Retrospective analysis of the effect of SGLT-2 inhibitors on renal function in patients with type 2 diabetes in the real world.

Introduction: The protective effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on the kidneys has been widely recognized. However, limited research has reported the changes in estimated glomerular filtration rate (eGFR) of real-world patients with type 2 diabetes mellitus (T2DM) over time after administration of SGLT-2 inhibitors. This study aimed to reflect the trend of eGFR changes over time in T2DM patients having different baseline eGFR after SGLT-2 inhibitors administration in the real world. Methods: A single-center retrospective study was performed in a tertiary public hospital in Beijing, China. In total, 998 outpatients with T2DM who initiated SGLT-2 inhibitors treatment were included in the study. The changes in eGFR, urinary albumin/creatinine ratio (UACR), and glycolipid metabolism indicators were analyzed during the 18-month follow-up period. Results: The eGFR levels significantly decreased to their lowest point (-3.04 mL/min/1.73 m2) in the first 3 months after initiation of SGLT-2 inhibitors treatment, however, gradually returned to the baseline level after 1 year. Compared to the subgroup with eGFR >90 mL/min/1.73 m2, improvements in renal function were more significant in patients with T2DM from the 60 < eGFR ≤90 mL/min/1.73 m2 and eGFR ≤60 mL/min/1.73 m2 subgroups after treatment with SGLT-2 inhibitors. Similarly, SGLT-2 inhibitors reduced the UACR in patients with diabetic nephropathy. Conclusion: This study further confirmed the real-world long-term protective effect of SGLT-2 inhibitors on the kidneys of patients with T2DM, which is not related to baseline renal function and blood glucose.

Consensus on glycemic management for patients with coronary heart disease and type 2 diabetes.

The prevalence of patients with coronary heart disease (CHD) and diabetes mellitus is notably high, posing significant residual cardiovascular risks even after routine interventions such as antihypertensive, lipid-lowering, and antithrombotic treatments. Recent studies have demonstrated that certain glucose-lowering medications confer cardiovascular benefits for patients with type 2 diabetes. However, a survey indicates that cardiologists may not be fully acquainted with the optimal screening timing, indicators, and diagnostic criteria for type 2 diabetes, and there is insufficient awareness and a low rate of prescription of novel glucose-lowering medications with proven cardiovascular efficacy, such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter-2 inhibitors (SGLT-2i). In this context, based on domestic and international guidelines or consensus and the latest evidence-based evidence, this consensus aims to standardize the glycemic management for patients with acute coronary syndrome, chronic coronary syndrome, and perioperative management for percutaneous coronary intervention. It highlights the key points of screening and diagnosis of type 2 diabetes, and the comprehensive management of cardiovascular risk in patients with CHD. The consensus elaborates on the principles and algorithms of glycemic management for CHD patients, without involving acute complications of diabetes, clarifies the clinical practice of glucose-lowering medications with cardiovascular benefits, and promotes the standardized use of these medications in cardiovascular and other related specialty fields. Additionally, it addresses the glucose-lowering treatment to comprehensively reduce cardiovascular risks.

Phenotypic features, prevalence of KCNJ11-MODY in Chinese patients with early-onset diabetes and a literature review.

OBJECTIVE: Gain-of-function (GOF) variants of KCNJ11 cause neonate diabetes and maturity-onset diabetes of the young (KCNJ11-MODY), while loss-of-function (LOF) variants lead to hyperinsulinemia hypoglycemia and subsequent diabetes. Given the limited research of KCNJ11-MODY, we aimed to analyse its phenotypic features and prevalence in Chinese patients with early-onset type 2 diabetes (EOD). DESIGN, PATIENTS AND MEASUREMENTS: We performed next-generation sequencing on 679 Chinese EOD patients to screen for KCNJ11 exons variants. Bioinformatics prediction and the American College of Medical Genetics and Genomics guidelines was used to determine the pathogenicity and diagnosed KCNJ11-MODY. A literature review was conducted to investigate the phenotypic features of KCNJ11-MODY. RESULTS: We identified six predicted deleterious rare variants in six EOD patients (0.88%). They were classified as uncertain significance (variant of uncertain significance [VUS]), but more common in this EOD cohort than a general Chinese population database, however, without significant difference (53/10,588, 0.50%) (p = .268). Among 80 previously reported patients with KCNJ11-MODY, 23.8% (19/80) carried 9 (32.1%) LOF variants, who had significantly older age at diagnosis, higher birthweight and higher fasting C-peptide compared to patients with GOF variants. Many patients carrying VUS were not correctly diagnosed. CONCLUSIONS: Some rare variants of KCNJ11 might contribute to the development of Chinese EOD, although available evidence has not enough power to support them as cause of KCNJ11-MODY. The clinical features of LOF variants were different from GOF variants in KCNJ11-MODY patients. It is necessary to evaluate the pathogenicity of VUS through function experiments.

Low C reactive protein-alleles in hepatocyte nuclear factor 1A are associated with an increased risk of cardiovascular disease: a Meta-analysis.

CONTEXT: Rare variants in HNF1A cause both maturity onset diabetes of the young 3 (HNF1A-MODY) and reduced serum C reactive protein (CRP) levels. Common variants of HNF1A are associated with serum CRP and type 2 diabetes, but inconsistently with cardiovascular disease (CVD). OBJECTIVE: Our study aimed to investigate the association of low CRP-alleles in HNF1A with CVD and indirectly evaluate the CVD risk of HNF1A-MODY patients because of unavailability of enough cases to study their clinical outcomes. DATA SOURCES: A literature search was performed using PubMed, Embase and Cochrane Library databases from inception to December 2023. STUDY SELECTION: All relevant studies concerning the association of HNF1A with CRP, CVD, lipid and type 2 diabetes were included. DATA EXTRACTION: Odds ratios (ORs), 95% confidence intervals (CIs) and study characteristics were extracted. DATA SYNTHESIS: Three common coding variants of HNF1A (rs1169288, rs2464196, rs1169289) were examined. The minor alleles of these variants correlated with low CRP levels (OR 0.89, 95%Cl 0.86-0.91; OR 0.89, 95%Cl 0.88-0.91; OR 0.89, 95%Cl 0.88-0.91, respectively). Their low CRP-alleles were associated with increased risk of CVD (OR 1.03, 95%CI 1.03-1.04), higher LDL-cholesterol levels (OR 1.07, 95%CI 1.04-1.10) and elevated risk of type 2 diabetes (OR 1.04, 95%CI 1.01-1.08). CONCLUSIONS: Our study revealed an association between low CRP-alleles in HNF1A and a high CVD risk, which indicated that anti-diabetic drugs with cardiovascular benefits such as GLP-1 receptor agonist should be recommended as first-line choice for HNF1A-MODY.

Perceptions, attitudes and barriers to effective obesity care among people living with obesity and healthcare professionals in China: The ACTION-China study.

AIMS: To identify perceptions, attitudes, behaviours and barriers to effective obesity care among people living with obesity (PLwO) and healthcare professionals (HCPs) across mainland China. MATERIALS AND METHODS: ACTION-China (ClinicalTrials.gov: NCT05428501) was a cross-sectional, observational, descriptive, online survey-based study of 7000 PLwO and 1000 HCPs (conducted between August and November 2022). RESULTS: The majority of PLwO (76.8% [5374/7000]) and HCPs (94.6% [946/1000]) agreed that obesity is a chronic disease. Only 40.8% of PLwO (2853/7000) had discussed their weight or talked about losing weight with an HCP in the past 5 years. The most frequent reason given by PLwO for not discussing weight management with an HCP was believing it was their responsibility to manage their weight (34.7% [2430/7000]), whereas the most frequent reason HCPs gave for not discussing obesity with their patients with obesity was having more important health issues to discuss (72.1% [721/1000]). A smaller proportion of PLwO (19.1%) than HCPs (53.6%) felt that weight management discussions with an HCP would be very or extremely helpful for the patient, and 30.7% of PLwO experienced negative feelings after their most recent discussion. Overall, 34.8% (2438/7000) of PLwO had been diagnosed with obesity by an HCP, while 30.0% (2101/7000) of PLwO did not recognize that they had obesity. CONCLUSIONS: This large, national survey conducted among PLwO and HCPs highlights key barriers to effective obesity care in China, including underestimation of weight status by PLwO and the need for increased communication between HCPs and PLwO regarding weight management.

ISIS 449884 Injection Add-On to Metformin in Patients with Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Phase II Clinical Study.

INTRODUCTION: ISIS 449884, a 2'-O-methoxyethyl antisense oligonucleotide that targets the glucagon receptor (GCGR), has demonstrated an ability to reduce hepatic glucose output and lower the blood glucose level. The primary objective of this study was to investigate the safety and efficacy of ISIS 449884 as an add-on to metformin in a population of Chinese patients with type 2 diabetes mellitus (T2DM). METHOD: This was a multicenter, placebo-controlled (2:1), randomized, double-blind, parallel-enrollment, multiple-dose phase II study in Chinese patients with T2DM. A total of 90 patients who were uncontrolled by stable metformin monotherapy were randomized into three cohorts. Thirty subjects were enrolled in each cohort and received injections of ISIS 449884 (50 mg or 60 mg weekly or 100 mg every other week) or a corresponding volume of placebo (0.25 mL and 0.3 mL weekly or 0.5 mL every other week) subcutaneously in a 2:1 ratio for 16 weeks. RESULTS: The primary efficacy endpoint was analyzed in 88 subjects (ISIS 449884, n = 59; placebo, n = 29). The corrected LS mean change from baseline in glycated hemoglobin (HbA1c) at week 17 in the pooled ISIS 449884 treatment group was - 1.31% (95% CI - 1.66%, - 0.96%), and that in the pooled placebo group was 0.15% (95% CI - 0.37%, 0.66%). The LS mean difference between the two groups was - 1.46% (95% CI - 1.92%, - 1.00%, P < 0.001). Treatment-emergent adverse events (TEAEs) occurred in 53/60 subjects (88.3%) and 25/30 subjects (83.3%) in the pooled ISIS 449884 treatment group and the pooled placebo group, respectively, with similar incidences. Drug-related TEAEs occurred in 41/60 subjects (68.3%) and 9/30 subjects (30.0%), respectively. TEAEs of grade 3 or higher occurred in 5/60 (8.3%) subjects and 2/30 (6.7%) subjects, respectively, and none of them were drug related. CONCLUSIONS: The ISIS 449884 injection add-on to metformin significantly reduced HbA1c in patients with T2DM uncontrolled by stable metformin monotherapy and showed an acceptable benefit/risk profile. CLINICAL TRIAL REGISTRATION: www.chinadrugtrials.org.cn , CTR20191096.

Efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes uncontrolled with metformin: PIONEER 12, a double-blind, Phase IIIa, randomised trial.

AIMS/HYPOTHESIS: The aim of this study was to assess the efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment. METHODS: The Peptide Innovation for Early Diabetes Treatment (PIONEER) 12 trial was a randomised, double-dummy, active-controlled, parallel-group, Phase IIIa trial conducted over 26 weeks at 90 sites across the China region (including mainland China, Taiwan and Hong Kong) and five other countries. Adults aged ≥18 years (≥20 years in Taiwan) with a diagnosis of type 2 diabetes, HbA1c between 53 and 91 mmol/mol (inclusive) and treated with a stable daily dose of metformin were eligible for inclusion. Participants were randomised (1:1:1:1) using a web-based randomisation system to either once-daily oral semaglutide (3 mg, 7 mg or 14 mg) or once-daily oral sitagliptin 100 mg. Treatment allocation was masked to both participants and investigators. Randomisation was stratified according to whether participants were from the China region or elsewhere. The primary endpoint was change in HbA1c from baseline to week 26. The confirmatory secondary endpoint was change in body weight (kg) from baseline to week 26. All randomised participants were included in the full analysis set (FAS). All participants exposed to at least one dose of trial product were included in the safety analysis (SAS). RESULTS: Of 1839 participants screened, 1441 were randomly assigned to oral semaglutide 3 mg (n=361), 7 mg (n=360), 14 mg (n=361) or sitagliptin 100 mg (n=359) and included in the FAS. A total of 1438 participants were included in the SAS. In total, 75.2% of participants were from the China region. A total of 1372 (95.2%) participants completed the trial and 130 participants prematurely discontinued treatment (8.3%, 8.6% and 15.0% for oral semaglutide 3 mg, 7 mg and 14 mg, respectively; 4.2% for sitagliptin 100 mg). Significantly greater reductions in HbA1c from baseline to week 26 were reported for all doses of oral semaglutide vs sitagliptin 100 mg. For oral semaglutide 3 mg, 7 mg and 14 mg vs sitagliptin 100 mg, the estimated treatment differences (ETDs [95% CI]) were -2 (-4, -1) mmol/mol, -8 (-9, -6) mmol/mol and -11 (-12, -9) mmol/mol, respectively. The corresponding ETDs (95% CI) in percentage points vs sitagliptin 100 mg were -0.2 (-0.3, -0.1), -0.7 (-0.8, -0.6) and -1.0 (-1.1, -0.8), respectively. Reductions in body weight were significantly greater for all doses of oral semaglutide vs sitagliptin 100 mg (ETD [95% CI] -0.9 [-1.4, -0.4] kg, -2.3 [-2.8, -1.8] kg and -3.3 [-3.8, -2.8] kg for 3 mg, 7 mg and 14 mg, respectively). In the subpopulation of participants from the China region (75.2% of trial participants), reductions in HbA1c and body weight from baseline to week 26 were similar to those seen in the overall population. The most frequent adverse events in the semaglutide treatment arms were gastrointestinal, although these were mostly transient and mild/moderate in severity. CONCLUSIONS/INTERPRETATION: Significantly greater reductions in both HbA1c and body weight over 26 weeks were seen with oral semaglutide 3 mg, 7 mg and 14 mg than with sitagliptin 100 mg in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment. Oral semaglutide was generally well tolerated, with a safety profile consistent with that seen in the global PIONEER trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT04017832. FUNDING: This trial was funded by Novo Nordisk A/S, Søborg, Denmark.

Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial.

People with type 2 diabetes and chronic kidney disease have a high risk for kidney failure and cardiovascular (CV) complications. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors (SGLT2i) independently reduce CV and kidney events. The effect of combining both is unclear. FLOW trial participants with type 2 diabetes and chronic kidney disease were stratified by baseline SGLT2i use (N = 550) or no use (N = 2,983) and randomized to semaglutide/placebo. The primary outcome was a composite of kidney failure, ≥50% estimated glomerular filtration rate reduction, kidney death or CV death. The risk of the primary outcome was 24% lower in all participants treated with semaglutide versus placebo (95% confidence interval: 34%, 12%). The primary outcome occurred in 41/277 (semaglutide) versus 38/273 (placebo) participants on SGLT2i at baseline (hazard ratio 1.07; 95% confidence interval: 0.69, 1.67; P = 0.755) and in 290/1,490 versus 372/1,493 participants not taking SGLT2i at baseline (hazard ratio 0.73; 0.63, 0.85; P < 0.001; P interaction 0.109). Three confirmatory secondary outcomes were predefined. Treatment differences favoring semaglutide for total estimated glomerular filtration rate slope (ml min-1/1.73 m2/year) were 0.75 (-0.01, 1.5) in the SGLT2i subgroup and 1.25 (0.91, 1.58) in the non-SGLT2i subgroup, P interaction 0.237. Semaglutide benefits on major CV events and all-cause death were similar regardless of SGLT2i use (P interaction 0.741 and 0.901, respectively). The benefits of semaglutide in reducing kidney outcomes were consistent in participants with/without baseline SGLT2i use; power was limited to detect smaller but clinically relevant effects. ClinicalTrials.gov identifier: NCT03819153 .

Real-world effectiveness of early insulin therapy on the incidence of cardiovascular events in newly diagnosed type 2 diabetes.

Early insulin therapy is capable to achieve glycemic control and restore ß-cell function in newly diagnosed type 2 diabetes (T2D), but its effect on cardiovascular outcomes in these patients remains unclear. In this nationwide real-world study, we analyzed electronic health record data from 19 medical centers across China between 1 January 2000, and 26 May 2022. We included 5424 eligible patients (mean age 56 years, 2176 women/3248 men) who were diagnosed T2D within six months and did not have prior cardiovascular disease. Multivariable Cox regression models were used to estimate the associations of early insulin therapy (defined as the first-line therapy for at least two weeks in newly diagnosed T2D patients) with the incidence of major cardiovascular events including coronary heart disease (CHD), stroke, and hospitalization for heart failure (HF). During 17,158 persons years of observation, we documented 834 incident CHD cases, 719 stroke cases, and 230 hospitalized cases for HF. Newly diagnosed T2D patients who received early insulin therapy, compared with those who did not receive such treatment, had 31% lower risk of incident stroke, and 28% lower risk of hospitalization for HF. No significant difference in the risk of CHD was observed. We found similar results when repeating the aforesaid analysis in a propensity-score matched population of 4578 patients and with inverse probability of treatment weighting models. These findings suggest that early insulin therapy in newly diagnosed T2D may have cardiovascular benefits by reducing the risk of incident stroke and hospitalization for HF.

Characterization of tirzepatide-treated patients achieving different glycemic control levels in SURPASS-AP-Combo.

OBJECTIVE: The study objective was to characterize subgroups of Asia-Pacific patients with type 2 diabetes who achieved different glycated hemoglobin (HbA1c) targets on tirzepatide treatment. METHODS: This was a post hoc analysis of the SURPASS AP-Combo study. Baseline characteristics, changes in metabolic markers, and safety were compared between tirzepatide-treated patients achieving HbA1c <7.0% (<53 mmol/mol) and those achieving ≥7.0% (≥53 mmol/mol) at week 40. Among patients achieving HbA1c <7.0% (<53 mmol/mol), further comparisons were conducted among subgroups achieving HbA1c <5.7% (<39 mmol/mol), 5.7% to 6.5% (39 to 48 mmol/mol), and >6.5% to <7.0% (>48 to <53 mmol/mol). RESULTS: Five hundred ninety-eight patients on tirzepatide treatment without rescue medication were included (56.9% male; mean age: 53.1 years; mean baseline HbA1c: 8.7% [71.6 mmol/mol]). Patients achieving HbA1c <7.0% (<53 mmol/mol) versus ≥7.0% (≥53 mmol/mol) were slightly younger with a shorter disease duration and lower HbA1c at baseline, and they had greater improvements in HbA1c, fasting serum glucose, body weight, BMI, waist circumference, waist-height ratio, diastolic blood pressure, lipids, and self-monitored blood glucose at week 40. Patients achieving HbA1c <5.7% (<39 mmol/mol) versus those achieving 5.7% to 6.5% (39 to 48 mmol/mol) and those achieving >6.5% to <7.0% (>48 to <53 mmol/mol) were much younger, had much lower HbA1c, and had further improvements in metabolic markers. Tirzepatide treatment was well tolerated irrespective of the HbA1c level achieved, with a low incidence of hypoglycemic events. CONCLUSIONS: These findings may help to inform clinical decisions in Asia-Pacific patients with type 2 diabetes.

Hypoglycemic Response to Dorzagliatin in a Patient With GCK-MODY.

OBJECTIVE: Metformin, insulin, and insulin secretagogues do not alter HbA1c levels in glucokinase maturity-onset diabetes of the young (GCK-MODY). However, the efficacy of the new hypoglycemic drugs on GCK-MODY remains unclear. RESEARCH DESIGN AND METHODS: We describe a case of GCK-MODY with unchanged blood glucose under different therapies during an 8 years' follow-up. His HbA1c and biochemical indices under different hypoglycemic treatments were recorded. RESULTS: Oral glucose-lowering drugs, including thiazolidinediones, dipeptidyl peptidase 4 inhibitor, α-glucosidase inhibitor, and sodium-glucose cotransporter 2 inhibitor that had not been evaluated previously, did not improve the HbA1c level in this patient. However, the glucokinase activator dorzagliatin effectively and safely lowered his HbA1c level. CONCLUSIONS: Dorzagliatin was effective and safe in this patient with GCK-MODY, providing potential application prospects for precise treatment of GCK-MODY with dorzagliatin.

Predictive value of postprandial C-peptide for utilizing multiple daily injection therapy in type 2 diabetes.

PURPOSE: Multiple daily injection (MDI) insulin therapy is an effective method of glycemic control and appropriate assignment to MDI therapy could minimize the risks of hypoglycemia and weight gain. The aim of the present study was to identify factors associated with indication for MDI therapy in type 2 diabetes (T2DM). METHODS: We recruited 360 participants with T2DM that were admitted to the Endocrinology Department of Peking University People's Hospital between August 2017 and July 2018. They first underwent intensive insulin therapy, then were switched to an optimized, simpler insulin treatment that aimed to maintain fasting blood glucose between 4.4 and 7.2 mmol/L, without episodes of hypoglycemia. The baseline characteristics of groups administering either MDI or basal/premix insulin were compared and multivariable logistic regression analysis was used to determine the odds ratios (ORs) for factors associated with MDI therapy. Receiver operating characteristic (ROC) curves were then used to identify independent predictors of MDI insulin regimen efficacy. RESULTS: The mean age of the participants was 57.6 ± 12.9 years, and diabetes duration was 14.2 ± 8.2 years. Two hundred and sixty-seven participants administered basal/premix insulin and 93 underwent MDI therapy, of whom 61.8% and 46.2% were male, respectively (p = 0.01). The duration of diabetes was significantly longer in the MDI group (13.1 ± 7.7 years vs. 17.3 ± 8.7 years; p < 0.01). Fasting plasma glucose (FPG) was higher in the MDI group than in the basal/premix group (8.3 [6.7, 11.3] mmol/L vs. 7.2 [5.7, 9.3] mmol/L; p < 0.01), while the postprandial C-peptide concentration (PCP) was significantly lower in the MDI group (2.6 [1.8, 3.5] ng/mL) compared to the basal/premix group (3.6 [2.5, 6.2] ng/mL, p < 0.01. Multivariable logistic regression analysis suggested that diabetes duration and FPG were positively associated with MDI therapy: OR (95% confidence interval [CI]) 1.06 (1.02, 1.10) and 1.12 (1.02, 1.24), respectively. In addition, PCP was negatively associated with MDI therapy (0.72 [0.60, 0.86]). ROC analysis suggested that a PCP of < 3.1 ng/mL predicted MDI therapy with 59.6% sensitivity and 72.1% specificity. CONCLUSION: The results of our study suggest that longer diabetes duration, higher FPG, and lower PCP were associated with necessity for MDI insulin regimen. These findings should assist with the personalization of insulin treatment.

Maximizing the Value of Real-World Data and Real-World Evidence to Accelerate Healthcare Transformation in China: Summary of External Advisory Committee Meetings.

Use of real-world data (RWD) is gaining wide attention. To bridge the gap between diverse healthcare stakeholders and to leverage the impact of Chinese real-world evidence (RWE) globally, a multi-stakeholder External Advisory Committee (EAC) and EAC meetings were initiated, aiming to elucidate the current and evolving RWD landscape in China, articulate the values of RWE in ensuring Chinese patients' equitable access to affordable medicines and solutions, and identify strategic opportunities and partnerships for expansion of RWE generation in China. Chinese and international experts who are clinicians and academic researchers were selected as EAC members based on their professional background and familiarity with RWD/RWE. Three EAC meetings were held quarterly in 2023. Various topics were presented and discussed for insights and suggestions. Nine experts from China, one from South Korea, and two from Europe were selected as EAC members and attended these meetings. Experts' presentations were summarized by theme, including the RWD landscape and RWE enablement in China, as well as global development of a patient-centric ecosystem. Experts' insights and suggestions on maximizing the RWD/RWE value to accelerate healthcare transformation in China were collected. We concluded that though data access, sharing, and quality are still challenging, RWD is developing to support evidence generation in the medicinal product lifecycle, inform clinical practice, and empower patient management in China. RWD/RWE creates value, accelerates healthcare transformation, and improves patient outcomes. Fostering a patient-centric ecosystem across healthcare stakeholders and maintaining global partnerships and collaboration are essential for unlocking the power of RWD/RWE.

Disparities in prevalence and treatment of diabetes, cardiovascular and chronic kidney diseases - Recommendations from the taskforce of the guideline workshop.

There is a mounting clinical, psychosocial, and socioeconomic burden worldwide as the prevalence of diabetes, cardiovascular disease (CVD), and chronic kidney disease (CKD) continues to rise. Despite the introduction of therapeutic interventions with demonstrated efficacy to prevent the development or progression of these common chronic diseases, many individuals have limited access to these innovations due to their race/ethnicity, and/or socioeconomic status (SES). However, practical guidance to providers and healthcare systems for addressing these disparities is often lacking. In this article, we review the prevalence and impact of healthcare disparities derived from the above-mentioned chronic conditions and present broad-based recommendations for improving access to quality care and health outcomes within the most vulnerable populations.

The opportunities and challenges of the disease-modifying immunotherapy for type 1 diabetes: A systematic review and meta-analysis.

There are multiple disease-modifying immunotherapies showing the potential of preventing or delaying the progression of type 1 diabetes (T1D). We designed and performed this systematic review and meta-analysis to gain an overview of what a role immunotherapy plays in the treatment of T1D. We searched PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to December 2023. We included clinical trials of immunotherapy conducted in patients with T1D that reported the incidence of hypoglycemia or changes from baseline in at least one of following outcomes: 2 h and 4 h mixed-meal-stimulated C-peptide area under the curve (AUC), fasting C-peptide, daily insulin dosage, glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG). The results were computed as the weighted mean differences (WMDs) or odds ratios (ORs) and 95% confidence intervals (CIs) in random-effect model. In all, 34 clinical trials were included. When compared with control groups, 2 h C-peptide AUC was marginally higher in patient treated with nonantigen-based immunotherapies (WMD, 0.04nmol/L, 95% CI, 0.00-0.09 nmol/L, P=0.05), which was mainly driven by the effects of T cell-targeted therapy. A greater preservation in 4 h C-peptide AUC was observed in patients with nonantigen-based immunotherapies (WMD, 0.10nmol/L, 95% CI, 0.04-0.16 nmol/L, P=0.0007), which was mainly driven by the effects of tumor necrosis factor α (TNF-α) inhibitor and T cell-targeted therapy. After excluding small-sample trials, less daily insulin dosage was observed in patient treated with nonantigen-based immunotherapies when compared with control groups (WMD, -0.07units/kg/day, 95% CI, -0.11 to -0.03units/kg/day, P=0.0004). The use of antigen-based immunotherapies was also associated with a lower daily insulin dosage versus control groups (WMD, -0.11units/kg/day, 95% CI, -0.23 to -0.00units/kg/day, P=0.05). However, changes of HbA1c or FPG were comparable between nonantigen-based immunotherapies or antigen-based immunotherapies and control groups. The risk of hypoglycemia was not increased in patients treated with nonantigen-based immunotherapies or patients treated with antigen-based immunotherapies when compared with control groups. In conclusion, nonantigen-based immunotherapies were associated with a preservation of 2 h and 4 h C-peptide AUC in patients with T1D when compared with the controls, which was mainly driven by the effects of TNF-a inhibitor and T cell-targeted therapy. Both nonantigen-based immunotherapies and antigen-based immunotherapies tended to reduce the daily insulin dosage in patients with T1D when compared with the controls. However, they did not contribute to a substantial improvement in HbA1c or FPG. Both nonantigen-based immunotherapies and antigen-based immunotherapies were well tolerated with not increased risk of hypoglycemia in patients with T1D.

Efficacy and Safety of Tirzepatide in Patients with Type 2 Diabetes: Analysis of SURPASS-AP-Combo by Different Subgroups.

INTRODUCTION: Tirzepatide is a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist. In the SURPASS-AP-Combo trial, once-weekly tirzepatide was associated with improved glycemic control and weight loss versus insulin glargine and was generally well tolerated in an Asia-Pacific, predominately Chinese, population with type 2 diabetes (T2D). This post hoc subgroup analysis of SURPASS-AP-Combo assessed the potential influence of patient baseline characteristics on the efficacy and safety of tirzepatide. METHODS: Changes from baseline to week 40 in HbA1c, body weight, fasting serum glucose (FSG), and daily glucose average from self-measured blood glucose profiles were analyzed by potential influential factors including age (< 65, ≥ 65 years), sex, baseline HbA1c (≤ 8.5, > 8.5%), body mass index (BMI) (< 25, ≥ 25 kg/m2), body weight (< 75, ≥ 75 kg), duration of diabetes (< 10, ≥ 10 years), and concomitant oral antihyperglycemic medications (metformin, metformin plus sulphonylurea). Gastrointestinal adverse events and hypoglycemia were also evaluated. RESULTS: At week 40, all tirzepatide doses were associated with reduced HbA1c, body weight, FSG, and daily glucose average from baseline in all subgroups. Greater HbA1c reductions were achieved in patients with higher baseline HbA1c across all tirzepatide doses, higher body weight with 10 mg and younger age with 15 mg tirzepatide. Greater reductions in body weight were observed in patients with higher body weight across all tirzepatide doses, lower baseline HbA1c with 5 mg and higher BMI with 5 mg tirzepatide. CONCLUSIONS: In this post hoc analysis, tirzepatide was associated with reduced blood glucose and body weight in a predominantly Chinese population with T2D across different subgroups, consistent with previous reports for tirzepatide. CLINICAL TRIAL REGISTRATION: NCT04093752.

CVOT Summit Report 2023: new cardiovascular, kidney, and metabolic outcomes.

The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD); advances in the management of type 1 diabetes (T1D) and its comorbidities; advances in the management of CKD with SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists (nsMRAs); and advances in the treatment of obesity with GLP-1 and dual GIP/GLP-1 receptor agonists. The association of diabetes and obesity with nonalcoholic steatohepatitis (NASH; metabolic dysfunction-associated steatohepatitis, MASH) and cancer and possible treatments for these complications were also explored. It is generally assumed that treatment of chronic diseases is equally effective for all patients. However, as discussed at the Summit, this assumption may not be true. Therefore, it is important to enroll patients from diverse racial and ethnic groups in clinical trials and to analyze patient-reported outcomes to assess treatment efficacy, and to develop innovative approaches to tailor medications to those who benefit most with minimal side effects. Other keys to a successful management of diabetes and comorbidities, including dementia, entail the use of continuous glucose monitoring (CGM) technology and the implementation of appropriate patient-physician communication strategies. The 10th Cardiovascular Outcome Trial Summit will be held virtually on December 5-6, 2024 ( http://www.cvot.org ).

Overburden of rare ALMS1 deleterious variants in Chinese early-onset type 2 diabetes with severe insulin resistance.

AIMS: Alström syndrome (AS) is a rare recessive disorder characterised by diabetes, obesity, insulin resistance (IR), and visual and hearing impairments. Mutations in the ALMS1 gene have been identified as the causative agents of AS. This study aimed to explore the relationship between rare ALMS1 variants and clinical features in Chinese patients with early-onset type 2 diabetes (age at diagnosis ≤40 years; EOD). MATERIALS AND METHODS: ALMS1 gene sequencing was performed in 611 Chinese individuals with EOD, 36 with postprandial hyperinsulinemia, and 47 with pre-diabetes and fasting IR. In-silico prediction algorithm and the American College of Medical Genetics Guidelines (ACMG) were used to evaluate the deleteriousness and pathogenicity of the variants. RESULTS: Sixty-two rare ALMS1 variants (frequency <0.005) were identified in 82 patients with EOD. Nineteen variants were predicted to be deleterious (pD). Patients with EOD carrying pD variants had higher fasting C-peptide, postprandial C-peptide, and HOMA2-IR levels than those without variants. The frequency of ALMS1 pD variants in the subgroup with more insulin-resistant EOD was higher than that in other EOD subgroups. Two patients with EOD, obesity, and IR who carried one heterozygous pathogenic/likely pathogenic rare variant of ALMS1 according to ACMG were identified. Moreover, rare heterozygous pD variants of ALMS1 were found in participants from cohorts of postprandial hyperinsulinemia as well as in pre-diabetes with fasting IR. CONCLUSIONS: ALMS1 rare pD variants are enriched in the populations with significant IR, which is a major hallmark of diabetes pathogenesis. Accordingly, our exploratory study provides insights and hypotheses for further studies of gene function.