophysitis associated with FDA approved ICIs from 1st January 2007 to 31st December 2022 were accumulated using FAERS. Demographic data including age, sex, body weight, the prognosis of cases, and other co-occurred endocrinopathies induced by ICIs were analyzed and compared between different subgroups of immunotherapy. Results The reporting frequency of ICI-hypophysitis was 1.46% (2343/160089). Patients on the combination therapy had higher risk of hypophysitis reporting, followed by anti-CTLA-4 agent compared with other monotherapies (p < 0.001). Male subjects displayed higher reporting risk of ICI-hypophysitis (p = 0.015). Patients on anti-PD-1 therapy or the combination therapy showed higher occurrence rate of type 1 diabetes (anti-PD-1 vs. anti-PD-L1 vs. anti-CTLA-4 vs. combination therapy, 4.2% vs. 0.7% vs. 0.3% vs. 8.4%, p < 0.001). The occurrence rate of new-onset thyroid diseases in patients receiving combination therapy was higher than anti-PD-1 monotherapy (12.3% vs. 8.4%, p = 0.010). Elder age, lung cancer, and renal cancer emerged to be positively associated with severe clinical outcomes [>65 years, OR 1.042, 95%CI (1.022-1.063), p < 0.001; lung cancer, OR 1.400, 95%CI (1.019-1.923), p = 0.038; renal cancer, OR 1.667, 95%CI (1.153-2.412), p = 0.007]. Anti-CTLA-4 monotherapy was discovered to be a protective factor of severe outcomes [OR 0.433, 95%CI (0.335-0.558), p < 0.001]. Female sex and co-occurrence of ICI-related diabetes exhibited lower risk of death [female, OR 0.571, 95%CI (0.361-0.903), p = 0.017; diabetes, OR 0.090, 95%CI (0.016-0.524), p = 0.007]. Conclusions ICI-induced hypophysitis is male-predominant irAE, most commonly seen in patients on anti-CTLA-4 mono- or combination therapy. Awareness among clinicians is critical when patients with elder age, lung or renal cancer develop hypophysitis, which indicates poor clinical outcomes. Female sex, anti-CTLA-4 monotherapy and co-occurrence of ICI-related diabetes are protective risk factors for poor prognosis.

Introduction & Objective: Chronic diabetic peripheral neuropathic pain (DPNP) exerts serious adverse effects on patients' emotions and quality of life. Crisugabalin has shown favorable efficacy and safety in a phase II/III study in Chinese patients with DPNP. In this open-label extension study, we further evaluated the long-term safety and efficacy of Crisugabalin Besilate. Methods: A total of 301 patients with DPNP from the previous phase II/III trial were enrolled in this 52-week open-label study. Patients received Crisugabalin Besilate capsule 40mg twice daily. Pain intensity was measured with Short-Form McGill Pain Questionnaire (SF-MPQ), including Pain Rating Index (PRI), Visual Analogue Scale (VAS), and Present Pain Intensity (PPI). Results: All the efficacy indicators of SF-MPQ showed continuous decrease throughout the trial, and the scores at week 52 were significantly different compared with baseline. The mean changes in PRI and VAS from baseline at week 52 were -2.5±3.97 and -23.4±19.38, respectively, and that the proportion of subjects with PPI ≤ 1 increased by 19% from baseline. 86.4% subjects experienced a total of 1095 Treatment Emergent Adverse Events (TEAEs) during the study, including 203 drug-related TEAEs with the incidence of 38.9%. The most common drug-related TEAEs were dizziness (27.2%) and somnolence (8.3%), and the majority were mild to moderate. The incidence of TEAEs leading to dose reduction was 14.3%. Conclusions: Long-term treatment with Crisugabalin Besilate is effective and safe for pain relief in Chinese patients with DPNP. Disclosure T. Zhang: None. X. Guo: None. H. Li: None. J. Ma: None. L. Yukun: None. C. Jiang: None. J. Liu: None. Funding Haisco Pharmaceutical Group, Sichuan, China

BackgroundLarge-scale prospective cohort studies on diabetic foot ulcers risk factor screening in China are limited. Therefore, this prospective cohort study aimed to explore the predictive risk factors for diabetic foot ulcers to provide clinicians with concise and effective clinical indicators for identifying a high-risk diabetic foot and guiding the prevention of diabetic foot ulcers.MethodsPatients with diabetes who visited the Department of Endocrinology of Peking University First Hospital from October 2017 to December 2018 were selected as research participants by convenience sampling. A total of 968 patients were included. After enrollment, a dedicated person collected and recorded all baseline data. A dedicated telephone follow-up was conducted every 12–24 months to evaluate whether the endpoint event had occurred. All patients were followed up for an average of 61 (57–71) months, with 95% of them followed up for more than 60 months. According to the occurrence of endpoint events, they were divided into the DFU and non-DFU groups. The data between the two groups were analyzed using independent-sample t-test, Wilcoxon rank sum test, and chi square test. We used univariate and multivariate logistic regression analysis to analyze the factors that affected the occurrence of diabetic foot ulcers.Results and conclusionsAfter the 5-year follow-up, the incidence of diabetic foot was 25.83%. Multivariate logistic regression analysis revealed that body mass index (odds ratio: 1.046; 95% confidence interval: 1.001–1.093), abnormal pinprick sensation (odds ratio: 4.138; 95% confidence interval: 1.292–13.255), history of fungal foot infection (odds ratio: 2.287; 95% confidence interval: 1.517–3.448), abnormal 128-Hz tuning fork test (odds ratio: 2.628; 95% confidence interval: 1.098–6.294), and HbA1c≥ 8% (odds ratio: 1.522; 95% confidence interval: 1.014–2.284) were independent predictors of diabetic foot. Our study highlights clinically relevant indicators that may help to prevent the occurrence of diabetic foot and guide timely interventions.

Aim: This study aimed to assess the efficacy and safety of prusogliptin (DBPR108), a novel and highly selective dipeptidyl peptidase-4 inhibitor, in individuals with type 2 diabetes who had not been using glucose-lowering agents regularly for the 8 weeks before the screening period.Materials and Methods: In this multicentre, randomized, double-blind, phase 3 study, adult patients with type 2 diabetes were randomly assigned to receive either DBPR108 100 mg, sitagliptin 100 mg, or placebo once daily during the initial 24-week double-blind treatment period, followed by a 28-week open-label extension period during which all patients received DBPR108 100 mg once daily. The primary endpoint was the mean change in glycated haemoglobin (HbA1c) levels from baseline to week 24.Results: In total, 766 patients were enrolled and received DBPR108 100 mg (n = 462), sitagliptin 100 mg (n = 152), or placebo (n = 152). The mean age of all patients was 54.3 +/- 10.5 years, with 58% being men. The median duration of type 2 diabetes was 0.38 (0.02, 2.65) years, and the mean HbA1c (SD) at baseline was 7.94% (0.62), 7.88% (0.61) and 7.83% (0.59) for DBPR108, sitagliptin and placebo groups, respectively. At week 24, the least square mean (SE) changes from baseline in HbA1c were -0.63% (0.04%) for DBPR108, -0.60% (0.07%) for sitagliptin and -0.02% (0.07%) for placebo. The mean treatment difference between DBPR108 and placebo was -0.61% (95% CI -0.77% to -0.44%), and between DBPR108 and sitagliptin was -0.03% (95% CI -0.19% to 0.13%). These results indicate that DBPR108 was superior to placebo and non-inferior to sitagliptin. DBPR108 also significantly reduced fasting and postprandial plasma glucose levels and had little effect on body weight. The mean (SD) changes in HbA1c from baseline to week 52 were -0.50% (0.97%) for the DBPR108 group, -0.46% (0.96%) for the sitagliptin group and -0.41% (0.95%) for the placebo group. The incidence of adverse events was comparable across all three groups.Conclusions: DBPR108 showed superiority to placebo and non-inferiority to sitagliptin in terms of glycaemic control over the initial 24 weeks in treatment-naive patients with type 2 diabetes. Furthermore, its efficacy was sustained for up to 52 weeks.

Importance Many patients with diabetic peripheral neuropathic pain (DPNP) experience inadequate relief, despite best available medical treatments. There are no approved and effective therapies for patients with DPNP in China. Objective To evaluate the efficacy and safety of capsules containing gamma-aminobutyric acid (GABA) analogue HSK16149 in the treatment of Chinese patients with DPNP. Design, Setting, and Participants This phase 2 to 3 adaptive randomized clinical trial was multicenter, double blind, and placebo and pregabalin controlled. The trial started on December 10, 2020, and concluded on July 8, 2022. In stage 1, various doses of HSK16149 were evaluated to determine safety and efficacy for stage 2. The second stage then validated the efficacy and safety of the recommended dose. Intervention In stage 1, enrolled patients (n = 363) were randomized 1:1:1:1:1:1 to 4 HSK16149 doses (40, 80, 120, or 160 mg/d), pregabalin (300 mg/d), or placebo. In stage 2, patients (n = 362) were randomized 1:1:1 to receive HSK16149, 40 or 80 mg/d, or placebo. The final efficacy and safety analysis pooled data from patients receiving the same treatment. Main Outcomes and Measures The primary efficacy end point in stage 1 was the change from baseline in average daily pain score (ADPS) at week 5. The primary efficacy end point in stage 2 was the change from baseline in ADPS at week 13. When the final statistical analysis was performed, the P values calculated from the independent data of each phase were combined using the weighted inverse normal method to make statistical inferences. Results Of 725 randomized patients in the full-analysis set (393 men [54.2%]; mean [SD] age, 58.80 [9.53] years; 700 [96.6%] of Han Chinese ethnicity), 177 received placebo; 178, HSK16149, 40 mg/d; 179, HSK16149, 80 mg/d; 66, HSK16149, 120 mg/d; 63, HSK16149, 160 mg/d; and 62, pregabalin, 300 mg/d. A total of 644 patients (88.8%) completed the study. The 40- and 80-mg/d doses of HSK16149 were recommended in stage 2. At week 13, the ADPS mean (SD) change from baseline was -2.24 (1.55) for the 40-mg/d and -2.16 (1.79) for 80-mg/d groups and -1.23 (1.68) for the placebo group, showing statistical significance for both HSK16149 doses vs placebo (both P < .001). In a safety set (n = 726), 545 patients (75.1%) had adverse events, which were generally mild to moderate, with dizziness and somnolence being the most common. Conclusions and Relevance Forty- and eighty-mg/d doses of HSK16149 were recommended for treating patients with DPNP in China. The efficacy of HSK16149 capsules was superior to placebo in all groups for relieving DPNP and appeared well tolerated.