Diabetes Therapy最新文献

Background/objectives: The exact prevalence of and recent changes in diabetic polyneuropathy (DPN) and diabetic peripheral neuropathic pain (DPNP) in Japan are unclear. The oral gabapentinoid, mirogabalin besylate (mirogabalin), is effective with a good safety profile for DPNP with moderate-to-severe pain (numerical rating scale [NRS] scores ≥ 4). However, clinical evidence for mild pain (NRS scores ≤ 3) is unclear. The Dia-NeP study aims to examine: (1) the prevalences of DPN and DPNP and background factors in patients with type 2 diabetes mellitus (T2DM); and (2) the efficacy and safety of mirogabalin in patients with DPNP, including those with mild pain.

Methods: The Dia-NeP study is a multicenter, prospective study consisting of two parts, a baseline survey and an interventional study, to be conducted from March 2025 to August 2026 in patients with T2DM in Japan. The baseline survey is the observational study investigating the epidemiology of DPN and DPNP, and the interventional study is an exploratory, single-arm, open-label study of 12-week mirogabalin treatment. Of patients with T2DM enrolled in the baseline survey, those diagnosed with DPNP who have an NRS score for pain ≥ 1 will be included in the interventional study. The target sample size is 1000 to 3000 patients for the baseline survey and 100 for the interventional study.

Planned outcomes: The primary endpoint is the change from baseline in the NRS score at week 12 in the interventional study. The safety endpoint is adverse events. This study will not only show the latest prevalence of DPN and DPNP in Japan, but is also the first study to investigate the efficacy and safety of mirogabalin in patients with DPNP having mild pain, as well as moderate-to-severe pain, and is expected to provide useful evidence for future DPN and DPNP treatment.

Trial registration: Japan Registry of Clinical Trials (jRCTs031240623, registered 20/January/2025, https://jrct.mhlw.go.jp/en-latest-detail/jRCTs031240623 ).

Introduction: Diabetic ketoacidosis (DKA) is a potentially fatal diabetes complication marked by hyperglycemia, ketonemia, and acidosis that remains a major global healthcare burden despite advances in diabetes management. The aim of this study was to quantify the healthcare costs of DKA admissions at a tertiary hospital in the United Arab Emirates (UAE), and evaluate cost-effective preventative strategies.

Methods: A retrospective electronic record analysis of all DKA admissions from 2019 to 2023 at Tawam Hospital, Al Ain, was conducted after ethical approval from Tawam Human Research Ethics Committee, approval number MF2058-2023-916. Clinical characteristics, precipitating factors, length of stay, insurance status, and total inpatient costs were analyzed for all consecutive adult (≥ 16 years) DKA admissions over this period. The cost of DKA-related admission was compared to the price of insulin therapy in underinsured patients who are unable to afford insulin.

Results: There were 134 patients admitted with DKA (157 admissions) over 5 years (one DKA admission every 11.6 days). The mean hospitalization cost per DKA admission was 12,274 ± 10,213 USD (45,461 ± 37,826 AED), with an average length of stay of 10.2 ± 11.7 days (1203 USD [4,457 AED] per day). Insulin unaffordability, a preventable factor, led to 13.4% (21 cases) of admissions, incurring a total cost of 257,765 USD (954,686 AED). Underinsured patients demonstrated significantly higher ICU utilization (76.8% vs 52.5%, p < 0.01) and mean costs (14,269 USD [52,847 AED] vs 11,133 USD [41,235 AED], p = 0.07) compared to adequately insured patients. In comparison, the average cost of insulin is 38 USD (139.5 AED) per patient/month, indicating that the cost of one preventable DKA admission equals 27 years of insulin therapy. The overall mortality rate of DKA admissions was 4.5%.

Conclusion: DKA imposes a substantial economic and clinical burden in the UAE, with mean hospitalization costs of 12,274 USD per admission. While insulin unaffordability accounts for 13.4% of admissions (costing 257,765 over 5 years), infections represent the largest precipitating factor at 49.0%. Comprehensive DKA prevention requires a multifaceted approach: infection management education, ensuring insulin access for underinsured patients, and structured diabetes education. Our analysis suggests that addressing insulin affordability could be economically favorable, as preventing one DKA admission would offset 27 years of insulin costs. However, optimal resource allocation requires addressing all major precipitating factors to achieve meaningful reductions in DKA burden. Graphical abstract available for this article.

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: Healthcare expenditure for the treatment of type 2 diabetes mellitus (T2DM) in the Netherlands is high, mainly due to the cost of treating diabetes-related complications. Guidelines recommend sensor-based glucose monitoring systems for people living with T2DM and using insulin, but these are not reimbursed in the Netherlands for those using basal insulin only. The objective of this study was to assess the cost-effectiveness of glucose monitoring with FreeStyle Libre systems (FSL), compared with capillary-based self-monitoring of blood glucose (SMBG), for people living with T2DM on basal insulin, from the perspective of the Dutch publicly funded healthcare system.

Methods: The patient-level microsimulation model DEDUCE (DEtermination of Diabetes Utilities, Costs, and Effects) was used to estimate the incidence of complications and acute diabetes events (ADEs; hypoglycemia and diabetic ketoacidosis). The effect of FSL was modeled as a 0.5% reduction in glycated hemoglobin level, which DEDUCE translates to a lower rate of complications, and as reductions in ADEs and absenteeism. Costs (in 2024 euros) and utilities were discounted at 3% and 1.5%, respectively. Outcomes were assessed as quality-adjusted life years (QALYs).

Results: FSL was associated with 0.53 more QALYs than SMBG (12.77 vs. 12.24), at an additional cost of €8021. The resulting incremental cost-effectiveness ratio (ICER) for FSL versus SMBG was €15,181/QALY. The increased acquisition cost of FSL (€19,738) was partially offset by reductions in costs associated with complications, ADEs, and absenteeism. Probabilistic sensitivity analysis showed that FSL was 52% likely to be cost-effective at a willingness-to-pay threshold of €20,000/QALY, and > 99% likely at thresholds ≥ €40,000/QALY. FSL had an ICER of below €50,000/QALY in all scenarios investigated.

Conclusion: From a Dutch publicly funded healthcare system perspective, FSL can be considered to be cost-effective compared with SMBG for people living with T2DM on basal insulin therapy.

Introduction: Painful diabetic peripheral neuropathy (pDPN) affects approximately 25% of individuals with diabetes in the UK and remains underdiagnosed and suboptimally managed in primary care. The condition causes chronic pain, limits daily functioning, impairs quality of life, and increases the risk of complications like foot ulcers and amputations due to underlying neuropathy. Current care pathways are fragmented, leading to delays in diagnosis and limited access to evidence-based therapies. This article aims to address the challenges of screening, diagnosis, and management of pDPN in UK primary care by proposing a consensus-driven, five-step pragmatic strategy.

Methods: An expert panel of general practitioners and a diabetes nurse practitioner from across the UK convened to review and discuss strategies for improving pDPN care. Consensus was reached through an evaluation of barriers in clinical practice, supported by real-world experience and examples of innovative care delivery models, resulting in the development of practical recommendations and workflow.

Results: Key barriers identified include insufficient training of healthcare professionals in pDPN, underutilisation of validated screening tools such as the DN4 questionnaire, and inconsistent and outdated treatment guidelines. To address these challenges, a five-step approach was proposed to include screening high-risk patients using validated questionnaires, following up on these patients to enable early diagnoses, initiating early treatments with first-line therapies while monitoring responses, referring complex cases to secondary care on the basis of structured criteria, and ensuring coordinated follow-up to streamline and optimise care delivery. Case studies demonstrate the practical application of these strategies in improving early detection, treatment adherence, and long-term care for individuals with pDPN.

Conclusion: Current practices have fallen short in providing adequate care for one in four individuals with diabetes. Implementing a straightforward five-step approach can significantly improve diagnostic accuracy and treatment outcomes, reducing the burden of pDPN on both patients and society.

Introduction: Chronic kidney disease (CKD) progression is associated with a significant incremental economic burden. Previous work has demonstrated high accuracy of the laboratory-based machine learning model, Klinrisk, in predicting the risk of CKD progression. We sought to use the Klinrisk model to evaluate the association of risk of CKD progression with healthcare resource utilization (HRU) and costs of care in adults with type 2 diabetes and CKD.

Methods: This retrospective observational study included 413,177 eligible patients from Optum's electronic health records database (1/1/2007-9/30/2022). Patients were classified into low-, medium-, and high-risk groups based on their 2-year risk of CKD progression as predicted by the Klinrisk model. All-cause HRU and medical costs during the 1 year after CKD were estimated for each group.

Results: Of the 413,177 patients included, 110,399 (26.7%) were classified as low-risk of CKD progression, 253,188 (61.3%) as medium-risk, and 49,590 (12.0%) as high-risk. The observed risk of CKD progression at 2 years, 5 years, and 10 years was 18.6%, 36.5%, and 54.1% for high-risk patients, 3.7%, 11.7%, and 26.4% for medium-risk patients, and 1.5%, 5.7%, and 15.8% for low-risk patients, which were similar to the predicted risks of CKD progression. High-risk patients had higher HRU and more than 2-3 times higher costs than lower-risk patients. Inpatient costs were the major cost driver for high-risk patients.

Conclusions: The Klinrisk model accurately identified patients with type 2 diabetes and CKD requiring the most healthcare resources. Such tools can support the identification and targeting of high-risk patients for interventions that may lead to a more cost-effective model of care.

Introduction: IcoSema is under development as a once-weekly injectable combination therapy of icodec (basal insulin) and semaglutide (glucagon-like peptide 1 receptor agonist). This study assessed the pharmacokinetic characteristics of icodec and semaglutide following IcoSema administration vs. administration of icodec and semaglutide alone in Chinese individuals with type 2 diabetes (T2D).

Methods: In a randomized, double-blind, three-period crossover study, 20 Chinese individuals with T2D (18-64 years, body mass index 18.5-34.9 kg/m², glycated hemoglobin ≤ 9.0%) were given single subcutaneous administrations of IcoSema, icodec, or semaglutide separated by 6-9 weeks. Blood was drawn for pharmacokinetic measurement until 840 h post dose.

Results: Combining icodec with semaglutide had no impact on icodec pharmacokinetics. The ratio and 90% confidence interval of IcoSema/icodec was 1.04 [0.99;1.08] for area under the curve from zero to last quantifiable observation (AUC_0-t) and 1.02 [0.96;1.09] for maximum concentration (C_max), i.e., within the bioequivalence acceptance interval of 0.80-1.25. Likewise, combining semaglutide with icodec had no impact on semaglutide AUC_0-t (IcoSema/semaglutide 0.99 [0.94;1.05]). However, semaglutide C_max was higher for IcoSema vs. semaglutide alone (1.42 [1.31;1.53]) and occurred earlier for IcoSema (12 vs. 66 h). All three treatments were safe with no differences in frequency, severity or outcome of adverse events, or relationship to study product.

Conclusion: In Chinese individuals with T2D, icodec pharmacokinetics and semaglutide total exposure are unaffected when combining icodec and semaglutide in IcoSema. However, maximum semaglutide concentration is higher and occurs earlier with IcoSema. This information may help to ensure suitable dose recommendations for IcoSema.

Trial registration: ClinicalTrials.gov identifier, NCT05435677.