Aims: To evaluate costs in patients with diabetes who experienced a macrovascular complication from a Brazilian public healthcare system perspective. Materials and methods: A retrospective, observational study that utilized the database of the Brazilian Unified Health System (DATASUS). Data for direct medical costs (hospitalization and outpatient) were extracted for patients with diabetes and a macrovascular complication (1 January 2012-31 December 2018) and converted to US Dollars (2019 USD). Mixed-effects logistic regression explored associations between demographic and clinical characteristics with the incurrence of high direct medical costs. Results: In total, 1,668 (0.2%) patients with diabetes met study inclusion criteria and experienced a macrovascular complication, either alone (N ¼ 1,193) or together with a microvascular complication (N ¼ 475). Median [95% CI] annual costs (USD/patient) were 130.5 [90.7; 264.2] at baseline, increasing to 334.0 [182.2; 923.5] in the first year after the complication. The odds of incurring high costs were significantly elevated in the first and second year (vs. baseline), and in patients who experienced a macrovascular and microvascular complication (vs. macrovascular alone) (all p < 0.001). Limitations: The DATASUS database does not cover primary care (it covers secondary and tertiary care), adding a selection bias to the sample. Additionally, our findings may not be representative of the entire Brazilian population given that approximately 75% of the population of Brazil depend exclusively on the SUS, while the remaining 25% have some access to private healthcare. Conclusions: This study has demonstrated higher medical costs from the perspective of the Brazilian public healthcare system in patients with diabetes after experiencing a macrovascular complication, either alone or in conjunction with a microvascular complication, in comparison with costs before the complication(s). In addition to providing up-to-date cost estimates, our findings highlight the need to implement strategies to reduce the cardiovascular risk in Brazilian patients with diabetes and drive cost savings.

The randomized, double-blind, cardiovascular outcomes trials LEADER (NCT01179048) and SUSTAIN 6 (NCT01720446) showed cardiovascular risk reduction in patients with type 2 diabetes treated with liraglutide and semaglutide, respectively, compared with placebo. This post hoc analysis examined the impact of microvascular disease at baseline on cardiovascular outcomes in these trials, and the efficacy of liraglutide (1.8 mg) and once-weekly semaglutide (0.5-1.0 mg) in patients with and without microvascular disease. In total, 9340 patients from LEADER and 3297 patients from SUSTAIN 6 were included in this analysis; of these, 5761 and 2356 had a history of microvascular disease at baseline and 3835 and 1640 had a history of both microvascular and macrovascular disease, respectively. Patients with microvascular disease were shown to have an increased risk of major adverse cardiovascular events compared with patients without microvascular disease (hazard ratio

BackgroundPreclinical, clinical, and real‐world evidence suggest benefits in Alzheimer’s disease (AD)‐related symptoms and reduced risk of dementia in type 2 diabetes following treatment with glucagon‐like peptide 1 receptor agonists (GLP‐1RA; Figure 1). The phase 3 evoke and evoke+ trials (NCT04777396 and NCT04777409, respectively) will assess the efficacy and safety of the oral GLP‐1RA semaglutide versus placebo in participants with early AD. Here, we present the design of these trials.Methodevoke and evoke+ are two randomized, double‐blind, placebo‐controlled trials (Figure 2) recruiting across 38 countries, with 2 further countries pending (Figure 3). In each trial, a planned 1,840 amyloid‐positive participants (aged 55 to 85 years) with mild cognitive impairment (MCI) due to AD (Clinical Dementia Rating [CDR] global = 0.5) or mild AD dementia (CDR global = 1.0) will be randomized (1:1) to oral semaglutide 14 mg once‐daily (escalated via 3‐ and 7‐mg doses over 8 weeks) or placebo for 156 weeks. Participants may use approved AD treatments if on a stable dose ≥3 months before screening. Other key inclusion criteria are: Mini‐Mental State Examination score ≥22 and Repeatable Battery for the Assessment of Neuropsychological Status delayed memory index score ≤85. The key difference between the trials is the inclusion of ≥20% of participants with significant small vessel co‐pathology in evoke+. The primary endpoint is change in the CDR – Sum of Boxes score from baseline to week 104. Confirmatory secondary endpoints are change in Alzheimer’s Disease Cooperative Study‐Activities of Daily Living‐MCI score, and time to progression to dementia among participants with MCI at baseline. Exploratory endpoints include effects on neurodegeneration and neuroinflammation assessed by changes in plasma and cerebrospinal fluid biomarkers. After week 104, participants will continue their original randomized, double‐blind, placebo‐controlled treatment for a 52‐week extension phase followed by a 5‐week follow‐up, allowing assessment of the long‐term effects of semaglutide. A full list of endpoints is provided in Figure 4.ResultThe evoke and evoke+ read‐outs are expected in 2025.Conclusionevoke and evoke+ will be the first large‐scale phase 3 trials (Ntotal = 3,680) to investigate the hypothesized neuroprotective disease‐modifying effect of semaglutide in early AD.

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Aim To assess the potential gain in the number of life‐years free of a (recurrent) cardiovascular disease (CVD) event with optimal cardiovascular risk management (CVRM) and initiation of glucose‐lowering agents with proven cardiovascular benefit in people with type 2 diabetes (T2D). Materials and Methods 9,416 individuals with T2D from the CAPTURE study, a non‐interventional, cross‐sectional, multinational study, were included. The diabetes lifetime‐perspective prediction model was used for calculating individual 10‐year and lifetime CVD risk. The distribution of preventive medication use was assessed according to predicted CVD risk and stratified for history of CVD. For the estimation of absolute individual benefit from lifelong preventive treatment, including optimal CVRM and the addition of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2is), the model was combined with treatment effects from current evidence. Results GLP‐1 RA or SGLT‐2i use did not greatly differ between patients with and without CVD history, while use of blood pressure‐lowering medication, statins and aspirin was more frequent in patients with CVD. Mean (standard deviation [SD]) lifetime benefit from optimal CVRM was 3.9 (3.0) and 1.3 (1.9) years in patients with and without established CVD, respectively. Further addition of a GLP‐1 RA and an SGLT‐2i in patients with CVD gave an added mean (SD) lifetime benefit of 1.2 (0.6) years. Conclusions Life‐years gained free of (recurrent) CVD by optimal CVRM and the addition of a GLP‐1 RA or aSGLT‐2i is dependent on baseline CVD status. These results aid individualizing prevention and promote shared decision‐making in patients with T2D.