Diabetes Therapy最新文献

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.

Introduction: GLP-1 receptor agonists (GLP-1 RAs) are hypothesized to reduce peripheral arterial disease (PAD) complications through mechanisms, including enhanced cardiac function, improved cardiovascular risk factors and inflammation, and local vascular effects such as angiogenesis. We assessed the effectiveness of GLP-1 RAs in lowering the risk of major adverse limb events (MALE) among individuals with diabetes and diagnosed PAD.

Methods: This was a meta-analysis of a structured search of MEDLINE, PubMed, and SCOPUS databases until 16 June 2025. Eligibility criteria were randomized controlled trials of GLP-1 RAs reporting major adverse limb events from PAD. We identified five articles published up to June 2025 that met the inclusion and exclusion criteria. Study selection, data extraction, and quality assessment were carried out by two reviewers working independently and in duplicate, to assess eligibility and risk of bias, and extract data from eligible studies. Random-effects models were used to pool estimates across the included studies. Meta-analyses were performed using Cochrane-RevMan.

Results: Five studies were included in the meta-analysis, comprising 25,067 patients in total. There were 433 revascularization events. Compared with the control group, the overall log odds ratio for revascularization with GLP-1 RA treatment was 0.87 (95% confidence interval [CI]: 0.73, 1.05; p = 0.13). Two of the studies reported amputation rates (comprising 224 events), with an overall log odds ratio of 0.82 (95% CI: 0.53, 1.27; p = 0.37) for GLP-1 RA treatment.

Conclusions: In this meta-analysis of randomized trials, GLP-1 RAs were not associated with statistically significant differences in revascularization or amputation outcomes in individuals with diabetes and PAD.

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.

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: 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.

Introduction: For people with type 2 diabetes (T2D), combination therapy with a basal insulin and a glucagon-like peptide 1 receptor agonist (GLP-1 RA) can improve glycaemic control, lower hypoglycaemia risk, and improve adherence. IcoSema is the first once-weekly combination of basal insulin and GLP-1 RA in a single injection. To compare once-weekly IcoSema and once-daily IDegLira for the management of T2D in the absence of head-to-head trials, we performed a network meta-analysis (NMA).

Methods: A systematic literature review was conducted in November 2023, updated in August 2025, to identify randomised controlled trials (RCTs) of people with T2D, investigating basal insulin and GLP-1 RA combination therapies. Data were extracted for change from baseline in glycated haemoglobin (HbA_1c), body weight, systolic blood pressure, end-of-treatment basal insulin dose, rate ratio (RR) of clinically significant or severe hypoglycaemia and discontinuation due to adverse events (DDAEs). The NMA scope included multinational RCTs with evidence at 52 ± 4 weeks. Fixed and random effects Bayesian NMAs were fitted.

Results: At 52 weeks, compared with IDegLira, IcoSema was associated with significantly greater HbA_1c reduction (- 0.4%; 95% credible interval [CrI] - 0.56, - 0.24), significantly greater body weight reduction (- 3.2 kg; 95% CrI - 3.91, - 2.5), significantly lower daily insulin dose (- 9 units/day; 95% CrI - 13, - 5) and significantly lower rates of clinically significant or severe hypoglycaemia (RR 0.35; 95% CrI 0.26, 0.46). There was no difference in the odds of DDAEs. No 52 ± 4-week IGlarLixi trials were identified.

Conclusion: These results indicate that once-weekly IcoSema is an efficacious treatment option for adults with T2D requiring insulin intensification. IcoSema was associated with improved glycaemic control, weight reduction, and lower hypoglycaemia risk compared with once-daily IDegLira, as well as a reduction in insulin and injection requirements. Weekly IcoSema offers the potential to reduce treatment burden and increase adherence, thereby improving long-term disease control and patient outcomes.

The gut microbiota (GM) is a pivotal regulator of host metabolism and a contributor to the pathophysiology of obesity, type 2 diabetes (T2D), and metabolic syndrome (MS). Disruptions in GM composition and function are collectively termed dysbiosis. This review synthesizes current evidence on GM dysbiosis, moving beyond simple taxonomic associations, to examine functional drivers of metabolic dysfunction. Dysbiosis impairs metabolic health through several interconnected pathways: enhanced dietary energy extraction, compromised intestinal barrier integrity leading to metabolic endotoxemia, chronic low-grade "meta-inflammation," and the disruption of circadian rhythms and neuro-immune signaling. Beyond bacteria, dysbiosis of the gut virome and mycobiota may further modulate metabolic risk. Animal and emerging human studies indicate that reduced virome diversity and altered phage-bacteria interactions can amplify dysbiosis, promote inflammatory signaling, and impair metabolic homeostasis. Recognition of GM dysbiosis as a contributor to metabolic disease has prompted development of therapeutic strategies aimed at restoring microbial balance and function. These interventions span a spectrum from established clinical approaches with indirect microbiota effects to experimental therapies designed to directly manipulate microbial composition or activity. We evaluate the clinical readiness of GM-targeted therapies, including dietary patterns, prebiotics, probiotics, and fecal microbiota transplantation. While established metabolic treatments such as glucagon-like peptide-1 (GLP-1) receptor agonists and bariatric surgery significantly reshape the GM, direct microbial manipulations often yield variable results in human trials. We conclude that the future of metabolic management lies in personalized microbiomics, utilizing artificial intelligence and precision-based interventions to restore specific functional microbial deficits tailored to the individual host profile.

Introduction: Effective insulin therapy relies on proper injection technique and the correct use of insulin delivery devices. Despite recommendations for a single-use device, the pen needle reuse remains common. This study explored pen needle reuse patterns, reasons for reuse, and motivators to changing reuse behavior, in order to provide actionable insights for clinical education and patient-support interventions.

Methods: A cross-sectional online survey was conducted with 500 U.S. adults with type 1 diabetes (T1D) or type 2 diabetes (T2D) who inject insulin at least twice daily using an insulin pen and use insulin pen needles at least twice before replacing.

Results: Approximately 70% of survey participants reported using needles 2-5 times before replacing, and about 30% used them six or more times, with higher reuse among participants with T1D. Despite most participants reporting initial insulin injection education (86.8%), the majority indicated limited follow-up regarding injection practices. Specifically, 73.6% indicated their injection sites were never examined by a healthcare professional (HCP), 72.8% reported their injection technique had never been reviewed, and 66.2% reported their HCP had never asked them about injection site problems. The main reported reasons for needle reuse include convenience (64.2%), habit (46.2%), environmental/waste concern (40.8%), and cost (40.6%). The most motivating educational messages for changing reuse include those around A1c improvement and lipohypertrophy prevention, with the most trusted sources of information being endocrinologists, followed by primary care physicians (PCP), diabetes educators (known in the U.S. as diabetes care and education specialists), and peers.

Conclusions: Pen needle reuse is widespread and initial education alone is insufficient. Ongoing reinforcement and messaging from trusted HCPs, particularly around A1c and injection-site outcomes, provide a key opportunity to support behavior change.

Obesity is a major health concern, affecting over 1 in 8 people worldwide. Bariatric surgery (BS) is currently the most effective long-term treatment for morbid obesity. In addition to sustained weight loss, BS is beneficial in treating obesity related comorbidities including dyslipidemia and type 2 diabetes (T2DM). The beneficial effects of BS are a result of weight loss and surgery-induced shifts in the gut microbiota and its metabolites. At the same time, BS may also lead to complications and side effects. Abdominal pain is one of the most frequently reported complaints after BS with a prevalence of 33.8-54.4% within this patient group. However, in many patients the abdominal pain remains unexplained beyond gallstones, internal herniation, and ulcers. This raises the question whether the gut microbiota itself may play a direct role in the pathophysiology of unexplained abdominal pain. Over the years several studies have shown changes in the gut microbiota and related metabolites after BS. These include increased gut microbial diversity and altered microbial composition after BS. Higher abundances of Proteobacteria and Fusobacteria are reported, while a decrease in butyrate-producing Firmicutes is reported. Along with these changes in microbiota, BS causes higher plasma bile acid levels and altered short-chain fatty acid (SCFA) profiles. These metabolic shifts are believed to support weight control, glucose regulation, and lipid metabolism. More recently, specific microbial taxa and metabolite profiles were linked to abdominal complaints following BS. This suggests that dysbiosis and metabolites may play a role in unexplained abdominal pain after BS.

Introduction: Simultaneous pancreas-kidney (SPK) transplantation normalizes glycemia in patients with diabetes and end-stage kidney disease, yet data on continuous glucose monitoring (CGM) remain scarce.

Methods: We retrospectively analyzed CGM metrics in SPK recipients using FreeStyle Libre 2®, comparing pre- and post-transplant profiles.

Results: Among n = 19 recipients, only n = 14 continued CGM use after transplantation (n = 9 continuously during the entire study period). Within 1 month, all CGM metrics improved significantly, including increased time-in-range (54.21 vs. 83.85%) and time-in-tight-range (TITR; 33.45 vs. 69.77%), and reduced glucose variability (p < 0.05 for all comparisons), with stability over 24 months. Optimal graft function was associated with superior CGM outcomes, notably higher TITR and lower mean amplitude of glycemic excursions (MAGE; p < 0.05). However, hypoglycemia-related targets were not consistently achieved despite otherwise optimal graft performance.

Conclusions: SPK transplantation was linked to rapid and sustained improvement in CGM profiles. These findings underscore CGM's value for monitoring graft function and support its integration into post-transplant care to optimize metabolic outcomes.