Comparative renal outcomes of matched cohorts of patients with type 2 diabetes receiving SGLT2 inhibitors or GLP-1 receptor agonists under routine care.

AIMS/HYPOTHESIS: We compared the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) on renal outcomes in individuals with type 2 diabetes, focusing on the changes in eGFR and albuminuria. METHODS: This was a multicentre retrospective observational study on new users of diabetes medications. Participant characteristics were assessed before and after propensity score matching. The primary endpoint, change in eGFR, was analysed using mixed-effects models. Secondary endpoints included categorical eGFR-based outcomes and changes in albuminuria. Subgroup and sensitivity analyses were performed to assess robustness of the findings. RESULTS: After matching, 5701 participants/group were included. Participants were predominantly male, aged 61 years, with a 10 year duration of diabetes, a baseline HbA1c of 64 mmol/mol (8.0%) and BMI of 33 kg/m2. Chronic kidney disease (CKD) was present in 23% of participants. During a median of 2.1 years, from a baseline of 87 ml/min per 1.73 m2, eGFR remained higher in the SGLT2i group compared with the GLP-1RA group throughout the observation period by 1.2 ml/min per 1.73 m2. No differences were detected in albuminuria change. The SGLT2i group exhibited lower rates of worsening CKD class and favourable changes in BP compared with the GLP-1RA group, despite lesser HbA1c decline. SGLT2i also reduced eGFR decline better than GLP-1RA in participants without baseline CKD. CONCLUSIONS/INTERPRETATION: In individuals with type 2 diabetes, treatment with SGLT2i was associated with better preservation of renal function compared with GLP-1RA, as evidenced by slower decline in eGFR. These findings reinforce SGLT2i as preferred agents for renal protection in this patient population.

Oral Semaglutide in Routine Clinical Practice: Characteristics of People with Type 2 Diabetes Started on the Drug and Changes in Their Clinical Parameters after 24 Weeks of Treatment.

Background/Objectives: Semaglutide is the unique once-daily oral glucagon-like receptor agonist presently available. Aims of this study were to describe clinical characteristics of patients with type 2 diabetes (T2D) initiating oral semaglutide, to assess its effects on glycemic control, body weight (BW) and its tolerability in routine clinical practice. Methods: Electronic medical records from two Italian diabetes clinics were evaluated. Mean glycated hemoglobin (HbA1c) and BW were assessed in adults with T2D before and 6 months after oral semaglutide prescription. Treatment discontinuation and safety data were reported. Results: A total of 192 patients initiating oral semaglutide (44% female) presented a mean age of 66 years, a diabetes duration of 10 years, HbA1c of 7.9% and a BW of 82.6 kg. Almost 50% of patients were obese. Mean HbA1c and BW changes from baseline to follow up were -0.7% and -2.6 kg, respectively. Greater HbA1c reduction was observed in patients with baseline HbA1c ≥ 8% and with diabetes duration <5 years. The composite endpoint of HbA1c ≤7% and a weight loss ≥5% was achieved in 22.5% of the participants. A total of 40 patients (20.8%) discontinued treatment: 26 because of gastrointestinal adverse events, and 10 due to limited effectiveness in lowering HbA1c and/or BW. Conclusions: In a real clinical setting, patients initiating oral semaglutide showed suboptimal metabolic control, short diabetes duration and obesity; a significant improvement in HbA1c and BW was achieved mainly in patients with a more recent diabetes diagnosis, supporting the use of oral semaglutide in the early phase of the disease.

GLP1-GIP receptor co-agonists: a promising evolution in the treatment of type 2 diabetes.

Type 2 diabetes represents a growing challenge for global public health. Its prevalence is increasing worldwide, and, like obesity, it affects progressively younger populations compared to the past, with potentially greater impact on chronic complications. Dual glucagon like peptide 1 (GLP1) and glucose-dependent insulinotropic peptide (GIP) receptor agonists are among the new pharmacological strategies recently developed to address this challenge. Tirzepatide, characterized by its ability to selectively bind and activate receptors for the intestinal hormones GIP and GLP-1, has been tested in numerous clinical studies and is already currently authorized in several countries for the treatment of type 2 diabetes and obesity. In this context, the aim of the present document is to summarize, in the form of a narrative literature review, the currently available data on the main mechanisms of action of GIP/GLP-1 co-agonists and the clinical effects of tirzepatide evaluated in various clinical trials.

Comparing the effectiveness and cost-effectiveness of sulfonylureas and newer diabetes drugs as second-line therapy for patients with type 2 diabetes.

INTRODUCTION: We aimed to compare the effectiveness and cost-effectiveness profiles of glucagon-like peptide-1 receptor agonist (GLP-1-RA), sodium-glucose cotransporter 2 inhibitor (SGLT2i), and dipeptidyl peptidase-4 inhibitor (DPP-4i) compared with sulfonylureas and glinides (SU). RESEARCH DESIGN AND METHODS: Population-based retrospective cohort study based on linked regional healthcare utilization databases. The cohort included all residents in Lombardy aged ≥40 years, treated with metformin in 2014, who started a second-line treatment between 2015 and 2018 with SU, GLP-1-RA, SGLT2i, or DPP-4i. For each cohort member who started SU, one patient who began other second-line treatments was randomly selected and matched for sex, age, Multisource Comorbidity Score, and previous duration of metformin treatment. Cohort members were followed up until December 31, 2022. The association between second-line treatment and clinical outcomes was assessed using Cox proportional hazards models. The incremental cost-effectiveness ratios (ICERs) were calculated and compared between newer diabetes drugs and SU. RESULTS: Overall, 22 867 patients with diabetes were included in the cohort, among which 10 577, 8125, 2893 and 1272 started a second-line treatment with SU, DPP-4i, SGLT2i and GLP-1-RA, respectively. Among these, 1208 patients for each group were included in the matched cohort. As compared with SU, those treated with DPP-4i, SGLT2i and GLP-1-RA were associated to a risk reduction for hospitalization for major adverse cardiovascular events (MACE) of 22% (95% CI 3% to 37%), 29% (95% CI 12% to 44%) and 41% (95% CI 26% to 53%), respectively. The ICER values indicated an average gain of €96.2 and €75.7 each month free from MACE for patients on DPP-4i and SGLT2i, respectively. CONCLUSIONS: Newer diabetes drugs are more effective and cost-effective second-line options for the treatment of type 2 diabetes than SUs.

Liraglutide and not lifestyle intervention reduces soluble CD163 after comparable weight loss in obese participants with prediabetes or type 2 diabetes mellitus.

BACKGROUND: The GLP-1 receptor agonist liraglutide is used to treat hyperglycemia in type 2 diabetes but is also known to induce weight loss, preserve the beta cell and reduce cardiovascular risk. The mechanisms underlying these effects are however still not completely known. Herein we explore the effect of liraglutide on markers of immune cell activity in a population of obese individuals with prediabetes or newly diagnosed type 2 diabetes mellitus. METHOD: Plasma levels of the monocyte/macrophage markers, soluble (s)CD163 and sCD14, the neutrophil markers myeloperoxidase (MPO) and neutrophil gelatinase-associated lipocalin (NGAL),the T-cell markers sCD25 and T-cell immunoglobulin mucin domain-3 (sTIM-3) and the inflammatory marker TNF superfamily (TNFSF) member 14 (LIGHT/TNFSF14) were measured by enzyme-linked immunosorbent assays in obese individuals with prediabetes or diabetes diagnosed within the last 12 months, prior to and after comparable weight loss achieved with lifestyle changes (n = 20) or liraglutide treatment (n = 20), and in healthy subjects (n = 13). RESULTS: At baseline, plasma levels of the macrophage marker sCD163, and the inflammatory marker LIGHT were higher in cases as compared to controls. Plasma levels of sCD14, NGAL, sTIM-3 and sCD25 did not differ at baseline between patients and controls. After weight reduction following lifestyle intervention or liraglutide treatment, sCD163 decreased significantly in the liraglutide group vs. lifestyle (between-group difference p = 0.023, adjusted for visceral adipose tissue and triglycerides basal values). MPO and LIGHT decreased significantly only in the liraglutide group (between group difference not significant). Plasma levels of MPO and in particular sCD163 correlated with markers of metabolic dysfunction and inflammation. After weight loss, only sCD163 showed a trend for decreased levels during OGTT, both in the whole cohort as in those of liraglutide vs lifestyle group. CONCLUSION: Weight loss following treatment with liraglutide was associated with reduced circulating levels of sCD163 when compared to the same extent of weight loss after lifestyle changes. This might contribute to reduced cardiometabolic risk in individuals receiving treatment with liraglutide.

Oral or injectable semaglutide for the management of type 2 diabetes in routine care: A multicentre observational study comparing matched cohorts.

AIM: To investigate the real-world utilization and comparative clinical outcomes of injectable and oral semaglutide in individuals with type 2 diabetes (T2D) with the aim of enhancing understanding of the practical implications associated with choosing between these formulations. METHODS: New users of oral or injectable semaglutide were selected from a cohort of 14 079 initiators of glucagon-like peptide-1 receptor agonists. Propensity-score matching (PSM) was employed to create balanced groups, ensuring comparability. The analysis encompassed dose exposure, drug persistence, and clinical outcomes, including changes in glycated haemoglobin (HbA1c) and body weight, with up to 18 months' follow-up. RESULTS: We analysed two matched groups of 107 participants each, who comprised on average 63.6% men, aged 64 years, with diabetes duration of approximately 10 years, body mass index of 29 kg/m2 and HbA1c level of 7.7-7.8% (61-62 mmol/mol). The proportion of low, intermediate and high doses were similar with the oral and the injectable formulation. The change in HbA1c was similar between groups (-0.9% / -10 mmol/mol at 18 months) as was the proportion of individuals reaching HbA1c <6.5% (48 mmol/mol). The average change in body weight was similar in the two groups (-3.7 kg with injectable and -3.3 kg with oral at 18 months) but more new users of injectable semaglutide lost ≥5% body weight. Persistence on drug was longer with injectable than with oral semaglutide. CONCLUSION: In a real-world setting, improvements in HbA1c and body weight were similar after initiation of oral or injectable semaglutide. These results may be specific to the features of the matched cohorts under investigation, with limited generalizability to populations with different characteristics.

IDegLira for the real-world treatment of type 2 diabetes in Italy. Final results from the REX observational study.

AIM: The study was designed to generate real-world evidence on IDegLira in the Italian clinical practice in two groups of patients with type 2 diabetes (T2D), switching to IDegLira either from a basal only (basal group) or basal-bolus insulin regimen (BB group). MATERIALS AND METHODS: This was a non-interventional, multicentre, single-cohort, prospective study assessing the long-term glycaemic control in patients with T2D, who switched to IDegLira from a basal insulin ± glucose-lowering medication regimen with or without a bolus insulin component for approximately 18 months, conducted in 28 Italian diabetes centres. The primary endpoint was the change in glycated haemoglobin (HbA1c) levels from baseline to 6 months after IDegLira initiation. RESULTS: The study included 358 patients with a mean age 67.2 years and diabetes duration of 15.7 years. HbA1c significantly decreased from IDegLira start to all study time points in the overall population (basal group -1.19%; BB group -0.60% at the end of observation). Patients achieving HbA1c <7% levels increased from 12.9% (n = 43) to 40.3% (n = 110) at 18 months. Fasting blood glucose and body weight also significantly decreased in both groups, although more in the BB group. Overall, 14.3% of completed patients had an intensification of treatment (mainly in the basal group) and 48.6% had a simplification of treatment (mainly in the BB group). CONCLUSIONS: Switching to IDegLira in a real-world clinical setting is a valid therapeutic option for patients with T2D with inadequate glycaemic control on basal or BB insulin regimen and/or need to simplify their insulin therapy, with specific reasons and therapeutic goals according to different T2D management trajectories.

Non traumatic right Bochdalek hernia with loss of Domain in adults. Our experience and review of literature.

INTRODUCTION: Right-sided Bochdalek hernia (BH) is a rare developmental defect in the posterolateral diaphragm, allowing herniation of abdominal contents into the thorax. To date only 44 reported cases of right-sided BH have been surgically managed in adults in literature. We report one additional case of right-sided BH with loss of Domain. "Loss of domain" (LOD) is a term used commonly in the hernia literature to describe the distribution of abdominal content between the hernia and residual abdominopelvic cavity. After repairing hernias with significant LOD, serious physiological complications can arise. METHODS: PubMed and Cochrane bibliographical databases were searched (last search: February 2022) for studies concerning BH. CASE PRESENTATION: We report the case of a 50-year-old woman whose right-sided diaphragmatic hernia strangulated loops of small bowel and who was thus treated via urgent laparoscopy. After reduction of the intrathoracic contents we were unable to primarily close the midline fascia.We performed a staged abdominal wall reconstruction as the chronicity of the hernia led to loss of intra-abdominal domain. DISCUSSION: Bochdalek hernia (BH) is the most common type of congenital diaphragmatic hernia and is usually leftsided. It typically presents in neonates and diagnosis in adults is a rarity. Various surgical repair options include open surgery, laparoscopic repair, thoracoscopic approach and robotic transthoracic approaches. CONCLUSION: BH should be managed timely regardless of its symptoms to avoid future complications. The closure of the defect can be done by different methods. When, after diaphragmatic hernia repair, it is suspected that the herniated viscera have lost their domain, it is preferable to use a Temporary Abdominal Closure to prevent compartment syndrome. KEY WORDS: Bochdalek hernia with loss of Domain, Bochdalek hernia in adults, Non traumatic Bochdalek hernia, Right-sided diaphragmatic hernia.

Influenza vaccination for elderly, vulnerable and high-risk subjects: a narrative review and expert opinion.

Influenza is associated with a substantial health burden, especially in high-risk subjects such as older adults, frail individuals and those with underlying chronic diseases. In this review, we summarized clinical findings regarding the impact of influenza in vulnerable populations, highlighted the benefits of influenza vaccination in preventing severe illness and complications and reviewed the main evidence on the efficacy, effectiveness and safety of the vaccines that are best suited to older adults among those available in Italy. The adverse outcomes associated with influenza infection in elderly and frail subjects and those with underlying chronic diseases are well documented in the literature, as are the benefits of vaccination (mostly in older adults and in patients with cardiovascular diseases, diabetes and chronic lung disease). High-dose and adjuvanted inactivated influenza vaccines were specifically developed to provide enhanced immune responses in older adults, who generally have low responses mainly due to immunosenescence, comorbidities and frailty. These vaccines have been evaluated in clinical studies and systematic reviews by international immunization advisory boards, including the European Centre for Disease Prevention and Control. The high-dose vaccine is the only licensed influenza vaccine to have demonstrated greater efficacy versus a standard-dose vaccine in preventing laboratory-confirmed influenza in a randomized controlled trial. Despite global recommendations, the vaccination coverage in high-risk populations is still suboptimal. All healthcare professionals (including specialists) have an important role in increasing vaccination rates.

Continuous glucose monitoring (CGM) in a non-Icu hospital setting: The patient's journey.

AIMS: Although consistent data support the outpatient use of continuous glucose monitoring (CGM) to improve glycemic control and reduce hypoglycemic burden, and clinical outcomes, there are limited data regarding its use in the hospital setting, particularly in the non-intensive care unit (non-ICU) setting. The emerging use of CGM in the non-critical care setting may be useful in increasing the efficiency of hospital care and reducing the length of stay for patients with diabetes while improving glycemic control. DATA SYNTHESIS: The purpose of this Expert Opinion paper was to evaluate the state of the art and provide a practical model of how CGM can be implemented in the hospital. SETTING: A patient's CGM journey from admission to the ward to the application of the sensor, from patient education on the device during hospitalization until discharge of the patient to maintain remote control. CONCLUSIONS: This practical approach for the implementation and management of CGM in patients with diabetes admitted to non-ICUs could guide hospitals in their diabetes management initiatives using CGM, helping to identify patients most likely to benefit and suggesting how this technology can be implemented to maximize clinical benefits.

Patient perceptions of insulin therapy in diabetes self-management with insulin injection devices.

AIMS: Several insulin delivery systems are available to control glycemia in patients with diabetes. Recently introduced devices feature connectivity enabling data transfer to smartphone applications to provide decision support and reduce errors in dosing and timing, while reducing the cognitive burden. METHODS: We conducted an online survey in Italian patients with a self-reported diagnosis of diabetes to assess patient perceptions of insulin therapy management, and their impressions of connection-enabled insulin pens compared to standard insulin pens. The Morisky Medication Adherence Scale-8 was used to assess adherence to insulin therapy. RESULTS: Among 223 respondents (108 with type 1 diabetes; 115 with type 2 diabetes), the most prominent unmet need was the necessity to overcome the cognitive burden of care associated with measuring, calculating, timing, and recording therapy. Only 25% of respondents had high adherence; 28% had low adherence. CONCLUSIONS: When asked to compare the attributes of a non-connected insulin pen with those of a new connected device, 71% of patients rated the new proposal "very useful". The cognitive burden associated with self-management of diabetes therapy may influence preferences for advanced insulin delivery systems.

LDL-cholesterol control in the primary prevention of cardiovascular diseases: An expert opinion for clinicians and health professionals.

AIMS: Although adequate clinical management of patients with hypercholesterolemia without a history of known cardiovascular disease is essential for prevention, these subjects are often disregarded. Furthermore, the scientific literature on primary cardiovascular prevention is not as rich as that on secondary prevention; finally, physicians often lack adequate tools for the effective management of subjects in primary prevention and have to face some unsolved relevant issues. This document aims to discuss and review the evidence available on this topic and provide practical guidance. DATA SYNTHESIS: Available algorithms and risk charts represent the main tool for the assessment of cardiovascular risk in patients in primary prevention. The accuracy of such an estimate can be substantially improved considering the potential contribution of some additional risk factors (C-reactive protein, lipoprotein(a), family history of cardiovascular disease) and conditions (environmental pollution, sleep quality, socioeconomic status, educational level) whose impact on the cardiovascular risk has been better understood in recent years. The availability of non-invasive procedures to evaluate subclinical atherosclerosis may help to identify subjects needing an earlier intervention. Unveiling the presence of these conditions will improve cardiovascular risk estimation, granting a more appropriate intervention. CONCLUSIONS: The accurate assessment of cardiovascular risk in subjects in primary prevention with the use of algorithms and risk charts together with the evaluation of additional factors will allow physicians to approach each patient with personalized strategies, which should translate into an increased adherence to therapy and, as a consequence, a reduced cardiovascular risk.

Efficacy of Dapagliflozin in Southern Europe Across the Spectrum of Characteristics of Type 2 Diabetes: An International Real-World Analysis.

Purpose: To extend a prior real-world analysis (DARWIN-T2D) of patients with type 2 diabetes initiating dapagliflozin in Italy, Greece, and Spain by evaluating changes in glycemic and extra-glycemic endpoints after initiation of dapagliflozin. Patients and Methods: The association among demographic/clinical characteristics and the change in glycemic and extraglycemic effectiveness endpoints during the observation period was assayed using a mixed effects model. Results: A total of 1438 (860 males; 59.8%) patients were evaluated; patients were followed for a mean of 5.6 months. At baseline, 93.4% and 61.9% of patients were on concomitant metformin and insulin, respectively. A significant mean decrease in HbA1c from 8.7% to 7.5% was observed. The mixed model used also revealed several associations between different glycemic and laboratory parameters and patient characteristics at baseline; insulin use was significantly associated with lower HbA1c. Patients with BMI ≥30 kg/m2 experienced greater weight loss than those with BMI <30 kg/m2. A consistent glucose-lowering effect of dapagliflozin was seen in all subgroups of patients, including those with stage 2 renal impairment and cardiovascular disease. Conclusion: The present analysis confirms the efficacy of dapagliflozin in diversified real-world settings with broadly similar effects on HbA1c across countries and baseline characteristics.

Effectiveness and Tolerability of Once-Weekly GLP-1 Receptor Agonists in Clinical Practice: A Focus on Switching Between Once-Weekly Molecules in Type 2 Diabetes.

Aims: This study aims to evaluate the effectiveness and tolerability of once-weekly glucagon-like peptide receptor agonists (OW GLP-1RAs) and to assess the clinical benefits of switching from one GLP-1RA to another (switchers) in a routine clinical setting. Materials and Methods: This is a retrospective, real-world cohort study, based on electronic medical records utilized in one Italian diabetes clinic. Estimated mean changes in HbA1c and body weight after 6 and 12 months from the first prescription of a long-acting GLP1-RA were evaluated using longitudinal linear mixed models for repeated measures. The effectiveness of the three long-acting GLP1-RAs was compared separately in the GLP1-RA naive and switchers cohorts, after propensity score adjustment. Results: Initiating a long-acting GLP1-RA was associated with statistically significant improvements in HbA1c (-1%) and body weight (-2.6 kg) after 6 months, and benefits were maintained after 12 months. In GLP1-RA naive cohort, semaglutide showed the largest effect on HbA1c (-1.55%; 95%CI, -1.77;-1.34) and body weight (-3.76 kg; 95%CI, -5.05;-2.47) at 6 months, maintained at 12 months (-1.55%; 95%CI, -1.82;-1.28 and -6.29 kg; 95%CI, -7.94;-4.63). In the switchers' cohort, statistically significant reductions at 6 months in HbA1c and body weight were documented with semaglutide and dulaglutide only, with semaglutide associated with the most marked reduction (-0.84%; 95%CI, -1.03;-0.65 and -3.43 kg; 95%, -4.67;-2.19). Dropout rates were 9.2%, 28.5%, and 41.7% in semaglutide, dulaglutide, and exenatide groups, respectively. Conclusions: The effectiveness and tolerability of the OW GLP-1RAs in the real world were documented. Semaglutide was associated with the highest response without impact on safety. Clinical improvements were obtained even in switchers, especially in those switching to semaglutide.

Health care organization and use of technological devices in people with diabetes in Italy: Results from a survey of the Working Group on Diabetes and Technology.

BACKGROUND AND AIM: The use of technology offers recognized benefits to persons with diabetes. The aim of this study was to evaluate the organization of healthcare facilities, the composition of the diabetes team, and the use of Continuous Subcutaneous Insulin Infusion (CSII) and Continuous Glucose Monitoring (CGM) in Italy. METHODS AND RESULTS: Diabetes care centers were asked to complete a web survey based on information collected in 2018. Sixty-one pediatric and 243 adult centers participated in the survey, accounting for 507,386 patients, mostly with type 2 diabetes (86.4%). Fifty-three percent of pediatric centers and 11% of adult centers reported a team composed of diabetologists, nurses, and psychologists. Overall, 13,204 patients (2.6%) were using CSII (95% with type 1 diabetes), and 28,936 (5.7%), were using CGM (74% with type 1 diabetes). When stratifying for the type of diabetes, 24% and 40.8% of patients with type 1 were using CSII and CGM, respectively, whereas low use of technology was reported for patients with type 2 and women with gestational diabetes. The percentage of adult and pediatric patients with type 1 diabetes on CSII and CGM was respectively 21% and 32%, and 35% and 57%. CONCLUSIONS: The spread of CGM and CSII increased in Italy between 2013 and 2018. However, the percentage of users is still lower than what is expected based on clinical indications for use of technology. The inadequate number of professionals in the diabetes care team and insufficient economic resources are relevant barriers to disseminating technology for diabetes management.

IDegLira for the Real-World Treatment of Type 2 Diabetes in Italy: Protocol and Interim Results from the REX Observational Study.

INTRODUCTION: IDegLira was shown to maintain glycemic control while reducing risk of hypoglycemia and body weight gain. The REX study was designed to generate real-world evidence on the use of IDegLira in Italian clinical practice in two different subgroups of patients, those switching to IDegLira from a basal insulin-supported oral therapy (BOT group) and those from a basal plus bolus insulin regimen (BB group). METHODS: Adult patients with T2D diagnosed for at least 12 months and having started IDegLira 2-3 months prior to enrolment, coming from a BOT or BB regimen, were enrolled in this multicenter observational prospective cohort study conducted in 28 Italian centers. This paper presents the methodological framework of the REX study and provides the interim analysis results describing the patients' baseline characteristics and the clinical reasons for IDegLira treatment initiation. RESULTS: Of the 360 patients enrolled in the REX study, 331 were considered eligible for this interim analysis, 76.4% in the BOT and 23.6% in the BB group. Mean (SD) HbA1c was 8.5% (1.4) in the BOT and 8.2% (1.7) in the BB group. The most common T2D complications were diabetic macroangiopathy and diabetic nephropathy in both groups. The median (interquartile range) insulin daily dose before IDegLira was 15.0 (10.0-20.0) units in the BOT group and 42 (30.0-52.0) in the BB group. Oral antidiabetics were taken by 98% and 51.3% of patients, respectively. The main reason for switching to IDegLira was the inadequate glycemic control in the BOT group (86% of patients), and the intent to simplify the treatment in the BB group (66.7%). CONCLUSIONS: IdegLira is initiated after BOT in inadequately controlled patients to improve glycemic control, whereas in BB patients it is used to simplify the therapeutic regimen. Final results of the REX study will shed light on patients' outcomes after IdegLira treatment under routine clinical care.

Semaglutide reduces cardiovascular events regardless of metformin use: a post hoc subgroup analysis of SUSTAIN 6 and PIONEER 6.

BACKGROUND: Cardiovascular outcome trials (CVOTs) are conducted on a background of standard of care including metformin. These analyses sought to determine whether the cardiovascular (CV) effects of semaglutide and other glucagon-like peptide-1 receptor agonists (GLP-1RAs) vary according to baseline metformin use. METHODS: A post hoc analysis was conducted using pooled SUSTAIN 6 and PIONEER 6 CVOT data in subjects with and without metformin use at baseline. Additionally, a trial-level meta-analysis was conducted using data from seven CVOTs with GLP-1RAs-SUSTAIN 6, PIONEER 6, HARMONY OUTCOMES, LEADER, REWIND, EXSCEL and AMPLITUDE-O-including adults with type 2 diabetes at high CV risk, and a primary endpoint of time to first major adverse CV event (MACE). RESULTS: In the post hoc analysis, the no-metformin subgroup was older, with a higher body mass index, lower estimated glomerular filtration rate and higher CV risk at baseline vs the metformin subgroup. Hazard ratios (95% confidence intervals) for the reduction in risk of MACE with semaglutide vs placebo in the metformin and no-metformin subgroups were 0.70 (0.55;0.89) and 0.86 (0.60;1.22), respectively. No significant interaction between the treatment effect on MACE and metformin subgroup was observed. Findings for other CV endpoints were similar. In the meta-analysis, treatment effect (GLP-1RA vs placebo) on CV outcomes was no different with vs without baseline metformin (overall ratio between the hazard ratios for metformin vs no-metformin 1.09 [0.96;1.22]). CONCLUSION: These findings indicate that the CV outcomes for semaglutide were similar regardless of baseline metformin use, which may also apply to all GLP-1RAs. Trial registration SUSTAIN 6 (NCT01720446), PIONEER 6 (NCT02692716).

A guide for the use of LibreView digital diabetes platform in clinical practice: Expert paper of the Italian Working Group on Diabetes and Technology.

Wider access to continuous glucose monitoring systems, including flash glucose monitoring, has enabled people with diabetes to achieve lower HbA1c levels and reduce the amount of time they spend in hypoglycaemia or hyperglycaemia, and has improved their quality of life. An International Consensus Panel proposed different target glucose ranges and recommendations according to different ages and situations (adults, young people and children with type 1 or type 2 diabetes, as well as elderly people who are at higher risk of hypoglycaemia, and women with diabetes during pregnancy). In this expert opinion, we interpret the international recommendations in the context of established clinical practice for diabetes care, and propose three different step-by-step algorithms to help the healthcare professionals use the most innovative glucose metrics, including time in glucose ranges, glucose management indicator, coefficient of variation, and ambulatory glucose profile. In detail, we focus on glucose metrics as measured by the FreeStyle Libre system and as visualized on the LibreView digital diabetes platform to support appropriate interpretation of flash glucose monitoring data. This is specifically structured for healthcare professionals and general practitioners who may have a low level of confidence with diabetes technology, with the aim of optimizing diabetes management, ensuring effective use of healthcare resources and to maximise outcomes for people with diabetes.

[Unmet clinical need and new therapeutic options.] / Unmet clinical need e nuovi farmaci.

The debate around unmet clinical need (UCN) is still very much alive. How do we define UCN? How does it influence the definition of clinically relevant outcomes in a therapeutic area? Who defines UCN? What are the consequences of recognizing different grading of UCN? In this paper we will address these questions and finally formulate proposals for the Italian context. The paper is based on a discussion within a panel of experts. This topic is even more stimulating as this work takes place in a historical period which, on the one hand, sees the start of a new course of negotiation rules recently published by AIFA and, on the other hand, poses unprecedented challenges that emerged during the pandemic crisis. The working group formulated suggestions and proposals to further enhance the role of the UCN in decision-making processes, also in the light of the new negotiation procedure, and to help refine the tools for grading the UCN and the value of medicines in the interests of patients and society as a whole.

Effects of liraglutide vs. lifestyle changes on soluble suppression of tumorigenesis-2 (sST2) and galectin-3 in obese subjects with prediabetes or type 2 diabetes after comparable weight loss.

BACKGROUND: Soluble suppression of tumorigenesis-2 (sST2) and galectin (Gal)-3 are two biomarkers related to inflammation, metabolic disturbances and to myocardial fibrosis that characterize several cardiac pathological conditions. Increased circulating levels of these molecules have been associated with risk of cardiovascular death. Treatment with liraglutide, a glucagon-like peptide 1 analog, is associated with weight loss, improved glycemic control, and reduced cardiovascular risk. We wanted to assess (I) potential differences between subjects with prediabetes or type 2 diabetes mellitus (T2DM) and healthy controls in sST2 and Gal-3 circulating levels, and their relationship with glycemic control and markers of beta cell function and myocardial injury; (II) whether liraglutide treatment modulates these markers in subjects with prediabetes or early T2DM independently of weight loss; (III) whether baseline levels of any of these two molecules may predict the response to liraglutide treatment. METHODS: Forty metformin-treated obese subjects (BMI ≥ 30) with prediabetes [impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) or both (n = 23)] or newly diagnosed T2DM (n = 17), were randomized to liraglutide or lifestyle counseling until achieving a comparable weight loss (7% of initial body weight). Thirteen subjects were enrolled as healthy controls for baseline sST2 and Gal-3 levels. RESULTS: Baseline sST2 levels were comparable between controls and obese patients (p = 0.79) whereas Gal-3 levels were significantly higher in patients as compared to controls (p < 0.001). Liraglutide treatment, but not weight loss achieved by lifestyle counseling, decreased plasma sST2 levels (- 9%, beta = - 14.9, standard deviation 6.9, p = 0.037) while Gal-3 levels did not change. A reduction in serum hs-Troponin I was observed after intervention, due to a 19% (p = 0.29) increase in the lifestyle arm, and a 25% decrease (p = 0.033) in the liraglutide arm (between-group difference p = 0.083). Lower baseline Gal-3 levels predicted a better improvement in beta cell function after liraglutide treatment. CONCLUSIONS: Liraglutide-induced reduction in sST2 and possibly hs-TnI suggests that in obese patients with prediabetes or early T2DM this drug may have a positive effect on (cardiac) fibrosis, whereas plasma level of Gal-3 before liraglutide initiation may predict response to the drug in terms of beta cell function improvement. Trial registration Eudract: 2013-001356-36.