Diabetes Therapy最新文献

Despite revolutionizing diabetes care globally, continuous glucose monitoring (CGM) adoption in India remains limited, as a result of several economic, infrastructural, clinical, and sociocultural concerns. This narrative review aims to map unmet needs and propose practical, context-specific solutions. Continuous use of CGM remains the preferred approach for optimal glucose management and achieving long-term metabolic advantages, providing insights for proactive, data-driven, and preventive diabetes care. However, main barriers to CGM uptake include limited awareness among people with diabetes and healthcare providers, high costs, lack of reimbursement, limited device availability beyond major cities, and economic, infrastructural, and sociocultural access inequities across urban and rural populations. The psychological burden from frequent alarms, data fatigue, and stigma with noticeable or intrusive devices add to these challenges. Addressing these barriers necessitates a multifaceted strategy involving affordable, climate-adapted devices, interoperable digital ecosystems, India-specific reimbursement models, and robust educational infrastructure. The emergence of cost-effective CGM devices with a range of advanced features, such as predictive glucose algorithms and personalized pattern identification, is pivotal to this effort. These innovations improve clinical outcomes and quality of life by simplifying the user experience, addressing challenges, such as alarm fatigue while translating complex data into actionable insights, facilitating widespread CGM adoption in India.

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.

The incidence of youth-onset type 2 diabetes (Y-T2D) has been increasing over the last two decades in line with the growing rate of childhood obesity. Prior to 2019, the only United States Food and Drug Administration (FDA)-approved therapies for Y-T2D were metformin and insulin, and the current consensus guidelines recommend these therapies as first-line treatment. While metformin has a known safety profile and early efficacy for glycemic control, it has not been shown to prevent β-cell dysfunction or exogenous insulin requirements. Insulin is effective in treating hyperglycemia, but can result in hypoglycemia and further weight gain, worsening insulin resistance in Y-T2D. Furthermore, longitudinal data from participants treated early in their disease course with metformin and insulin demonstrate a cumulative incidence of at least one diabetes complication in most participants within 13 years of diagnosis. Over the last five years, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose co-transporter 2 inhibitors (SGLT-2is) have been added to the management toolbox for Y-T2D. However, further research is needed to determine the best timing and use for these medications for Y-T2D. The goal of this narrative review is to describe the current evidence for treatment with SGLT-2is and GLP-1RAs for Y-T2D within the first 1-2 years of the disease process.

Introduction: While glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are established for cardiorenal benefits in type 2 diabetes mellitus (T2DM), prior meta-analyses have not fully integrated cross-class comparisons or net benefit analyses with updated cardiovascular outcome trials (CVOTs).

Methods: We conducted a systematic review and meta-analysis of 17 CVOTs (N = 132,038; GLP-1RA: N = 73,263; SGLT-2i: N = 58,775) using PubMed and Cochrane CENTRAL. We uniquely synthesized major adverse cardiovascular events (MACE), hospitalization for heart failure (hHF), renal composites, and safety outcomes (e.g., retinopathy, genitourinary infections) with random-effects models for hazard ratios (HRs) and relative risks (RRs). Innovative graphical syntheses (tornado/scatter plots, risk curves) and net benefit calculations (absolute risk reductions [ARRs] minus absolute excess risks [AERs]) were employed. Risk of bias (RoB 2) and GRADE certainty were assessed.

Results: Both classes reduced MACE (HR 0.87, 95% CI 0.84-0.90; p = 0.73 for class difference). SGLT-2is were superior for hHF (HR 0.69 vs. 0.88, p < 0.0001) and renal outcomes (HR 0.68 vs. 0.79, p = 0.026). GLP-1RAs increased retinopathy (RR 1.18, AER + 6.5/1000); SGLT-2is increased genitourinary infections (RR 3.34, AER + 19.9/1000) and DKA (RR 2.67, AER + 1.2/1000). Amputation signals attenuated post-sensitivity analysis. Net benefits favored GLP-1RAs for MACE (+ 2.5/1000). For SGLT-2is, base-case estimates using genital-mycotic infections as the sentinel harm were marginal (hHF: - 4.9/1000; renal: - 1.9/1000), whereas sensitivity scenarios with alternative harms (e.g., volume depletion, amputation, DKA) yielded positive net benefits. GRADE certainty was high for efficacy, moderate for harms.

Conclusions: Our innovative integration of updated CVOTs, cross-class comparisons, and graphical risk-benefit tools refines therapeutic decision-making, highlighting tailored T2DM management based on patient-specific cardiorenal risks.

Trial registration: PROSPERO (CRD420251146788).

Cardiac arrest continues to be a predominant cause of mortality worldwide, necessitating its rapid identification, and intervention by reversible aetiologies to optimise successful outcomes. The established 4H 4T framework has served as a foundational guide for advanced life support (ALS) protocols since its formal introduction in the 2000 International Guidelines on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC), effectively targeting critical conditions such as hypoxia, hypothermia, hypo-/hyperkalaemia, hypovolaemia, tension pneumothorax, cardiac tamponade, thrombosis, and exposure to toxins. However, this framework inadequately addresses other significant factors: specifically hypoglycaemia and tachy- and bradyarrhythmias. Hypoglycaemia, a reversible and treatable metabolic state, poses substantial threats to cardiovascular stability, particularly in people with diabetes and in association with sepsis. It disrupts myocardial repolarisation, prolongs the QT interval, and may instigate the R-on-T phenomenon, which can precipitate life-threatening arrhythmias. Likewise, tachyarrhythmias and bradyarrhythmias often precipitate cardiac arrest, thereby warrant dedicated attention within ALS protocols. This paper advocates expanding the current 4H 4T framework to include hypoglycaemia and tachy- and bradyarrhythmias as critical and reversible causes of cardiac arrest (5H 5T). The rationale for such a paradigm shift is supported by evidence from clinical studies, case reports, and experimental models that demonstrate the adverse effect of these conditions on cardiovascular integrity and alert clinicians to look for these reversible factors. The inclusion of these factors into ALS protocols will necessitate revising resuscitation guidelines, modifying training for healthcare practitioners, and including systematic monitoring of blood glucose alongside routine assessment of cardiac rhythm during resuscitation procedures. Future research should focus on elucidating the pathophysiological mechanisms underlying these conditions, to establish operational thresholds for intervention, and validate their integration into resuscitation frameworks. By expanding the conceptualisation of reversible causes, the proposed 5H/5T framework would offer a more rational and practical approach to the management of cardiac arrest, to improve the survival and recovery of these critically ill patients.

Introduction: FreeStyle Libre (FSL) systems are effective and user-friendly glucose monitoring devices. This cost-effectiveness analysis compared FSL vs. self-blood glucose monitoring (SBGM) in patients with poorly controlled [hemoglobin A1c (HbA1c) > 8%] type 2 diabetes (T2DM) on basal insulin, from the Spanish National Health System perspective.

Methods: The DEDUCE model, which simulated 10,000 patients with T2DM over a 50 years' time horizon (annual discount rate = 3.00%), was adapted to the Spanish setting. The population characteristics, frequency of acute and chronic diabetic complications, costs (€, 2025) and utilities/disutilities proceeded from scientific literature and were validated by national multidisciplinary experts. The annual probabilities of acute events associated with SBGM were 17.02% for non-severe hypoglycemia (SHE) (€3.92; disutility = - 0.0016), 2.50% for SHE (€1031.69; disutility = - 0.0470) and 0.25% for ketoacidosis (DKA) (€2523.93; disutility = - 0.0470). The RECODe risk engine was used to model chronic diabetic complications (myocardial infarction [€1248.44-€31,013.22; disutility = - 0.0550]; heart failure [€1523.14-6505.08; disutility = - 0.1080]; stroke [€3187.92-7849.48; disutility = - 0.1640]; blindness [€2943.37; disutility = - 0.0740]; renal failure [€4057.05-42,757.39; disutility = - 0.2040]). According to the Spanish recommendations, a patient with SBGM required 2.5 reactive strips/day and 2.5 lancets/day (€0.57/strip; €0.14/lancet; VAT included). FSL (26 sensors/year; €3.00/day; VAT included) was associated with reductions of 58% in hypoglycemia, 68% in DKA, 83% in the use of strips/lancets, and an absolute decrease of 1.1% in HbA1c. Deterministic and probabilistic sensitivity analyses (SAs) were conducted.

Results: While SBGM yielded 9.18 quality-adjusted life years (QALYs) and total costs of €77,092 (glucose monitoring = €17,080; diabetic complications = €68,272), FSL yielded 9.98 QALYs and total costs of €61,447 (glucose monitoring = €8820; diabetic complications = €44,367). Compared with SBGM, FSL produced total cost savings of €15,645 and 0.80 additional QALYs per patient, being a dominant alternative compared to SBGM. FSL was found to be dominant in all SAs.

Conclusions: This analysis suggests that FSL, which provides better clinical outcomes at a lower overall cost, is a preferable alternative to SBGM among people with poorly controlled T2DM on basal insulin.