Diabetes Therapy最新文献

Continuous glucose monitoring (CGM) has transformed diabetes management by providing continuous, high-resolution insight into glucose dynamics. Initially developed for type 1 diabetes, CGM now demonstrates substantial clinical and behavioral benefits for individuals with type 2 diabetes across diverse therapeutic settings. This narrative review synthesizes current evidence on the expanding role of CGM in optimizing glycemic control and promoting patient-driven lifestyle modification.Across randomized and real-world studies, CGM consistently improves glycosylated hemoglobin, increases time in range, and reduces glycemic variability, regardless of insulin use. Beyond metabolic outcomes, CGM enhances treatment satisfaction, psychological well-being, and self-efficacy, particularly when combined with structured education and feedback. By enabling individuals to visualize real-time glucose responses to daily behaviors, CGM serves as a powerful catalyst for sustained behavioral change and personalized self-management.In addition to its therapeutic applications, CGM also provides diagnostic insight by revealing unrecognized glucose excursions that conventional monitoring may miss, facilitating earlier identification of dysglycemia in at-risk individuals. Yet significant barriers persist, including device costs, limited insurance coverage, and the difficulty of translating raw data into actionable insights for patients and clinicians.In conclusion, CGM has evolved from a glucose-monitoring device to a comprehensive platform that supports both clinical decision-making and behavioral empowerment, bridging the continuum from diabetes prevention to long-term management.

Introduction: Type 2 diabetes is a leading cause of chronic kidney disease (CKD). Individuals with both conditions have increased risk of poor cardiorenal outcomes and mortality. The rapidly evolving landscape for CKD-protective therapies in type 2 diabetes currently includes sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA), both of which demonstrate cardiorenal outcome benefits. As part of the FOUNTAIN platform (ClinicalTrials.gov ID: NCT05526157; EUPAS ID: EUPAS48148), this study aimed to better understand changes in patient characteristics and treatment patterns corresponding with updates to clinical guideline recommendations and drug labeling and the emergence of new CKD-protective therapies such as finerenone in the US in 2021-2022.

Methods: An observational real-world data study assessed patient characteristics and drug utilization in separate SGLT2i and GLP-1 RA new-user cohorts of adults with CKD and type 2 diabetes in an earlier (1 January 2012-30 June 2021) and a later (9 July 2021-30 September 2023) period using Optum's de-identified Clinformatics^® Data Mart Database (Optum^® CDM).

Results: Compared with the earlier period new users, later period new users in both cohorts were older, had more severe CKD, used less intensive type 2 diabetes medication, and had better metabolic control; SGLT2i new users more frequently had no type 2 diabetes therapy before the index date and greater congestive heart failure prevalence; and GLP-1 RA new users had increased SGLT2i use and decreased insulin use.

Conclusions: These findings inform and contextualize future studies assessing cardiorenal outcomes for these and additional treatments, including finerenone, for individuals with CKD and type 2 diabetes.

Cardiorenal metabolic disease (CRMD) encompasses a cluster of interrelated conditions-including obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic dysfunction-associated steatotic liver disease (MASLD)-that share common pathophysiologic pathways and amplify morbidity and mortality risks. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated robust evidence across randomized controlled trials and real-world studies in improving glycemic control (mean glycated hemoglobin [HbA1c] reduction of 1.0-1.5%), inducing sustained weight loss (average 10-15%), and reducing major adverse cardiovascular events (by 26% in SUSTAIN-6 and 20% in SELECT). Its potential renal and hepatic benefits, including slower estimated glomerular filtration rate (eGFR) decline and reduction in liver fat content, highlight its suitability for integrated CRMD management. This consensus report was developed through a structured, multiphase Delphi process involving endocrinologists, cardiologists, nephrologists, hepatologists, and public health experts from across Saudi Arabia. A comprehensive literature search (PubMed, Scopus, and Saudi Digital Library [2016-2024]) prioritized high-quality evidence from randomized controlled trials (RCTs), systematic reviews, and regional data. The panel reached consensus on key recommendations: (1) early identification and holistic management are critical for effective CRMD control; (2) adults at risk should undergo systematic screening for metabolic, cardiovascular, renal, hepatic, and cognitive complications; and (3) semaglutide should be positioned as a cornerstone therapy given its multiorgan benefits and favorable safety profile. Implementation strategies emphasize the careful selection of patients, individualized dosing, patient education, and integration into national pathways. In alignment with Saudi Vision 2030, incorporating semaglutide into CRMD management, supported by provider training, multidisciplinary care models, and cost-effectiveness analyses, can significantly reduce the national burden of metabolic disease and CVD.

Introduction: Although there is a recognized negative interplay between metabolic dysfunction-associated steatohepatitis (MASH) and type 2 diabetes (T2D), the extent to which comorbid MASH exacerbates T2D complications is not well understood. This real-world cohort study evaluated whether the coexistence of these diseases is associated with increased risk of microvascular and macrovascular complications.

Methods: We identified eligible adults with T2D from the Optum^® Clinformatics^® Data Mart Database (2016-2024). Presence of MASH was determined using International Classification of Diseases, Tenth Revision, Clinical Modification coding, requiring ≥ 1 primary inpatient or outpatient diagnosis code. Patients with T2D and MASH were matched 1:1 with patients with T2D without MASH using propensity score matching to balance baseline characteristics. Fine-Gray models were used to estimate subdistribution hazard ratios (sHR) comparing the risk of microvascular and macrovascular T2D complications between both groups, while accounting for death as a competing risk. Stratified analyses were performed by glycemic control (glycated hemoglobin < 7% and ≥ 7%) and age (< 65 and ≥ 65 years).

Results: The study comprised 7396 and 6207 matched pairs in the microvascular and macrovascular complications cohorts, respectively. In this T2D population, mean (standard deviation) follow-up was 2.8 (2.0) years for patients with MASH and 2.4 (1.8) years for patients without MASH in both cohorts. Compared with patients with T2D without MASH, those with T2D and MASH had increased hazards of microvascular (sHR 1.19 [95% confidence interval (CI) 1.12-1.26]) and macrovascular complications (sHR 1.15 [95% CI 1.08-1.23]). A similar trend was observed for the stratified subgroup analyses.

Conclusion: Patients with T2D and MASH had higher hazards of microvascular and macrovascular complications versus those with T2D without MASH. These findings suggest that the presence of MASH accelerates T2D-related complications, creating a clinical imperative for integrated screening and management approaches to identify this high-risk population among patients with T2D.

Introduction: Traditional Indian cereal-based breakfast items have high glycemic index (GI) contributing to postprandial (PP) glucose spikes. Use of diabetes-specific protein supplement (DSPS) may reduce glycemic excursions. The study aimed to evaluate the effect of partially replacing breakfast with DSPS (Protinex Diabetes Care) on PP glycemic response.

Methods: Forty-two persons with type 2 diabetes mellitus (T2DM) participated in this randomized, controlled, open-label, crossover study. Participants consumed a test breakfast (DSPS in 200 ml milk + reduced portion of popular Indian savory breakfast (upma/poha)) or isocaloric control breakfast (upma/poha) for 5 days, with 3-day washout. PP glucose and insulin were assessed on the first day of intervention at baseline, 30, 60, 90, 120, 150, and 180 min after breakfast to calculate incremental area under the curve (iAUC0-3h) and delta peak (ΔCmax). During in-home use, macronutrient intake was assessed using dietary recalls, and glycemic variability (GV) was assessed using continuous glucose monitoring (CGM).

Results: Glucose iAUC0-3h and ΔCmax were 59% and 46% lower in test vs control, respectively. Insulin iAUC0-3h and ΔCmax did not differ significantly. During the test period, protein intake was significantly higher by 8.8 g; mean amplitude of glycemic excursions (MAGE)-a GV metric-was significantly lower. There were no gastrointestinal or adverse events. DSPS was well accepted by participants.

Conclusions: DSPS as a partial breakfast replacement improves blood glucose control without significantly impacting insulin response. In a real-world setting, DSPS enhances protein intake and reduces GV. These findings support DSPS as a practical, well-tolerated strategy for improving glycemic control and macronutrient intake balance in people with T2DM.

Trial registration: The trial was registered with Clinical Trials Registry India (CTRI) CTRI/2024/08/072006 and has been registered in the International Clinical Trials Registry Platform (ICTRP).

Introduction: This retrospective database study investigated trends in insulin and use of concomitant noninsulin glucose-lowering medication (NIGLM) among Japanese individuals with diabetes.

Methods: The study comprised two analyses: (1) a serial cross-sectional analysis of patterns in insulin treatment by year (database: Real World Data); and (2) a longitudinal retrospective cohort analysis that examined insulin treatment and individuals' characteristics (database: DeSC). Individuals initiating insulin in an inpatient or outpatient setting were followed up for 9 months (type 2 diabetes [T2D]) or 21 months (type 1 diabetes [T1D]) to evaluate treatment changes over time.

Results: The serial cross-sectional analysis included 4953 individuals (T2D, n = 4693; T1D, n = 260). The proportion of participants with T2D receiving concomitant NIGLMs increased from 31% in 2002 to 61% in 2021; from 2014 onwards, more than 30% of insulin-treated and basal-insulin-treated individuals treated with concomitant NIGLMs received dipeptidyl peptidase-4 inhibitors. Since 2018, use of concomitant NIGLMs in T1D has increased. The longitudinal retrospective cohort analysis included 27,492 individuals (T2D, n = 27,031; T1D, n = 461). Among participants with T2D who initiated insulin in an inpatient setting, 70.8% received bolus insulin at initiation, with this proportion declining to 17.3% after 9 months; proportions of participants receiving basal insulin and of those receiving basal-bolus insulin increased over the same period (6.3-31.1% and 17.0-23.4%, respectively). The majority of participants with T2D who initiated insulin in an outpatient setting received basal insulin at initiation (hospital, 53.9%; clinic, 58.9%). Among participants with T1D who initiated insulin in an inpatient setting, 57.9% received bolus insulin, and basal-bolus insulin was the predominant regimen after 1 month (85.0%); in outpatient settings, basal-bolus insulin was the predominant regimen throughout the study.

Conclusion: In Japan, the most prominent insulin regimen at initiation varied across settings in T2D but not in T1D; use of concomitant NIGLMs increased over time in both.

Introduction: Once-weekly efsitora resulted in similar efficacy and safety compared with daily basal insulins glargine or degludec in the treatment of adults with type 2 diabetes in the QWINT phase 3 development program. To fully assess once-weekly insulin's potential and address common barriers associated with insulin therapy (e.g., clinical inertia, fear of injections, treatment complexity), other aspects of the participants' treatment experiences were investigated using patient-reported outcome (PRO) measurements. The results of these PROs from QWINT-1 to -4 are presented here.

Methods: Six different PRO instruments were completed across the studies at primary timepoints and treatment period endpoint (QWINT-1, week 26/52; QWINT-2, week 26/52; QWINT-3, week 26/52/78; QWINT-4, week 26) by participants enrolled in the phase 3 QWINT clinical trials. The PRO instruments included Treatment Related Impact Measure-Diabetes (Trim-D) (QWINT-1, -2, and -3), Diabetes Treatment Satisfaction Questionnaire (DTSQ) (QWINT-1 and -3), Simplicity of Diabetes Treatment Questionnaire (SIM-Q) (QWINT-1, -2, and -3), Basal Insulin Experience (BIE) (all QWINTs), EQ-5D-5L (QWINT-2, -3, and -4), and Short Form-36 Health Survey Version 2(SF-36v2) (QWINT-2).

Results: Efsitora-treated participants demonstrated greater or similar improvements than comparators for most of the measured PROs at the primary timepoint in all four studies, particularly in QWINT-3 and -4 (prior insulin experience). Notably, for those treated with efsitora, there were significantly larger improvements than comparators in the PRO domains of treatment burden, daily life, diabetes management, compliance, satisfaction, and psychological health, as measured using the TRIM-D and DTSQc. Participants treated with efsitora had similar scores across both health-related quality of life measures, EQ-5D-5L and SF-36v2, at the primary endpoint when evaluated versus the comparator.

Conclusions: Participants in the QWINT-1 to -4 studies demonstrated a strong preference for efsitora, along with improved overall functioning, well-being, and treatment burden compared to daily basal insulins.

Clinical trial registration number for qwint studies: QWINT-1: NCT05662332; QWINT-2: NCT05362058; QWINT-3: NCT05275400; QWINT-4: NCT05462756.

Introduction: The current clinical reality and burden of obesity disease in Japan are poorly understood. To address this knowledge gap, in this real-world study we describe the characteristics of Japanese individuals with obesity disease (IwOD) and their obesity disease treatments using data from the Japan Obesity Research Based on electronIc healTh record (J-ORBIT) database.

Methods: This retrospective observational study (January 2019 to January 2024) assessed data of ≥ 18-year-old IwOD registered in J-ORBIT and diagnosed with primary obesity per the criteria of the Japan Society for the Study of Obesity (JASSO). IwOD were grouped according to the most advanced treatment received during the study period, including the index date: lifestyle intervention, pharmacotherapy, or bariatric surgery. Demographic and clinical characteristics, degree of weight reduction, and percent change in metabolic parameters from baseline to the latest follow-up timepoint were described.

Results: Among the 782 IwOD included in this study, 274, 487, and 21 had received advanced treatment in the form of lifestyle intervention, pharmacotherapy, and bariatric surgery, respectively. At baseline, across treatment groups the mean age ranged from 45 to 57 years, female proportion ranged from 45% to 76%, and body mass index (BMI) ranged from 31 to 39 kg/m², respectively. Across treatment groups, 62-69% had ≥ 3 obesity-related health disorders (ORHDs) at baseline. Mean follow-up periods in these groups ranged from 846 to 1211 days. Mean weight and BMI numerically decreased from baseline to follow-up across groups. In the lifestyle intervention , pharmacotherapy, and bariatric surgery groups, 38%, 45%, and 65% of IwOD achieved ≥ 3% weight reduction at the latest follow-up timepoint. IwOD with baseline BMI ≥ 30 kg/ m² tended to achieve greater weight reduction. Triglyceride, high-density lipoprotein-cholesterol, blood glucose, hemoglobin A1c, and uric acid levels tended to improve in IwOD with ≥ 3% weight reduction and greater categories.

Conclusion: Obesity-associated burden in terms of ORHDs was common among Japanese IwOD. Although IwOD tended to have the highest weight reduction after bariatric surgery, this treatment is indicated for a highly restrictive population and requires specific criteria to be met, leaving many IwOD with unmet needs. These IwOD may need pharmacotherapy for better weight management than that provided by current options.

As a leading complication of diabetes mellitus, diabetic neuropathy (DN) represents a major public health challenge due to its high prevalence and impact on patients' quality of life. The most common form, diabetic peripheral neuropathy (DPN), is characterized by progressive sensory loss, neuropathic pain, and autonomic dysfunction, all of which can significantly increase the risk of serious complications, such as foot ulcers and amputations. Traditionally, therapeutic strategies for DN have been largely limited to symptomatic management. However, recent advancements in diabetes therapy have opened promising avenues for disease-modifying interventions. In particular, incretin-based therapies and sodium-glucose co-transporter 2 (SGLT2) inhibitors have attracted increasing interest not only for their glucose-lowering effects, but also for their broader metabolic, renal, and cardiovascular benefits. In this narrative review, we synthesize emerging evidence on the potential role of these innovative therapies in the management of DN. Preclinical models, clinical trials and real-world observational studies strongly support the hypothesis that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and SGLT2 inhibitors may confer neuroprotective benefits. Beyond these established classes, novel agents such as dual and triple receptor agonists are currently being investigated. Although clinical data on their effects in DN are still limited, the simultaneous activation of multiple metabolic pathways suggests the potential for synergistic neuroprotective effects through enhanced regulation of glucose and lipid metabolism, attenuation of systemic inflammation and oxidative stress, improvement of mitochondrial function and reduction of neuronal damage. Although innovative diabetes therapies are still in early stages of development, they reflect a rapidly evolving landscape in the management of DN in the future.

Introduction: In patients with type 2 diabetes mellitus (T2DM), cardiovascular (CV) disease and chronic kidney disease (CKD) drive excess morbidity and mortality. Beyond glucose-lowering, incretin-based therapies may provide organ protection across the cardiorenal axis.

Methods: Narrative review of mechanistic pathways and randomized trials of GLP-1 receptor agonists (GLP-1RA), DPP-4 inhibitors, and newer dual/triple agonists, with targeted updates from recent pivotal programs (SELECT, FLOW, SOUL, SURPASS-CVOT) and emerging oral small-molecule GLP-1R agonists.

Results: Long-acting GLP-1RA reduces major adverse CV events (MACE), all-cause and CV death, heart-failure hospitalization, and kidney composites across CV outcome trials and meta-analyses. A 2019 pooled analysis and a 2025 update confirm consistent reductions in MACE and hard kidney outcomes independent of baseline HbA1c. In obesity without diabetes, semaglutide 2.4 mg lowered MACE in SELECT, expanding prevention beyond glycemia. In CKD with T2DM, FLOW showed that semaglutide reduced major kidney disease events and death from CV/kidney causes. In T2DM with ASCVD and/or CKD, the SOUL cardiovascular outcome trial (CVOT) demonstrated that oral semaglutide reduced three-point MACE versus placebo. In head-to-head CVOT, tirzepatide was non-inferior to dulaglutide on MACE while achieving greater weight and HbA1c reductions. Mechanistically, GLP-1R signaling spans Gs-cAMP/PKA, β-arrestin-dependent pathways, and additional routes (including Gq contexts), aligning with anti-inflammatory, natriuretic, and antifibrotic effects observed preclinically and clinically. Oral non-peptide GLP-1R agonists (e.g., orforglipron) show phase 2 efficacy but lack long-term CV/renal outcome data.

Conclusions: Incretin-based therapy has shifted care from glucose-centric targets to cardiorenal risk reduction. GLP-1RA are guideline-endorsed for patients with T2DM and high CV/renal risk irrespective of HbA1c; dual agonists and oral small-molecule agents may broaden indications pending definitive outcome evidence.