The purpose of this study was to assess the efficacy of an educational intervention based on the Behavior Change Wheel (BCW) framework for individuals with type 2 diabetes mellitus (T2DM) on dietary and physical activity recommendations in a Spanish region.

A two-arm pragmatic randomized pilot trial was developed. The intervention consisted of a 6-month period with three components: face-to-face counseling, a phone call, and specially designed written guidelines focusing on dietary and physical activity recommendations The primary outcome was changes in dietary and physical activity recommendations. The secondary outcome, the impact of the intervention on HbA1c levels, body mass index, and the frequency of consultations to primary care.

n=208 patients were recruited. Individuals in the intervention experienced a significative improvement in adherence to dietary recommendations (+0.52; p-value<0.001), physical activity (+0.79; p-value<0.001), and a decrease in HbA1c levels (0.11 %; p-value=0.04).

The 6-month intervention, designed for T2DM patients and based on the BCW model, has demonstrated effectiveness in improving adherence to healthy dietary and physical activity recommendations, as well as reducing HbA1c levels.

Background/Objectives: Type 2 diabetes (T2D) prevalence is rising worldwide. Despite numerous efforts to address the condition, many initiatives fall short due to limited consumer engagement. Involving people with lived experience in healthcare design is increasingly recognized as an effective strategy for improving diabetes management. Aim: To understand the unmet needs of people with T2D in self-managing their condition through the establishment of a Consumer Reference Group (CRG). Methods: The CRG was established using a standardized approach advised by Monash Partners, with specific terms of reference for consumer engagement. A face-to-face training workshop was conducted to develop consumers' capacity to co-design T2D interventions. Two focus groups were held to explore consumers' unmet needs and propose potential solutions. An inductive thematic analysis was performed. Results: Ten adults (three females/seven males; 58-78 years old) with T2D participated. Four main themes emerged: (1) misinformation; (2) limited guidance; (3) challenges in self-management; and (4) gaps in prevention and screening. Participants reported difficulties in maintaining motivation, balancing T2D management with other life commitments, and addressing mental health concerns. They reported feeling misinformed and inadequately supported by healthcare professionals and diabetes organizations, often relying on conflicting sources of information. Participants from culturally and linguistically diverse (CALD) backgrounds noted a lack of tailored dietary information. Proposed solutions included better training for primary care providers, reinforcing the role of diabetes nurse educators, expanding mental health support, and collaborating with CALD communities to provide culturally appropriate dietary information. Conclusions: These insights are critical for developing consumer-driven interventions that are responsive to the real-world needs of people living with T2D.

Whilst insulin therapy errors are commonly reported in hospital and can cause significant negative outcomes for people with diabetes, there is no standardised approach to identifying when and why these errors occur within complex inpatient settings.

This scoping review was conducted to explore and map the types and classification of reported insulin errors in the care of people with diabetes in hospital inpatient settings and to identify potential interacting components/factors associated with these errors.

The review followed the methodological approach of the Joanna Briggs Institute for scoping reviews. Published and unpublished literature (grey) in the English language were searched from January 2000 to July 2024 on Medline, CINAHL, Embase and other relevant websites. Eligible studies were those reporting insulin errors occurring in hospital during the treatment of people who had diabetes. A new framework was developed for examining insulin errors (RESILIENT - interacting-components-in-insulin-use-in-hospital). This was applied to categorise incidents and interacting components identified. Results were summarised graphically and descriptively.

A total of 124 peer-reviewed publications and reports were included. Only forty-nine studies attempted to classify the type of errors reported and they varied considerably in terminology and focus. Insulin errors were most frequently reported at the prescribing, administration, communication/documentation and medication review stages. Common factors associated with reported insulin errors included: time-critical coordination of insulin related tasks (for example coordination of glucose monitoring, meal delivery and mealtime insulin administration; prescribing and medication review; intravenous insulin infusion management); capability at point of care, staff knowledge, non-adherence to guidelines/recommendations; teamwork, communication gaps or errors; patient factors; organisational processes/systems, education and training; equipment (e.g. lack off system integration, right equipment at point of care).

The review highlighted considerable heterogeneity in approaches to identifying and classifying insulin errors in the literature. This review identified incidents occurring in areas of the insulin process which have been previously rarely explored. Further studies are needed, using standardised approaches which capture the complexity of insulin errors within the hospital system, to support the development of interventions which improve insulin safety. Use of RESILIENT Framework could offer a more standardised method of data collection and analysis of insulin errors.

The protocol was registered at the Centre for Open Science (https://osf.io/nmd8a).

A novel approach to identifying, classifying & exploring insulin errors for people with diabetes in hospital @_ChristinaLange.

Background and Objectives: Elevated blood sugar poses an increasingly significant challenge to healthcare systems worldwide. We aimed to assess the efficacy of the SGLT-2i class in achieving metabolic control in patients with T2DM within a real-world standard-of-care regimen. Material and Methods: A prospective analysis was conducted over 6 months including individuals receiving care in an outpatient department, with baseline assessments and follow-ups at 3 and 6 months. Results: A total of 280 patients were assessed, with a mean age of 63.69 ± 9.16, 53.9% of which were males, with a mean DM duration of 9.06 ± 5.64 years, and a DM duration varying from 6 months to 24 years. Discussion: Real-world evidence bridges the gap between guidelines and practice. It emphasizes the need to overcome clinical inertia in order to optimize patient outcomes and contributes to the body of evidence supporting the efficacy of fixed-dose SGLT-2i combinations in managing T2DM and associated comorbidities. Conclusions: We demonstrate the significant clinical and therapeutic impact of SGLT-2i in T2DM patients in a real-world setting. This class of medication not only positively influences glycemic and weight control but also reduces CV risk factors and visceral adiposity.

Impaired endothelial function has been associated with vascular complications in type 2 diabetes (T2D), but its role in T2D-related heart failure (HF) remains indeterminate. The aim of this study was to assess selected markers of endothelial function in T2D patients with acute decompensated HF.

A pilot prospective study on patients with acute decompensated HF requiring in-hospital admission was carried out. The vascular endothelial growth factor (VEGF), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) were assessed at admission and after decongestion. Subsequently, differences in these markers between T2D and non-diabetic (ND) patients were studied.

In total, 39 patients (21 with T2D and 18 ND patients) were enrolled. Twenty-eight patients presented with preserved ejection fraction (EF), and 11 presented with reduced EF. Looking at the VEGF levels in T2D patients, on admission, a median of 233.0 pg/mL (1.7-598 pg/mL) was found compared to 106.0 pg/mL (1.7-888 pg/mL) in ND individuals; the differences reached statistical significance (p = 0.04). There were no significant differences in VEGF levels after decongestion, and in VCAM-1 (2237 ± 1195 vs. 2699 ± 1093 ng/mL, p = 0.37) and ICAM-1 (596 ± 268 vs. 638 ± 437 ng/mL, p = 0.79) levels between T2D and ND patients upon admission and after decongestion. The value of EF (preserved or reduced) affected the VEGF levels upon admission.

This study identified significantly higher VEGF levels upon admission due to acute decompensated HF in T2D patients.

The kidneys may be susceptible to ectopic fat and its lipotoxic effects, disposing them to chronic kidney disease (CKD) in type 2 diabetes (T2D). We investigated whether the kidney parenchyma fat content and kidney sinus fat volume would be higher in persons with T2D and CKD.

Cross-sectional study including 29 controls, 27 persons with T2D and no CKD, and 48 persons with T2D and early CKD (urine albumin creatinine ratio (UACR) ≥ 30 mg/g). Kidney parenchyma fat content and kidney sinus fat volume were assessed using magnetic resonance spectroscopy and Dixon scans respectively.

In the control, T2D without CKD and T2D with CKD groups, respectively, median [1st - 3rd quartile] UACR was 5 [4 - 6], 6 [5 - 10] and 95 [43 - 278] mg/g. and mean ± standard deviation estimated glomerular filtration rate was 89 ± 11, 94 ± 11 and 77 ± 22 ml/min/1.73m2. Kidney parenchyma fat content was, respectively, 1.0 [0.5-2.4], 0.7 [0.2-1.2], 1.0 [0.3-2.0] % (p = 0.26). Kidney sinus fat volume was 2.8 [1.6-7.6], 8.0 [4.7-11.3], 10.3 [5.7-14.0] ml (p < 0.01). Around 90 % of T2D participants received a sodium-glucose cotransporter-2 inhibitor or glucagon-like peptide-1 receptor agonist.

In a setting of modern, multifactorial T2D management, kidney parenchyma fat content, evaluated with magnetic resonance spectroscopy, was similar among healthy controls and persons with T2D irrespective of CKD status. Still, kidney sinus fat volume was higher in the presence of T2D and higher still with CKD.

Due to their ease of synthesis and large specific surface area, Ni(OH)2 nanosheets have emerged as promising electrochemical sensing materials, attracting significant attention in recent years. Herein, a series of oxy-hydroxides based on Ni(OH)2 nanosheets, including NiOx/Ni(OH)2@NF and (MNi)Ox/Ni(OH)2@NF (M = Co, Fe, or Cr), are successfully synthesized via the electrochemical oxidation and incorporation strategies. Electrochemical tests demonstrate that these Ni(OH)2-based oxy-hydroxides exhibit excellent electrochemical oxidation activity for glucose in alkaline electrolyte. Among these, (CoNi)Ox/Ni(OH)2@NF displays higher sensitivity of 3590.3 μA mM-1 cm-2 across a broad linear range of 10 μM to 1.14 mM, with a rapid current response time of less than 4 s. The superior sensing performances of (CoNi)Ox/Ni(OH)2@NF are attributed to the formation of abundant Ni3+ species and reactive-O atoms due to the electrochemical oxidation, and the synergistic effects of Co/Ni active sites resulting from the electrochemical incorporation process. In addition, the (CoNi)Ox/Ni(OH)2@NF demonstrates good stability and reproducibility for glucose sensing. This work fully leverages the significance of surface reconstruction of Ni(OH)2, providing new insights for the application of transition metal-based oxy-hydroxide materials in bio-sensing.

Type 2 diabetes mellitus (T2DM) represents a major healthcare condition of the 21st century. It is characterised by persistently elevated blood glucose occurring as a result of peripheral insulin resistance and reduced insulin production which may lead to multiple long-term health conditions such as retinopathy, neuropathy, and nephropathy. The estimated number of individuals suffering from diabetes mellitus (DM) is expected to rise to 591 million by the year 2035 with 4.4 million in the United Kingdom (UK) alone, 90% of which is attributed to T2DM. Moreover, a significant proportion of individuals may have undetected diabetes mellitus, especially among those presenting with symptoms of ischaemic heart disease (IHD). This is particularly important in those individuals presenting with acute coronary syndromes (ACS) who are at the highest risk of complications and sudden cardiac death. Identifying abnormal levels of common biochemical markers of diabetes, such as capillary blood glucose or glycated haemoglobin (HbA1c) in these patients is important for early diagnosis, which will then allow for timely intervention to improve outcomes. However, a significant proportion of individuals who meet the criteria for the diagnosis of diabetes remain undiagnosed, representing missed opportunities for early intervention. This may result in a prolonged period of untreated hyperglycaemia, which can result resulting in significant further microvascular and macrovascular complications. There is an increased risk of IHD, heart failure, cerebrovascular accidents (CVA), and peripheral artery disease (PVD). These account accounting for 50% of deaths in patients with T2DM. Cardiovascular diseases in the context of diabetes particular represent a significant cause of morbidity and mortality with a two to three times higher risk of cardiovascular disease in individuals with T2DM than in those without the condition normo-glycaemia. In the United Kingdom UK alone, around 120 amputations, 770 CVA, 590 heart attacks, and more than 2300 presentations with heart failure per week are attributed to diabetes DM. with One 1 in six 6 hospital beds and around 10% of the healthcare budget may be being spent on managing diabetes DM or its complications. Therefore, it represents a significant burden on our healthcare system.

The management of Type-2 Diabetes Mellitus (T2DM) remains challenging in cases of poor glycemic control despite triple Oral Hypoglycemic Agent (OHA) therapy. This prospective cohort study aimed to assess the effectiveness of Empagliflozin as part of a quadruple OHA regimen over a 7-year follow-up period in 575 adult patients with uncontrolled T2DM on a triple OHA regimen and who were unwilling to initiate insulin therapy. Overall, 92.5% of patients achieved their target HbA1c levels. Significant reductions were observed in all glycemic parameters after 68 months (p < 0.001). Weight and BMI significantly decreased, whereas waist circumference remained unchanged. Lipid profiles showed significant improvements in total cholesterol, LDL, and triglycerides, while HDL levels did not change significantly. Blood pressure trends revealed significant reductions in both diastolic blood pressure (DBP) and mean arterial pressure (MAP), though systolic blood pressure (SBP) remained relatively stable. Our study indicates that adding empagliflozin to a drug regimen consisting of multiple OHAs can effectively control glycemia in T2DM patients with more pronounced target achievement (< 7%) and HbA1c reduction along with improvement in cardiometabolic parameters, suggesting its potential as a promising alternative for long-term glycemic management.

Artificial intelligence (AI) platforms can potentially enhance clinical decision-making (CDM) in primary care settings. OpenEvidence (OE), an AI tool, draws from trusted sources to generate evidence-based medicine (EBM) recommendations to address clinical questions. However, its effectiveness in real-world primary care cases remains unknown.

To evaluate the performance of OE in providing EBM recommendations for five common chronic conditions in primary care: hypertension, hyperlipidemia, diabetes mellitus type 2, depression, and obesity.

Five patient cases were retrospectively analyzed. Physicians posed specific clinical questions, and OE responses were evaluated on clarity, relevance, evidence support, impact on CDM, and overall satisfaction. Four independent physicians provided ratings using a 0 to 4 scale.

OE provided accurate, evidence-based recommendations in all cases, aligning with physician plans. OE was scored on a scale of zero to four, where zero was very unclear, and four was very clear. Mean scores across cases were clarity (3.55 ± 0.60), relevance (3.75 ± 0.44), support (3.35 ± 0.49), and satisfaction (3.60 ± 0.60). However, the impact on CDM was limited (1.95 ± 1.05), as OE primarily reinforced rather than modified plans.

OE was rated high in clarity, relevance, and evidence-based support, reinforcing physician decisions in common chronic conditions. While the impact on CDM was minimal due to the study's retrospective nature, OE shows promise in augmenting the primary care physician. Prospective trials are needed to evaluate its utility in complex cases and multidisciplinary settings.

Cardiovascular disease (CVD) is a leading cause of mortality, affecting ∼18 million individuals each year. Obesity and type 2 diabetes mellitus in particular, both chronic metabolic disorders, are risk factors for CVD. The salutary effects of physical activity in preventing and ameliorating CVD have long been acknowledged, as it improves glucose and lipid homeostasis, alongside attenuating oxidative damage, increasing mitochondrial function, and ultimately improving cardiac function. Exercise serves as a catalyst for the secretion of extracellular vesicles (EVs), facilitating inter-tissue communication, by which tissues can deliver important signals from one tissue to another. In recent years, an increasing number of studies have focused on the cargo encapsulated within exercise-derived EVs, as well as the orchestration of inter-tissue crosstalk aimed at modulating metabolism and tissue function in CVDs. The precise mechanisms underpinning the cardioprotective properties of exercise-derived EVs, however, remains only partially elucidated. This review explores novel EV based therapeutic options in CVD and, in particular, EVs derived from models of exercise to alter metabolism and enhance cardiovascular outcomes.

SGLT2 (Sodium-Glucose Co-transporter 2) inhibitors, also known as gliflozin class, are a novel family of oral drugs being used to treat type 2 diabetes. SGLT2 inhibitors can work alone or in conjunction with other medications. This class includes five drugs, including canagliflozin, ertugliflozin, sotagliflozin, dapagliflozin, and empagliflozin. SGLT2 inhibitors inhibit the SGLT2 cotransporter in the proximal tubules of the kidney, reducing glucose and sodium reabsorption. It promotes the elimination of sugar in urine (diabetes mellitus) and lowers blood sugar levels. SGLT2 inhibitors also have pleiotropic effects on cardiac and renal function, broadening their therapeutic applications in heart failure. Despite the clinical benefits, regulators have placed secondary warnings in product information since the medications first hit the market. SGLT2 inhibitors, in particular, have had a significant impact on a variety of risk factors. This can lead to hypoglycaemia, urinary tract infections, diabetic ketoacidosis, lower limb amputation, and fractures. Although some of these events are uncommon, they can lead to severe and deadly consequences; therefore, patients must be closely monitored. In general, SLGT2 inhibitors are an efficient diabetes treatment with strong cardiovascular and renal protection and a favourable safety overview. This review sought to summarise the safety overview of commercially available SGLT2 inhibitors.

To present a study protocol for the development of an intervention to enhance safe insulin use for older or frail adults undergoing a surgical admission to hospital.

Following the United Kingdom's Medical Research Council and National Institute for Health and Care Research Frameworks for development and evaluation of complex interventions; this qualitative study will use a co-design approach using design thinking, to develop a theoretical model for the intervention.

Non-participatory observations, interviews and co-design workshops will be conducted with older or frail individuals with diabetes, their caregivers and healthcare staff responsible for their care during surgical admissions at a single National Health Service hospital in England. We will utilise their experiences and perspectives to establish priorities and generate ideas for the development of a conceptual model aimed at supporting the insulin safety review process in hospitals. Data will be analysed using framework analysis. People with diabetes were involved in the design of this study. The protocol was approved by the East-Midlands-Derby Research Ethics Committee (24/EM/0022). Study registered on Open Science Framework: https://osf.io/4wvu5.

Results of this study will be shared with study participants and disseminated through presentations at conferences/meetings and peer-reviewed publications.

This article outlines the methodology for the planned study which will employ a novel methodology to tackle the problem of hospital insulin safety. Its findings will contribute to a better understanding of the multiple interacting components implicated in hospital insulin use (patient, staff, context) and support further work around system-based strategies to enhance insulin safety resilience in hospital.

Ministry of Health (MOH) Malaysia stakeholders seek primary care access to sodium-glucose cotransporter 2 inhibitor (SGLT2i). Addressing this required a complex decision, selecting among three SGLT2i for two different indications and two practice settings. The options include expanding the existing SGLT2i (empagliflozin) in the MOH Medicines Formulary to primary care and/or having dapagliflozin and/or luseogliflozin as alternatives. This study aimed to conduct a multiple health technology assessment (HTA) to determine the SGLT2i of choice for the MOH setting.

The clinical benefits of SGLT2i were assessed through a systematic literature review and affordability was assessed through the development of three budget impact analysis models simulating seventy scenarios. Each model varied by prescribing indications, restrictions, and SGLT2i involved (M1: glycemic control, HbA1c between 6.5 percent and 10 percent, empagliflozin-dapagliflozin-luseogliflozin; M2: cardiovascular benefits, HbA1c less than 10 percent, empagliflozin-dapagliflozin; M3: a composite of M1 and M2). The outcome of the HTA was presented to the MOH decision-makers.

Although there was no significant difference in glycemic control between the SGLT2i, differences exist in cardiovascular benefits conferred. Despite having scenarios with lower net budget impact (NBI) in the M1, M2, and M3 models, decision-makers decided to expand empagliflozin use to primary care setting and add dapagliflozin for hospital-only setting for both indications [NBI of $4.38 mil] due to empagliflozin's advantage in reducing risk for cardiovascular death and prior experience of its use in MOH.

The multiple HTA approach guided the complex decision-making process by providing a holistic understanding of the decision's impact.

Despite the slow, progressive nature of NAFLD, the number of patients with NAFLD-related cirrhosis has significantly increased. Although the management of patients with cirrhosis is constantly evolving, improving the prognosis of patients with NAFLD-related cirrhosis is a challenge because it is situated at the crossroads between the liver, the metabolic, and the cardiovascular diseases. Therefore, the therapeutic interventions should not only target the liver but also the associated cardiometabolic conditions and should be adapted accordingly. The objective of the current review is to critically discuss the particularities in the management of patients with NAFLD-related cirrhosis. We relied on the recommendations of scientific societies and discussed them in the specific context of NAFLD cirrhosis and the surrounding cardiometabolic milieu. Herein, we covered the following aspects: (1) the weight loss strategies through lifestyle interventions to avoid sarcopenia and improve portal hypertension; (2) the optimal control of metabolic comorbidities in particular type 2 diabetes aimed not only to improve cardiovascular morbidity/mortality but also to lower the incidence of cirrhosis-related complications (we discussed various aspects related to the safety of oral antidiabetic drugs in cirrhosis); (3) the challenges in performing bariatric surgery in patients with cirrhosis related to the portal hypertension and the risk of cirrhosis decompensation; (4) the particularities in the diagnosis and management of the portal hypertension and the difficulties in managing patients awaiting for liver transplantation; and (5) the difficulties in developing drugs and conducting clinical trials in patients with NAFLD-related cirrhosis. Moreover, we discussed the emerging options to overcome these obstacles.

Type 2 diabetes mellitus (T2DM) is linked to a heightened likelihood of experiencing fractures. It is crucial to ascertain whether medications used to lower blood sugar levels can elevate the risk of fractures. We aimed to investigate and compare the effects of glucagon-like peptide 1 receptor agonists (GLP-1RA), Dipeptidyl Peptidase-4 Inhibitors (DPP-4i), and Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) on the fracture risk in patients with T2D in the real world.

A network meta-analysis conducted an inclusive literature search in PubMed, Scopus, Web of Science, and Cochrane Library to select appropriate population-based cohort studies that investigated the risk of bone fractures of (GLP-1RA), (DPP-4i) or (SGLT-2i) in the real world. A network meta-analysis (NMA) was performed using R software to investigate the risk of total fractures as a primary outcome among patients who used (GLP-1RAs), (SGLT-2i) or (DPP-4i) versus each other or other glucose-lowering medications (GLMs). The odds ratio (OR) and 95% confidence interval (CI) were summarized overall network and for each pairwise direct and indirect comparison. The surface under the cumulative ranking curve (SUCRA) with the P-scores was calculated for each treatment in the network meta-analysis to detect their cumulative ranking probabilities in lowering the risk of total fractures.

In our NMA, we identified a set of 13 population-based cohort studies comprising a total of 1,064,952 patients. The risk of fracture was identified with the follow-up duration for each class. We found a significant decrease in the fracture risk by about 87% associated with patients who used SGLT2 inhibitors in combination with other glucose-lowering medications, followed by SGLT2 inhibitors alone by about 67%, then GLP-1 receptor agonists by about 60%, and at last DPP-4 inhibitors by about 55%.

Our study's collective findings suggest a significant association of the low risk of fracture with the use of SGLT2i with other GLMs combination, SGLT2i alone, GLP-1RA, and DPP-4i, respectively. This population-based analysis offers the best available evidence and might be helpful for clinicians in the decision of the most suitable T2DM treatment strategies, especially for elderly type 2 diabetic patients, as they may be safe in terms of fracture.

https://www.crd.york.ac.uk/prospero/, identifier CRD42023448720.

To compare 13-year mortality rates in normoglycemic, prediabetic and diabetic subjects attending a community-based screening and intervention programme.

Population survey identified 2569 cardiovascular disease (CVD) white risk subjects aged 45-70 years and without manifested CVD or diabetes. Oral glucose tolerance test was performed, and multifactorial intervention was provided. Effect of glycemic status on mortality was estimated in models adjusted for age, gender, education years, smoking, body mass index, mean arterial pressure, total cholesterol, and physical activity.

Of the subjects, 2055 (77 %) were normoglycemic, 380 (14 %) had prediabetes and 224 (9 %) diabetes. Compared to the normoglycemic group, the fully adjusted hazard ratios (HR) for all-cause mortality were 1.34 (95 % CI: 0.98-1.83) in the prediabetes group and 2.31 (95 % CI: 1.62-3.31) in the diabetes group. Standardized mortality rates were 0.63 (95 % CI: 0.54-0.73), 0.91 (95 % CI: 0.69-1.18), and 1.55 (95 % CI: 1.19-2.02) in the normoglycemic, prediabetes, and diabetes groups, respectively. The most common cause of death was cancer (42 % of all deaths), followed by CVD (28 %).

Screen-detected diabetes carries a substantial risk of death even after primary care intervention. The pattern of excess mortality has shifted towards cancer deaths.

The management of type 2 diabetes mellitus patients has changed over the past decade, and a large number of antidiabetic drug treatment options are now available. This complexity poses challenges for healthcare professionals and may result in potentially inappropriate prescriptions of antidiabetic drugs in patients with type 2 diabetes mellitus which can be limited using screening tools. The effectiveness of explicit tools such as lists of potentially inappropriate prescriptions has been widely demonstrated. The aim was to set up nominal groups of healthcare professionals from several disciplines and develop a list of explicit definition of potentially inappropriate prescriptions of antidiabetic drugs.

In a qualitative, nominal-groups approach, 30 diabetologists, general practitioners, and pharmacists in France developed explicit definitions of potentially inappropriate prescriptions of antidiabetic drugs in patients with type 2 diabetes mellitus. A nominal group technique is a structured method that encourages all the participants to contribute and makes it easier to reach an agreement quickly. Each meeting lasted for two hours.

The three nominal groups comprised 14 pharmacists, 10 diabetologists, and 6 general practitioners and generated 89 explicit definitions. These definitions were subsequently merged and validated by the steering committee and nominal group participants, resulting in 38 validated explicit definitions of potentially inappropriate prescriptions of antidiabetic drugs. The definitions encompassed four contexts: (i) the temporary discontinuation of a medication during acute illness (n = 9; 24%), (ii) dose level adjustments (n = 23; 60%), (iii) inappropriate treatment initiation (n = 3; 8%), and (iv) the need for further monitoring in the management of type 2 diabetes mellitus (n = 3; 8%).

The results of our qualitative study show that it is possible to develop a specific list of explicit definitions of potentially inappropriate prescriptions of antidiabetic drugs in patients with type 2 diabetes mellitus by gathering the opinions of healthcare professionals caring for these patients. This list of 38 explicit definitions necessitates additional confirmation by expert consensus before use in clinical practice.

To investigate clinical outcomes in adults with type 2 diabetes (T2D) after insulin degludec/insulin aspart (IDegAsp) treatment in a real-world setting.

The 26 weeks study involved 1102 adults with T2D who were either initiated with or switched to IDegAsp according to local practice in six countries. It was an open-label, non-interventional study. The primary endpoint was the change in glycosylated haemoglobin (HbA1c) levels from baseline to the end of study (EOS).

From India, 185 adults participated in this study with mean age of 58.1 (10.3) years and 14.4 (8.1) years of mean duration of T2D. Mean HbA1c decreased from 9.8% (1.8) at baseline to 8.2% (0.1) at the EOS; change in HbA1c from baseline [95% CI]: -1.6% (0.1) [-1.8; -1.4], P < 0.0001. There was a significant reduction in mean fasting plasma glucose (FPG) level from 190.0 (65.8) mg/dl at baseline to 141.9 (4.3) mg/dl at EOS; change in FPG from baseline [95% CI]: -52.2 (4.3) mg/dl [-60.7; -43.7], P < 0.0001. There was a numerical reduction in resource utilization related to diabetes and its complications and hypoglycaemic episodes. From baseline to EOS, the participants with outpatient visits (72 to 32) and workdays missed (2 to 0) decreased. Additionally, the number of patient-reported non-severe hypoglycaemic (47 to 8) and severe hypoglycaemic (4 to 1) episodes decreased as well.

Initiation or switching to IDegAsp led to improvement in glycaemic control in real-world population of Indian adults with T2D. This was accompanied by a numerical reduction in resource utilization and patient-reported hypoglycaemia. Clinical trial registration: NCT04042441.

The sodium-glucose co-transporter 2 (SGLT2) inhibitors are FDA-approved class of drugs for diabetes management. They improve glycemic control by inducing glucosuria. Notwithstanding with potent anti-hyperglycemic activity, SGLT2 inhibitors are emerging as drugs with multifaceted therapeutic potential, evidenced for cardioprotective, renoprotective, antihypertensive, and neuroprotective activities. Continuous attempts are being accomplished through structural modification, development of new formulation, or combination with other drugs, to enhance the bioactivity spectrum of SGLT2 inhibitors for better management of diabetes and related complications.

This review comprises a summary of patent applications, acquired using the Espacenet Patent Search database, concerning SGLT2 inhibitors from 2019 to 2023, with focus on improving therapeutic potentials in management of diabetes and metabolic complications.

SGLT2 inhibitors have provided an exciting treatment option for diabetes. Originally developed as anti-hyperglycemic agents, SGLT2 inhibitors exert pleiotropic metabolic responses and have emerged as promising antidiabetic agents with cardio-protective and reno-protective activities. Given their distinct therapeutic profile, SGLT2 inhibitors have revolutionized the management of diabetes and associated complications. Emerging evidences on their therapeutic potential against cancer, male reproductive dysfunctions, and neurodegenerative diseases indicate that further research in this field may unfold novel prospective on their plausible use in the management of other chronic conditions.

Finerenone was approved for the treatment of type 2 diabetes patients with chronic kidney disease. However, the post-marketing safety of finerenone in the real world is unknown.

The quarterly reported data related to finerenone from the third quarter of 2021 to the second quarter of 2023 were collected by using the FAERS database. Two disproportionality analysis methods were estimated by using Reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN).

A total of 1067 adverse events (AEs) were included. Twenty-four kinds of system organ classes (SOCs) were classified for the organs and systems involved and 39 AEs with significant safety signals were identified using ROR and BCPNN at the preferred terms (PTs) level. Most AEs originated from the United States, and the median time to onset of AEs was 13 days. Three hundred and fifty-one (55.5%) reported serious outcome. The proportion of medication combinations was 29.0%. The most commonly reported AEs were the glomerular filtration rate decreased. Safety signals have also been observed in new and unexpected AEs.

The analysis of the AE signals may contribute to minimizing the risks associated with its use.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a novel class of incretin mimetics for treating type 2 diabetes (T2D). This study evaluated the impact of semaglutide, the first oral GLP-1RA, on glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and body composition and anthropometric parameters. Additionally, the effects on cardiovascular risk factors and quality of life (QoL) in T2D patients were assessed. Methods: A prospective observational study with a six-month follow-up was conducted. Clinical parameters, including HbA1c, FPG, anthropometric measurements, blood pressure, cardiovascular risk factors, Diabetes Treatment Satisfaction Questionnaire (DTSQ) responses, and Short Form (36) Health Survey (SF-36) responses, were collected at baseline (T0) and at six months (T1). Results: Sixty-one subjects were enrolled, with there being an average T2D duration of 4.67 ± 3.93 years. Significant decreases were observed in HbA1c (µ = -1.24; SD = 1.33; p < 0.05), FPG (µ = -31.01 mg/dL; SD = 41.71; p < 0.05), body composition and anthropometric parameters (p < 0.05), and cardiovascular risk factors (p < 0.05), with an increase in DTSQ scores (p < 0.05). Conclusions: The administration of 14 mg/day oral semaglutide improved several clinical parameters after six months of treatment. These findings suggest semaglutide is effective in improving glycemic control, weight management, and some cardiovascular risk factors in T2D patients.

New anti-diabetic medications, including glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 (SGLT2) inhibitors are recommended in guidelines to reduce cardio-renal events in type 2 diabetes mellitus (T2DM), independent of glucose control. Yet they might be underused in real world. This study aims to address the knowledge gap, prescription patterns and barriers faced by Chinese doctors. Cardio-Metabolic Survey was a cross-sectional study conducted among doctors managing diabetic patients in clinical practice, via a designated online questionnaire from May 1st, to Dec. 31th, 2022. A total of 358 doctors from 57 hospitals across Beijing participated in this survey, 34.9% from tertiary hospitals. Only 30-40% doctors demonstrated somewhat understanding of the mechanism and clinical applications of GLP-1RA or SGLT2 inhibitors. There is no difference in understanding of these two medications overall (p = 0.336). However, doctors in tertiary hospitals have a higher understanding of GLP-1RA and SGLT2 inhibitors compared to those in non-tertiary hospitals (p = 0.049, and 0.008, respectively). 40.2% doctors have never prescribed GLP-1RA, and 36.6% for SGLT2 inhibitors. The frequency of prescribing SGLT2 inhibitors was significantly higher than prescribing GLP-1RA (p = 0.005). The main barriers on prescription include high cost, poor adherence, side effects concern, and insufficient knowledge about these medications. Chinese doctors currently have limited understanding and low prescription frequency for GLP-1RA and SGLT2 inhibitors. Multifaceted approaches are needed to improve doctors' knowledge and strengthen their ability to manage T2DM effectively.

The increasing burden of type 2 diabetes (T2D), in relation to alarming rise in the prevalence; challenges in the diagnosis, prevention, and treatment; as well as the substantial impact of disease on longevity and quality of life, is a major concern in healthcare worldwide. Sulfonylureas (SUs) have been a cornerstone of T2D pharmacotherapy for over 60 years as oral antidiabetic drugs (OADs), while the newer generation SUs, such as gliclazide modified release (MR), are known to be associated with low risk of hypoglycemia in addition to the cardiovascular neutrality. This scoping review aimed to specifically address the current position of gliclazide MR among other SUs in the contemporary treatment paradigm for T2D and to provide a practical guidance document to assist clinicians in using gliclazide MR in real-life clinical practice. The main topics addressed in this paper include the role of early and sustained glycemic control and use of SUs in T2D management, the properties of gliclazide MR in relation to its effectiveness and safety, the use of gliclazide therapy in special populations, and the place of SUs as a class and gliclazide MR specifically in the current T2D treatment algorithm.

Add-on of basal insulin (BI) to intensify the ongoing therapy with glucagon-like peptide 1 receptor agonist (GLP-1 RA) is recommended, but it is unclear if free or fixed combination of BI and GLP-1 RA produce similar outcomes. A retrospective comparative effectiveness analysis of the add-on of glargine 300 U/mL (Gla-300) to ongoing GLP-1 RA vs. switch to fixed ratio combination of degludec and liraglutide (iDegLira) was performed.

Real-world data collected in electronic medical records by 32 Italian diabetes clinics. Propensity score (PS) adjustment was applied to assess changes in glycated hemoglobin (HbA1c), fasting blood glucose (FBG), body weight, and BI dose after 6 months from Gla-300 or iDegLira initiation. Compared to iDegLira group (N = 260), Gla-300+GLP-1 RA group (N = 255) had older age and higher levels of HbA1c (9.1 vs. 8.9%). After 6 months, statistically significant greater FBG improvement [estimated mean difference and 95% confidence intervals: -24.05 mg/dl (-37.04; -11.06; p = 0.0003) and BI dose increase [+0.03 U/kg (95%CI 0.00; 0.06); p = 0.009] were found in the free vs. fixed combination group, although low doses of BI (0.2 U/kg) were reached in both groups. Trends of larger HbA1c and body weight reductions with the free combination were also found, without reaching the statistical significance.

Although inertia in insulin initiation and titration was documented in both groups, higher benefit on FBG control was obtained with free vs. fixed combination, likely due to a better titration of BI and GLP-1 RA.

A previous study showed that high-glucose (HG) conditions induce mitochondria fragmentation through the calcium-mediated activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) in H9C2 cells. This study tested whether empagliflozin could prevent HG-induced mitochondria fragmentation through this pathway. We found that exposing H9C2 cells to an HG concentration decreased cell viability and increased cell apoptosis and caspase-3. Empagliflozin could reverse the apoptosis effect of HG stimulation on H9C2 cells. In addition, the HG condition caused mitochondria fragmentation, which was reduced by empagliflozin. The expression of mitochondria fission protein was upregulated, and fusion proteins were downregulated under HG stimulation. The expression of fission proteins was decreased under empagliflozin treatment. Increased calcium accumulation was observed under the HG condition, which was decreased by empagliflozin. The increased expression of ERK 1/2 under HG stimulation was also reversed by empagliflozin. Our study shows that empagliflozin could reverse the HG condition, causing a calcium-dependent activation of the ERK 1/2 pathway, which caused mitochondria fragmentation in H9C2 cells.

Subcutaneous once-weekly (ow) semaglutide is a recent treatment option for type 2 diabetes (T2D) and obesity, but real-world data on weight loss and associated changes in body composition, nutrients intake, and quality of life are still scarce. This observational, prospective clinical study involved all T2D patients starting ow semaglutide according to routine care between December 2021 and February 2022. Clinical information was collected after 6 months (T6) and 12 months (T12) from semaglutide initiation (T0). Bioelectrical Impedance Analysis (BIA) was performed to measure changes in body composition. Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the 36 - items Short Form Health Survey (SF-36) were administered as patient-reported outcomes (PROs). Changes in continuous endpoints (weight, body composition, nutrients intake, other clinical parameters, and PROs) were assessed using mixed models for repeated measurements. Overall, 90 patients (age 63.0 ± 10.0 years; diabetes duration 7.6 ± 5.9 years; 58.9% men; HbA1c 7.7 ± 1.1%; weight 95.4 ± 19.4 Kg, BMI 34.6 ± 6.4 Kg/m2; 36.7% naïve to diabetes treatment, 43.3% on metformin, 10.0% on dual oral therapy, and 10.0% treated with schemes including insulin) were included in the study. After 6 months from semaglutide initiation, body weight significantly decrease by -4.69 Kg (95%CI -6.19;-3.19) (primary endpoint). After 12 months, body weight was further reduced (-5.38 Kg; 95%CI -7.79;-2.97). At BIA, fat mass was significantly reduced by 2.1 Kg after 6 months but only slightly reduced after 12 months vs. baseline; lean mass was also significantly reduced by over 3 Kg both at 6 and 12 months. Intake of all nutrients declined in the first 6 months of therapy, although only lipids reduction reached the statistical significance (-6.73 g; p=0.02). Statistically significant improvements in BMI, waist circumference, glycemic control, blood pressure and lipid profile were documented. Satisfaction with treatment (DTSQ questionnaire) and mental health (MCS score of SF-36 questionnaire) significantly increased during the follow-up. The study documented real-world benefits of semaglutide for treating obesity in T2D subjects, with important changes on clinical and patient-reported outcomes. Loss of lean mass associated with weight loss warrants attention; parallel strategies to preserve skeletal muscle and improve physical function, i.e. nutritional education and structured exercise, are of great importance.

Although continuous glucose monitoring (CGM) devices are now considered the standard of care for people with type 1 diabetes mellitus, the uptake among people with type 2 diabetes mellitus (T2DM) has been slower and is focused on those receiving intensive insulin therapy. However, increasing evidence now supports the inclusion of CGM in the routine care of people with T2DM who are on basal insulin-only regimens or are managed with other medications. Expanding CGM to these groups could minimize hypoglycaemia while allowing efficient adaptation and escalation of therapies. Increasing evidence from randomized controlled trials and observational studies indicates that CGM is of clinical value in people with T2DM on non-intensive treatment regimens. If further studies confirm this finding, CGM could soon become a part of routine care for T2DM. In this Perspective we explore the potential benefits of widening the application of CGM in T2DM, along with the challenges that must be overcome for the evidence-based benefits of this technology to be delivered for all people with T2DM.

The development of steatotic liver disease after liver transplant (LT) is widely described, and epidemiological data have revealed an increased incidence in recent times. Its evolution runs from simple steatosis to steatohepatitis and, in a small proportion of patients, to significant fibrosis and cirrhosis. Apparently, post-LT steatotic disease has no impact on the recipient's overall survival; however, a higher cardiovascular and malignancy burden has been reported. Many donors' and recipients' risk factors have been associated with this occurrence, although the recipient-related ones seem of greater impact. Particularly, pre- and post-LT metabolic alterations are strictly associated with steatotic graft disease, sharing common pathophysiologic mechanisms that converge on insulin resistance. Other relevant risk factors include genetic variants, sex, age, baseline liver diseases, and immunosuppressive drugs. Diagnostic evaluation relies on liver biopsy, although non-invasive methods are being increasingly used to detect and monitor both steatosis and fibrosis stages. Management requires a multifaceted approach focusing on lifestyle modifications, the optimization of immunosuppressive therapy, and the management of metabolic complications. This review aims to synthesize the current knowledge of post-LT steatotic liver disease, focusing on the recent definition of metabolic-dysfunction-associated steatotic liver disease (MASLD) and its metabolic and multisystemic concerns.

This scoping review prepared by endocrinology and nephrology experts aimed to address the significance of finerenone, as a novel therapeutic option, in diabetic kidney disease (DKD), based on the biological prospect of cardiorenal benefit due to non-steroidal mineralocorticoid receptor antagonist (MRA) properties, and the recent evidence from the finerenone phase 3 program clinical trials. The importance of finerenone in slowing DKD progression was critically reviewed in relation to the role of MR overactivation in the pathogenesis of cardiorenal disease and unmet needs in the current practice patterns. The efficacy and safety outcomes of finerenone phase III study program including FIDELIO-DKD, FIGARO-DKD and FIDELITY were presented. Specifically, perspectives on inclusion of patients with preserved estimated glomerular filtration rate (eGFR) or high albuminuria, concomitant use of sodium-glucose co-transporter-2 inhibitor (SGLT2i) or glucagon-like peptide 1 receptor agonist (GLP-1 RA), baseline glycated hemoglobin (HbA1c) level and insulin treatment, clinically meaningful heart failure outcomes and treatment-induced hyperkalemia were addressed. Finerenone has emerged as a new therapeutic agent that slows DKD progression, reduces albuminuria and risk of cardiovascular complications, regardless of the baseline HbA1c levels and concomitant treatments (SGLT2i, GLP-1 RA, or insulin) and with a favorable benefit-risk profile. The evolving data on the benefit of SGLT2is and non-steroidal MRAs in slowing or reducing cardiorenal risk seem to provide the opportunity to use these pillars of therapy in the management of DKD, after a long-period of treatment scarcity in this field. Along with recognition of the albuminuria as a powerful marker to detect those patients at high risk of cardiorenal disease, these important developments would likely to impact standard-of-care options in the setting of DKD.

Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease and affects approximately 40% of individuals with diabetes . Cases of DKD continue to rise globally as the prevalence of diabetes mellitus increases, with an estimated 415 million people living with diabetes in 2015 and a projected 642 million by 2040. DKD is associated with significant morbidity and mortality, representing 34% and 36% of all chronic kidney disease deaths in men and women, respectively. Common comorbidities including hypertension and ageing-related nephron loss further complicate disease diagnosis and progression. The progression of DKD involves several mechanisms including glomerular endothelial cell dysfunction, inflammation, and fibrosis. Targeting these mechanisms has formed the basis of several therapeutic agents. Renin-angiotensin-aldosterone system (RAAS) blockers, specifically angiotensin receptor blockers (ARBs), demonstrate significant reductions in macroalbuminuria. Sodium-glucose transporter type 2 (SGLT-2) inhibitors demonstrate kidney protection independent of diabetes control while also decreasing the incidence of cardiovascular events. Emerging agents including glucagon-like peptide 1 (GLP-1) agonists, anti-inflammatory agents like bardoxolone, and mineralocorticoid receptor antagonists show promise in mitigating DKD progression. Many novel therapies including monoclonal antibodies CSL346, lixudebart, and tozorakimab; mesenchymal stem/stromal cell infusion; and cannabinoid-1 receptor inverse agonism via INV-202 are currently in clinical trials and present opportunities for further drug development.

Observational studies have found a potential link between the use of thiazolidinediones (TZDs) and a lower risk of Alzheimer's disease (AD) development. Platelets were the great source of amyloid-β (Aβ) and involved in the development of AD. This study aimed to assess the correlation between antidiabetic agents and platelet characteristics, hoping to provide a potential mechanism of TZDs neuroprotection in AD.

Drug-targeted Mendelian randomization (MR) was performed to systematically illustrate the long-term effects of antidiabetic agents on platelet characteristics. Four antidiabetic agent targets were considered. Positive control analysis for type 2 diabetes (T2D) was conducted to validate the selection of instrumental variables (IVs). Colocalization analysis was used to further strengthen the robustness of the results.

Positive control analysis showed an association of four antidiabetic agents with lower risk of T2D, which was consistent with their mechanisms of action and previous evidence from clinical trials. Genetically proxied TZDs were associated with lower platelet count (β[IRNT] = -0.410 [95 % CI -0.533 to -0.288], P = 5.32E-11) and a lower plateletcrit (β[IRNT] = -0.344 [95 % CI -0.481 to -0.206], P = 1.04E-6). Colocalization suggested the posterior probability of hypothesis 4 (PPH4) > 0.8, which further strengthened the MR results.

Genetically proxied TZDs were causally associated with lower platelet characteristics, particularly platelet count and plateletcrit, providing insight into the involvement of platelet-related pathways in the neuroprotection of TZDs against AD. Future studies are warranted to reveal the underlying molecular mechanism of TZDs' neuroprotective effects through platelet pathways.

Measurement of urine albumin is critical for diagnosis, risk classification, and monitoring of chronic kidney disease (CKD). Guidelines recommend clinical decision cutoffs for the urine albumin-to-creatinine ratio (ACR) of 30 and 300 mg/g (3 and 30 mg/mmol). However, differences among manufacturers' routine urine albumin measurement procedures have been found to exceed 40%, suggesting CKD diagnosis and risk classification may vary depending upon the specific measurement procedure implemented in the laboratory.

This review discusses urine albumin pathophysiology and clinical practice guideline recommendations for CKD. The review also provides recommendations for urine specimen collection and storage, and results reporting for the ACR. Recent advances in measurement techniques and development of reference systems intended to facilitate standardization of urine albumin measurements are reviewed.

Urine albumin is an important measurement procedure used for diagnosis, risk classification, and management of CKD. Urine albumin results should be reported as the ACR using quantitative measurement procedures. Random urine collections used for albuminuria screening should be followed by confirmation with first morning void collections to reduce variation and increase diagnostic accuracy for urine albumin measurement. Most measurement procedures utilize immunoturbidimetric or immunonephelometric techniques. However, results vary significantly among measurement procedures, potentially resulting in differences in classification or risk assessment for CKD. The National Institute for Standards and Technology (NIST) and other laboratories are developing reference systems, including liquid chromatography-tandem mass spectrometry candidate reference measurement procedures and reference materials, to enable standardization of routine measurement procedures.

To estimate the proportion of individuals with established Type 2 Diabetes Mellitus (T2DM) and Cardiovascular Disease (CVD) who are receiving pharmacological anti-diabetic treatment with evidence of cardiovascular benefit at a hospital in Argentina.

Cross-sectional study conducted at the Italian Hospital of Buenos Aires. A consecutive sample of adult patients affiliated with the institutional prepaid health plan active in March 2020, diagnosed with T2DM and established CVD, was included. Data were collected from the Electronic Health Record. The proportion of pharmacological adequacy (combined use of metformin plus sodium-glucose co-transporter 2 inhibitors and/or glucagon-like peptide 1 receptor agonists) was reported along with its respective 95% confidence interval (CI).

A total of 1539 patients were included, with a mean age of 76.2 years; 65.3% were male, and 81.6% were overweight or obese. Hemoglobin A1c levels were recorded in the past year for 74.9% of patients, with an average value of 6.9% (SD 1.2). The most prescribed drugs were metformin (61.3%), insulin (26.7%), and gliptins (11%). Out of the total included patients, 82 exhibited pharmacotherapeutic adequacy for diabetes treatment, with a prevalence of 5.3% (95% CI 4.2-6.5).

The prevalence of prescribing anti-diabetic drugs with evidence of cardiovascular benefit was 5.3% (95% CI 4.2-6.5). This real-world evidence highlights the low frequency of prescribing this type of medication at the time of the study in a high cardiovascular risk population.

To estimate the contemporary prevalence of established cardiovascular disease (CVD) in adults with type 2 diabetes (T2D) in Mexico.

CAPTURE was a multinational, non-interventional, cross-sectional study across 13 countries from five continents. Standardized demographic and clinical data were collected from adults with T2D attending a single routine healthcare visit in primary or specialized care between December 2018 and September 2019. Data from Mexico are analyzed in this study.

Of the 9,823 patients included in the CAPTURE study, 820 (8.3%) participants were from Mexico, mainly attended in private centers (29.3% in 6 specialized diabetes treatment centers and 70.7% in 26 primary care centers). The median age was 63.0 years, 52.6% were women, the duration of diabetes was 11.8 years and the average HbA1c 7.5%. The weighted prevalence [95% CI] of CVD and atherosclerotic CVD was 36.9% [34.1-39.6] and 29.5% [26.7-32.3], respectively. Additionally, the prevalence of coronary heart disease, heart failure, peripheral arterial disease and cerebrovascular disease was 23.1% [20.6-25-7], 8.4% [6.8-10.0], 5.0% [3.5-6.5] and 3.9% [2.6-5.2], respectively. Glucose lowering drugs were used in 88.5% of patients, being metformin the most commonly drug used (79.4%), followed by sulfonylureas (26.3%). SGLT-2 inhibitors and GLP1 receptor agonists were used in 15.5% and 3.9%, respectively.

In Mexico, nearly four out of ten patients with T2D mainly attended in private centers have CVD, particularly atherosclerotic CVD. Most patients were not taking glucose lowering drugs with proven CV benefit.

To assess intensification approaches with basal insulin (BI) following glucagon-like peptide-1 receptor agonist (GLP-1 RA) treatment in type 2 diabetes (T2D).

Real-world data were collected in electronic medical records by 32 Italian diabetes clinics between 2011 and 2021. Primary endpoint was the proportion of insulin-naïve T2D patients treated with GLP-1 RA who initiated (add-on or switch) BI. Secondary endpoints were: treatment approaches, mean time to BI start, effectiveness and safety. Among 7,962 eligible patients, BI was prescribed to 3,164 (39.7%; 95%CI 38.7; 40.8): 67.6% switched to BI (22.1% also starting 1-3 injections of short-acting insulin), 22.7% added BI while maintaining GLP-1 RA, and 9.7% switched to a fixed-ratio combination of GLP-1 RA and BI (FRC). Median time since the first GLP-1 RA to BI/FRC prescription was 27.4 (IQ range 11.8-53.5) months. In this study 60.3% of patients did not start BI/FRC, among whom 15.2% intensified GLP-1 RA therapy with other oral agents. Effectiveness and safety were documented in all intensification approaches with BI/FRC, but HbA1c level at intensification time of ≥9.0% and suboptimal BI titration suggested clinical inertia. Use of second generation BI and add-on to GLP-1 RA schemes increased over time and effectiveness improved.

Clinical inertia should be overcome using innovative insulin options. Timely combination therapy of BI and GLP-1 RA is a valuable choice.

This study developed a simple algorithm based on clinical results described in medical literature and which allows one to simplify complex insulin regimes with IdegLira to avoid adverse events related to the complexity of some insulin treatments.

We conducted a systematic review of the literature that allowed us to identify studies that evaluated the clinical result of simplifying complex insulin regimes. The authors reviewed the common factors these simpler regimes had, including the type of patients who used them.

We found nine clinical studies published between 2017 and 2022, eight performed in Europe and one in Latin America. The monitoring time of the studies ranged between 3 and 18 months. The size of the study populations was between 61 and 611 patients (the latter was in five countries). In all studies, HbA1c decreased by 0.6-1.7% and the weight decreased by 0.1-3.11 kg.

On the basis of the findings of these studies, we made some recommendations for clinical practice to simplify treatment. The results of these studies support an algorithm that simplifies the treatment of complex insulin regimens.

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease that affects more than a quarter of the global population and whose prevalence is increasing worldwide due to the pandemic of obesity. Obesity, impaired glucose metabolism, high blood pressure and atherogenic dyslipidemia are risk factors for MASLD. Therefore, insulin resistance may be closely associated with the development and progression of MASLD. Hepatic entry of increased fatty acids released from adipose tissue, increase in fatty acid synthesis and reduced fatty acid oxidation in the liver and hepatic overproduction of triglyceride-rich lipoproteins may induce the development of MASLD. Since insulin resistance also induces atherosclerosis, the leading cause for death in MASLD patients is cardiovascular disease. Considering that the development of cardiovascular diseases determines the prognosis of MASLD patients, the therapeutic interventions for MASLD should reduce body weight and improve coronary risk factors, in addition to an improving in liver function. Lifestyle modifications, such as improved diet and increased exercise, and surgical interventions, such as bariatric surgery and intragastric balloons, have shown to improve MASLD by reducing body weight. Sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to improve coronary risk factors and to suppress the occurrence of cardiovascular diseases. Both SGLT2i and GLP-1 have been reported to improve liver enzymes, hepatic steatosis and fibrosis. We recently reported that the selective peroxisome proliferator-activated receptor-alpha (PPARα) modulator pemafibrate improved liver function. PPARα agonists have multiple anti-atherogenic properties. Here, we consider the pathophysiology of MASLD and the mechanisms of action of such drugs and whether such drugs and the combination therapy of such drugs could be the treatments for MASLD.

The incidence of morbidity and mortality in patients with type 2 diabetes mellitus is substantially correlated with cardiovascular disease and chronic kidney disease. The current guidelines recommend the use of renin-angiotensin system blockers, but recent studies probed into the effects of finerenone to mitigate the risk of cardiorenal events. This meta-analysis was performed to demonstrate the effects of finerenone on cardiorenal events, comprising cardiovascular mortality, heart failure, change in estimated glomerular filtration rate, and serum potassium levels.

After screening with our eligibility criteria, 350 articles were identified with an initial literature search on multiple databases, including PubMed, Science Direct, and Cochrane Central. Seven randomized controlled trials with a total of 15 462 patients (n=8487 in the finerenone group; n=6975 in the control group) were included.

Patients receiving finerenone were at a reduced risk for cardiovascular mortality [HR: 0.84 (0.74, 0.95)], heart failure [OR: 0.79 (0.68, 0.92)], decrease in estimated glomerular filtration rate by 40% [OR: 0.82 (0.74, 0.91)] and by 57% [OR: 0.70 (0.59, 0.82)]; and a higher incidence of moderate hyperkalemia [OR: 2.25 (1.78, 2.84)].

Finerenone, owing to its better mineralocorticoid affinity, and a much lower risk of adverse effects, promises to be a much better alternative than other renin-angiotensin system blockers available for the treatment of chronic kidney disease patients with type 2 diabetes. Further trials should be conducted to provide more definitive evidence to assess the safety and efficacy of finerenone compared to spironolactone and eplerenone.

The current document has been developed by the Liver Forum who mandated the NAFLD-Associated Comorbidities Working Group - a multistakeholder group comprised of experts from academic medicine, industry and patient associations - to identify aspects of diverse comorbidities frequently associated with non-alcoholic steatohepatitis (NASH) that can interfere with the conduct of therapeutic trials and, in particular, impact efficacy and safety results. The objective of this paper is to propose guidance for the management of relevant comorbidities in both candidates and actual participants in NASH therapeutic trials. We relied on specific guidelines from scientific societies, when available, but adapted them to the particulars of NASH trials with the aim of addressing multiple interacting requirements such as maintaining patient safety, reaching holistic therapeutic objectives, minimising confounding effects on efficacy and safety of investigational agents and allowing for trial completion. We divided the field of action into: first, analysis and stabilisation of the patient's condition before inclusion in the trial and, second, management of comorbidities during trial conduct. For the former, we discussed the concept of acceptable vs. optimal control of comorbidities, defined metabolic and ponderal stability prior to randomisation and weighed the pros and cons of a run-in period. For the latter, we analysed non-hepatological comorbid conditions for changes or acute events possibly occurring during the trial, including changes in alcohol consumption, in order to detail when specific interventions are necessary and how best to manage concomitant drug intake in line with methodological constraints. These recommendations are intended to act as a guide for clinical trialists and are open to further refinement when additional data become available.