Tirzepatide has demonstrated good efficacy and safety in the management of type 2 diabetes (T2D) in clinical trials. As the importance of early intensive intervention is known, the tirzepatide benefit for early glycemic and weight management (T-BEAT) study investigated the real-world effectiveness of tirzepatide in participants with early stage T2D in Japan. This in-progress, noninterventional, multicenter, observational study assesses the glycemic control of tirzepatide (5–15 mg once weekly) or oral semaglutide (7–14 mg once daily) in participants with T2D who were naive to oral antidiabetes drugs (OADs) (diet and exercise only) or received OAD monotherapy, excluding oral semaglutide. The primary endpoint is the mean change in glycated hemoglobin (HbA1c) from baseline after up to 12 months of treatment. Patient-reported treatment satisfaction and other secondary endpoints are also being investigated. Baseline characteristics of the participants are reported. In the tirzepatide group (N = 290), mean participant age was 55.2 (standard deviation [SD] 13.4) years, 45.2
Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) offer cardioprotection in type 2 diabetes mellitus (T2DM). We evaluated their monotherapy versus their combined use for prevention of myocardial infarction (MI) and stroke. Conducted according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 guidelines, five databases were systematically searched through November 2025 for studies evaluating use of SGLT2i and GLP-1RA in combination versus their monotherapy in adults with T2DM. Hazard ratios (HRs) for MI and stroke were pooled utilizing random-effects models. Subgroup interaction testing and grading of recommendations assessment, development, and evaluation (GRADE) certainty assessments were performed. Of the studies, eight comprising ten comparisons were included. Combination therapy was associated with a lower overall risk of MI (HR 0.79, 95 https://www.crd.york.ac.uk/PROSPERO/view/CRD420261320374 .
Prediabetes is a metabolic state that frequently precedes overt type 2 diabetes mellitus (T2DM) and is associated with an increased risk of micro- and macrovascular complications. Lifestyle modification remains the cornerstone of management, and several pharmacological agents, including metformin, pioglitazone, acarbose and glucagon-like peptide−1 receptor agonists (GLP-1 RAs), have demonstrated efficacy in delaying progression to T2DM. Sodium–glucose cotransporter 2 (SGLT2) inhibitors (often referred to as gliflozins) are increasingly being investigated in this context. The aim of this review is to summarise current evidence regarding the use of SGLT2 inhibitors in adults with prediabetes and to discuss the arguments for and against their routine clinical use. A narrative review of publications retrieved from the PubMed database, addressing the role of SGLT2 inhibitors in prediabetes, was performed. Original studies, meta-analyses, systematic reviews and high-quality narrative reviews up to February 2026 were considered for inclusion. Multiple studies have demonstrated that SGLT2 inhibitors improve insulin sensitivity, promote modest weight reduction, lower blood pressure and exert favourable effects on hepatic lipid metabolism. Two contemporary meta-analyses confirm that SGLT2 inhibitors reduce the incidence of new-onset T2DM in adults with prediabetes who also have heart failure or chronic kidney disease (CKD), with relative risk reductions of approximately 19–21
We aimed to describe the rationale, design, and overall baseline characteristics of the trial evaluating the efficacy, safety, and tolerability of survodutide in Chinese adults with overweight or obesity (SYNCHRONIZE™-CN, NCT06214741). In this 76-week, multicenter, randomized, double-blind, placebo-controlled, phase 3 trial, Chinese participants were randomized 1:1:1 to once-weekly subcutaneous survodutide (3.6 mg or 4.8 mg) or placebo plus lifestyle intervention. Participants with either body mass index (BMI) ≥ 28 kg/m2 or BMI ≥ 24 kg/m2 and at least one obesity-related complication were eligible. The primary endpoints were the percentage change in body weight and achievement of body weight reduction ≥ 5
Type 2 diabetes (T2D) and obesity are associated with substantial morbidity and healthcare spending. Although telehealth-delivered lifestyle interventions have demonstrated clinical benefits, evidence on their impact on healthcare costs and utilization remains limited. This study evaluated the association between participation in a comprehensive nutrition-first digital care model integrating individualized carbohydrate-reduced nutrition support, clinician-guided medication management, health coaching, and remote biometric monitoring on total healthcare costs and utilization over 1 year and 2 years. We conducted a claims-based, retrospective propensity score matched difference-in-differences analysis of cost and utilization outcomes among US adults with T2D or obesity who (1) enrolled in Virta Health’s Individualized Nutrition Therapy (INT) program or (2) had a primary care visit for either condition between 2017 and 2025. Per-member, per-month (PMPM) outcomes included inpatient, outpatient, and prescription medication costs, as well as inpatient, emergency department, primary care, cardiology, and endocrinology visits. For the T2D cohort only, PMPM costs for each diabetes medication were also evaluated. Among 3819 adults with T2D and 2761 adults with obesity, program participation was associated with 240 and256 PMPM reductions in total cost of care at 12 months, respectively (−230 and −189 PMPM over 24 months; all p < 0.001). Among adults with T2D, savings were driven by reduced inpatient visits and deprescription of sodium-glucose cotransporter 2 (SGLT2) inhibitors (66.8
Chronic venous disease (CVD) is a highly prevalent but often under-recognized condition, affecting up to 60
Clinical inertia and the complexity of basal insulin titration are major barriers to optimal glycemic control in adults with type 2 diabetes (T2D). A prototype of the Dexcom Smart Basal system known as basal therapy optimization (BTO), a continuous glucose monitoring (CGM)-informed basal insulin optimization system, was evaluated for its efficacy, safety, and impact on patient-reported outcomes (PRO). In this prospective, single-arm study, 14 adults with T2D (three initiating and 11 optimizing basal insulin) used the BTO system. The study consisted of three phases: a ten-day baseline, up to 35 days of active titration, and a 20-day post-titration follow-up. Outcomes included change in CGM-derived glycemic metrics (mean glucose, time in range [TIR], time above range [TAR], time below range [TBR]), fasting blood glucose (FBG), and PROs (diabetes treatment satisfaction, glucose monitoring satisfaction, and patient–doctor depth of relationship) assessed using validated questionnaires. Safety was also assessed by the number of adverse events. All participants completed the study. The BTO system generated 401 insulin dose recommendations, with 96.5
The phase 3 QWINT-3 study demonstrated that once-weekly insulin efsitora (efsitora) was noninferior to once-daily insulin degludec (degludec) in reducing glycated hemoglobin A1c (HbA1c) at week 26 (primary end point) in adults with type 2 diabetes (T2D) who had previously received insulin. A subgroup analysis of QWINT-3 participants from Japan is presented. QWINT-3 was a phase 3, multicenter, randomized, parallel-design, open-label study. Participants were randomized in a 2:1 ratio to receive efsitora or degludec. All participants from Japan were included in this preplanned subgroup analysis. End points investigated included changes in HbA1c from weeks 0 to 26 and throughout the treatment period (weeks 0–78), time spent in the glucose range from weeks 22 to 26 and during the initial dosing period (weeks 0−12), fasting blood glucose from weeks 0 to 78, and incidence and rate of hypoglycemia from weeks 0 to 78. Overall, 131 participants from Japan were randomized to efsitora (n = 87) or degludec (n = 44). Demographics and baseline characteristics were balanced between treatment groups. From weeks 0 to 26, HbA1c decreased from 7.64
Hypoglycemia is a common complication in people with type 2 diabetes mellitus (T2DM) treated with basal insulin, yet its true prevalence in real-world primary care remains underexplored. This study used blinded continuous glucose monitoring (CGM) to assess glycemic patterns in patients with T2DM on basal insulin-supported oral therapy (BOT) with insulin glargine 100 U/mL (Gla-100) in Spain. GPDetect was a prospective, multicenter, observational study in adults with T2DM treated with Gla-100 for ≥ 6 months in primary care. Participants underwent 14 days of blinded CGM (FreeStyle Libre® Pro iQ®). The primary objective of the present study was to estimate the proportion of patients with T2DM treated with Gla-100 whose TBR (glucose < 70 mg/dL) exceeded the internationally recommended threshold of 4
Continuous glucose monitoring (CGM) improves glycemic control and reduces acute events, yet adoption remains low despite expanded coverage. Real-world evidence shows that most eligible patients do not use CGMs, highlighting a gap between access and utilization. This commentary examines key barriers, including provider knowledge gaps, administrative complexity, workflow constraints, and persistent socioeconomic inequities. We argue that coverage expansion alone is insufficient to drive uptake. Coordinated strategies that support prescriber education, streamline processes, and integrate CGM into routine care are needed. Addressing these systemic and behavioral barriers is essential to realizing the full clinical and economic benefits of CGM at scale.
Diabetic foot (DF) is a severe and common complication of diabetes mellitus, involving peripheral neuropathy, vascular disease, immune-inflammatory disorders, and impaired tissue repair, with high amputation rates and a heavy medical burden. The Notch1 signaling pathway is highly conserved and participates in regulating cell proliferation, differentiation, apoptosis, angiogenesis, and inflammatory responses. Emerging evidence indicates that dysregulated Notch1 signaling is closely associated with the pathological progression of diabetic foot ulcers (DFU). This review systematically summarizes the role of Notch1 signaling in angiogenesis, inflammation, peripheral neuropathy, and cell fate regulation during DF pathogenesis, and discusses the potential therapeutic strategies targeting Notch1 pathway for DFU. We aim to provide new insights into the molecular mechanism and targeted therapy of DF. Infographic available for this article.
This study aimed to investigate the predominant pathogenic microorganisms, antimicrobial resistance patterns, and antibiotic sensitivity profiles of diabetic foot infections in the southern region of a province in central-eastern China, thereby providing evidence-based guidance for the rational use of antibiotics for treating foot infections in patients with diabetes. A retrospective analysis was performed on the clinical data from patients with diabetic foot infections who were treated at a large tertiary hospital between 1 July 2019 and 31 July 2024. Wound specimens were collected for bacterial culture and antimicrobial susceptibility testing, and both clinical and microbiological data were analyzed. A variety of pathogenic microorganisms, predominantly Gram-positive (G+) and Gram-negative (G−) bacteria, were isolated. The top five pathogens identified were Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Streptococcus agalactiae (group B), and Proteus mirabilis. As the Wagner grade increased, there was a shift in pathogens from G+ to G− bacteria, along with a rise in polymicrobial infections, primarily coinfections involving G+ and G− bacteria. The G+ bacteria exhibited high resistance to penicillin and certain cephalosporins but remained highly sensitive to vancomycin and linezolid. G− bacteria showed increased resistance to quinolones, carbapenems, and aminoglycosides while maintaining relative sensitivity to tigecycline and polymyxins. Fungal infections were highly sensitive to commonly used antifungal agents. Overall, significant variations in resistance to antimicrobials were observed among different strains, with some exhibiting notable multidrug resistance, underscoring the high risk of empirical monotherapy. The issue of antimicrobial resistance in foot infections associated with diabetes mellitus is becoming increasingly severe. Clinical treatment should be guided by antimicrobial susceptibility testing to ensure rational antibiotic use, improve therapeutic outcomes, reduce the emergence of resistant bacteria, and lower recurrence rates.
Global rates of insulin pen needle (PN) reuse in people with diabetes (PWD) vary across regions. However, it is estimated that more than 50
Type 1 diabetes (T1D) is associated with chronic kidney disease (CKD) and major adverse cardiovascular events (MACE). Contemporary data on the natural history of kidney function decline and the effect of therapies on slowing disease progression in T1D-related CKD are limited. We conducted a scoping review to describe the natural trajectory of kidney function and its effects in individuals with T1D in the USA. In our scoping review of observational studies and grey literature, we searched EMBASE (Ovid), Cumulative Index to Nursing and Allied Health Literature [CINAHL; Elton B. Stephens Company (EBSCO)], MEDLINE (Ovid), Scopus (Elsevier), Global Health (Ovid), and the Food and Drug Administration from inception to 25 April 2025. The study population included adults (age ≥ 18 years) with T1D in the USA. Our outcomes were change in estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), MACE (myocardial infarction, ischemic stroke, cardiovascular death, unstable angina, or heart failure hospitalization), and healthcare resource use (HCRU). We screened 6437 abstracts and selected 22 texts that matched our criteria. In one cohort, more than 50.0
The latest type 2 diabetes mellitus (T2DM) management guidelines from the UK National Institute for Health and Care Excellence (NICE; NG28) have raised the profile of sodium–glucose cotransporter-2 inhibitors (SGLT2is) so that they are now the preferred first-line therapy in combination with modified-release metformin (or as monotherapy where metformin is contraindicated/not tolerated) for most individuals. Previous NICE recommendations limited use to those with high cardiovascular disease (CVD) risk or existing CVD and/or kidney disease for first-line treatment or people with a need for additional glycaemic optimisation at later stages in the pathway. This change brings the guidelines in line with other national and international recommendations regarding SGLT2i use for the achievement and maintenance of glycaemic targets and lowering of progressive risk for cardiovascular, renal and metabolic (CVRM) complications. Yet, despite a plethora of evidence supporting the role that SGLT2is can play in sustaining long-term health outcomes in people with T2DM, prescribing data from real-world clinical practice show that these therapies are under-prescribed, particularly among those populations most likely to benefit from their use (including individuals with CVD or high CVRM risk). This latest narrative review from the Improving Diabetes Steering Committee examines the place of SGLT2is within the latest NG28 guidelines and likely reasons for suboptimal SGLT2i use, providing pragmatic advice on appropriate approaches to initiation and management in daily practice and setting perceived risks into context against the potential benefits. Practical tools for healthcare professionals and people with T2DM are included, and the Committee’s previously published SGLT2i Prescribing Decision Tool for T2DM Management has been updated and aligned with the most recent guidelines with the aim of providing a helpful and high-quality quick reference resource.
Real-world studies have demonstrated the effectiveness of automated insulin delivery systems in managing people with type 1 diabetes (T1D) worldwide. However, data on the effectiveness of such systems in the management of people with T1D in Greece have previously been lacking. This retrospective analysis sought to address this by providing real-world insights into the impact of the MiniMed 780G system on the glycemic control of people with T1D in Greece. Data from MiniMed 780G systems, uploaded to the CareLink Personal Software program between January 2024 and January 2025 by 2284 users with T1D in Greece, were collected and analyzed. Outcomes considered included glycemic control measures such as time spent in target ranges, glucose management indicator (GMI), and international glycemic control targets. Data were analyzed across different age groups (≤ 15 years, 16–55 years, ≥ 56 years), with additional analyses of cohorts using recommended optimal settings (ROS), users with data from before and after the initiation of the advanced hybrid closed-loop system, and users with 12 months of data. Across the overall cohort, the mean (standard deviation [SD]) time in range (TIR) was 75.4
Automated insulin delivery systems are effective for the management of type 1 diabetes (T1D). However, analyses of how such effectiveness translates into real-world practice in Spain are lacking. The aim of this study was therefore to examine real-world data generated by users of the MiniMed 780G system with T1D in Spain. The CareLink Personal software program was used to collect data from 16,392 users of the MiniMed 780G system. Outcomes assessed included measures of glycemic control. Comparisons were made between age groups and between pre- and post-advanced hybrid closed-loop (AHCL) system initiation. Additionally, longitudinal data from 12 months of continuous usage were analyzed. Overall, the mean time in range (TIR) was 75.9
Type 2 diabetes mellitus (T2DM) imposes a clinical and economic burden, largely due to its long-term micro- and macrovascular complications. To prevent these complications, treatment adherence is essential. The aim of this study was to analyse basal insulin adherence and its clinical and economic repercussions in patients with T2DM in Spain. Retrospective, descriptive observational study using the Spanish Health Improvement Network (THIN®) database. Adult patients with T2DM, a registry entry of first basal insulin prescription from January 2014, and prescription/dispensation records between January 2014 and January 2024 were included. Adherence was estimated as proportion of days covered ≥ 80
Obesity is a multifactorial condition that is not well captured by conventional anthropometry. Emerging frameworks, including the Lancet Commission approach, objectively stratify obesity and provide a more clinically informative characterization of the burden. The present study compares obesity estimates based on conventional BMI criteria with those derived using the revised framework and examines the distribution and determinants of pre-clinical and clinical obesity (CO) among older Indian adults. We used data from the first wave of the Longitudinal Aging Study in India (2017–2018), including 59,854 adults aged ≥ 45 years. A high body mass index (BMI; > 25 kg/m2) was used to estimate the conventional obesity burden. Pre-clinical obesity and CO were defined using framework guidance and based on variables available in datasets. Weighted prevalence and multivariable logistic regression estimates were calculated using Stata version 16.0. Weighted prevalence of high BMI was 27.1
Maturity-onset diabetes of the young (MODY) is a rare monogenic form of diabetes characterized by impaired insulin secretion and genetic and clinical heterogeneity. Accurate molecular diagnosis enables precision medicine by guiding gene-specific treatment, improving glycemic control, and avoiding unnecessary therapies. Since our previous systematic review in 2020, new studies have further clarified therapeutic strategies and emerging treatment options. This review updates the evidence on pharmacological management of MODY and its clinical implications. A systematic review was conducted following PRISMA 2020 recommendations. PubMed was searched for studies published between April 2020 and October 2025. Eligible studies included individuals with genetically confirmed MODY receiving pharmacological treatment, therapeutic switches, or adjunctive therapies. Data were extracted and synthesized qualitatively due to heterogeneity in study design and outcome reporting. Ninety-one studies were included. Strong evidence confirms sulfonylureas (SUs) as first-line therapy in Hepatocyte Nuclear Factor 1A (HNF1A)-, Hepatocyte Nuclear Factor 4A (HNF4A)-, ATP-binding cassette transporter sub-family C member 8 (ABCC8)-, and potassium inwardly rectifying channel subfamily J member 11 (KCNJ11)-MODY, frequently enabling improved glycemic control and transition from insulin. Glucokinase (GCK)-MODY remains managed without pharmacological treatment outside pregnancy, but dorzagliatin, a novel agent acting as a glucokinase activator, may further expand precision treatment approaches. Insulin remains the mainstay of treatment in Hepatocyte Nuclear Factor 1B (HNF1B)- and Insulin (INS)-MODY, although adjunctive therapies may provide benefits. While SUs are supported by consistent observational evidence, the role of incretin-based therapies and sodium-glucose co-transporter 2 inhibitors remains exploratory, largely based on small studies and case reports. A major limitation of the available evidence is the predominance of small, heterogeneous observational studies, which limits the strength and generalizability of therapeutic recommendations. Recent literature largely confirms existing genotype-guided treatment recommendations while suggesting expanded therapeutic options for selected MODY subtypes. Precision medicine based on molecular diagnosis remains essential for optimal management.
