Freddy Goldberg Eliaschewitz

Introdução: Apesar dos avanços no manejo da doença renal crônica (DRC), o diagnóstico precoce e a estratificação de risco permanecem grandes desafios. Este estudo analisou dados nacionais derivados de uma campanha brasileira de rastreamento da DRC, voltada para indivíduos de alto risco que desconheciam sua condição, visando estimar a prevalência da doença e avaliar tendências longitudinais na taxa de filtração glomerular estimada (TFGe).

Introduction: Despite advances in chronic kidney disease (CKD) management, early diagnosis and risk stratification remain major challenges. This study analyzed national data derived from a Brazilian CKD screening campaign, targeting high-risk individuals unaware of their condition, to estimate CKD prevalence and evaluate longitudinal trends in estimated glomerular filtration rate (eGFR). Methods: This cross-sectional, observational study evaluated adults with diabetes mellitus (DM) and/or arterial hypertension, previously undiagnosed with CKD, who participated in a CKD screening campaign. Demographic, clinical, and laboratory data—including serum creatinine and albumin-to-creatinine ratio (ACR)—were collected. CKD staging followed Kidney Disease: Improving Global Outcomes (KDIGO) criteria, and eGFR was calculated using the CKD-EPI 2021 equation. Mixed effect models were used to assess eGFR trajectories and logistic regression was used to examine CKD risk factors. Results: Among 14,239 high-risk participants (mean age 54 years; 84% hypertensive; 37% diabetic), CKD was newly identified in 19.6%, with 11.3% showing eGFR 30 mg/g. Despite abnormal ACR results, testing remained uncommon: 25 kg/m2 (+60%). Logistic regression models of risk projected ~169,000 kidney failure cases in 2 years and ~500,000 in 5 years, excluding competing mortality risk. Conclusion: A high prevalence of previously undiagnosed CKD was found in this high-risk population. Despite universal access to testing in Brazil, albuminuria remains markedly underused, representing a missed opportunity for early detection and implementation of nephroprotective interventions.

Purpose of Review To discuss evidence supporting the use of glucagon-like peptide 1 receptor agonists (GLP-1RA) to treat obesity and their role as a cardioprotective drug. Obesity is not just a hypertrophy of the adipose tissue because it may become dysfunctional and inflamed resulting in increased insulin resistance. Being overweight is associated with increased incidence of cardiovascular events and weight loss achieved through lifestyle changes lowers risk factors, but has no clear effect on cardiovascular outcomes. In contrast, treating obesity with GLP-1RA decreases cardiovascular risk and the possible mechanisms of cardioprotection achieved by this class of drugs are discussed. GLP-1RA were initially developed to treat type 2 diabetes patients, in whom the effects upon glycemia and, moreover, weight loss, especially with long-acting GLP-1RA, were evident. However, cardiovascular safety trials in type 2 diabetes patients, the majority presenting cardiovascular disease and excess weight, showed that GLP-1 receptor agonists were indeed capable of decreasing cardiovascular risk. Recent Findings Type 2 diabetes treatment with GLP-1RA liraglutide and semaglutide paved way to a ground-breaking therapy specific for obesity, as shown with the SCALE 3 mg/day liraglutide program and the STEP 2.4 mg/week semaglutide program. A novel molecule with superior performance is tirzepatide, a GLP-1 and GIP (Gastric Inhibitory Peptide) receptor agonist and recent results from the SURPASS and SURMOUNT programs are briefly described. Liraglutide was approved without a CVOT (Cardiovascular Outcome Trial) because authorities accepted the results from the LEADER study, designed for superiority. The SELECT study with semaglutide will report results only in 2023 and tirzepatide is being tested in patients with diabetes in the SURPASS-CVOT. Summary Clinical studies highlight that GLP-1RA to treat obesity, alongside their concomitant cardioprotective effects, have become a hallmark in clinical science.

Background: There is currently a large arsenal of antidiabetic drugs available to treat type 2 diabetes (T2D). However, this is a serious chronic disease that affects millions of adults worldwide and is responsible for severe complications, comorbidities, and low quality of life when uncontrolled due mainly to delays in initiating treatment or inadequate therapy. This review article aims to clarify the therapeutic role of the oral formulation of the glucagon-like peptide 1 receptor agonist (GLP-1 RA) semaglutide in treating typical T2D patients. The discussion focused on metabolic, glycemic, and weight alteration effects and the safety of the therapy with this drug. Main text: Therapy with glucagon-like peptide 1 receptor agonist (GLP-1 RA) promotes strategic changes in the pathophysiological pathway of T2D and improves the secretion of glucagon and insulin, which results in a reduction in blood glucose levels and the promotion of weight loss. Until recently, the only route for semaglutide administration was parenteral. However, an oral formulation of GLP-1 RA was recently developed and approved by the Brazilian Health Regulatory Agency (ANVISA) and the Food and Drug Administration (FDA) based on the Peptide Innovation for Early Diabetes Treatment (PIONEER) program results. A sequence of 10 clinical studies compared oral semaglutide with placebo or active standard-of-care medications (empagliflozin 25 mg, sitagliptin 100 mg, or liraglutide 1.8 mg) in different T2D populations. Conclusions: Oral semaglutide effectively reduces glycated hemoglobin (HbA1c) levels and body weight in a broad spectrum of patients with T2D and shows cardiovascular safety. Oral semaglutide broadens therapy options and facilitates the adoption of earlier GLP-1 RA treatment once T2D patients present low rates of treatment discontinuation. The main adverse events reported were related to the gastrointestinal tract, common to GLP-1 RA class drugs.

Type 2 diabetes mellitus (T2DM) is a major independent risk factor for cardiovascular disease, and diabetic dyslipidemia is a major contributor to cardiovascular risk in these patients. Here we report the rationale and design of a phase 3, double‐blind study specifically designed to evaluate the lipid‐lowering efficacy of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab in patients with T2DM and hyperlipidemia or mixed dyslipidemia who are on background statin therapy. In the BERSON (evolocumaB Efficacy for LDL‐C Reduction in subjectS with T2DM On background statiN) trial, patients with T2DM, a screening low‐density lipoprotein cholesterol (LDL‐C) level of ≥ 2.6 mmol/L (≥100 mg/dL) or ≥ 3.4 mmol/L (≥130 mg/dL), and with or without statin treatment at screening, respectively, were enrolled and started on atorvastatin 20 mg/day for a lipid stabilization period of at least 4 weeks. Then, patients were randomly assigned in a 2:2:1:1 ratio to receive atorvastatin 20 mg once daily plus either evolocumab 140 mg every 2 weeks (Q2W), evolocumab 420 mg every month (QM), placebo Q2W, or placebo QM. The co‐primary outcome measures were the percentage change from baseline in LDL‐C at week 12 and the percentage change from baseline in LDL‐C at the mean of weeks 10 and 12. The BERSON trial has completed enrollment. The study completed in the first half of 2018, and will provide information on the efficacy and safety of evolocumab in patients with T2DM and dyslipidemia.

Diabetes mellitus (DM) is a public health issue, affecting around 382 million people worldwide. In order to achieve glycemic goals, insulin therapy is the frontline therapy for type 1 DM patients; for patients with type 2 DM, use of insulin therapy is an option as initial or add-on therapy for those not achieving glycemic control. Despite insulin therapy developments seen in the last decades, several barriers remain for insulin initiation and optimal maintenance in clinical practice. Fear of hypoglycemia, weight gain, pain associated with blood testing and injection-related pain are the most cited reasons for not starting insulin therapy. However, new generation of basal insulin formulations, with longer length of action, have shown the capability of providing adequate glycemic control with lower risk of hypoglycemia.

The development of extended-action insulin analogues was motivated by the unfavorable pharmacokinetic (PK) profile of the conventional long-acting insulin formulations, generally associated with marked inter and intra patient variability and site- and dose-dependent effect variation. The new ultra-long insulin analogue degludec (IDeg) has the same amino acid sequence as human insulin except for the removal of threonine in the position 30 of the B chain (Des-B30, “De”) and the attachment, via a glutamic acid linker (“glu”), of a 16-carbon fatty diacid (hexadecanoic diacid, “dec”) to lysine in the position 29 of the B chain. These modifications allow that, after changing from the pharmaceutical formulation to the subcutaneous environment, IDeg precipitates in the subcutaneous tissue, forming a depot that undergoes a highly predictable gradual dissociation. Thus, once-daily dosing of IDeg results in a low peak: trough ratio, with consequent low intra-individual variability and plasmatic concentrations less critically dependent upon the time of injections. The clinical development program of IDeg (BEGIN) was comprised of 9 therapeutic confirmatory trials of longer duration (26–52 weeks) and showed that the efficacy of IDeg is comparable to insulin glargine in type 1 (T1D) and type 2 (T2D) diabetes patients across different age, body mass index and ethnic groups. This new ultra-long insulin analogue presents as advantages flexibility in dose timing and lower risk of hypoglycemia.

Type 2 diabetes mellitus (T2DM) is one of the most important epidemic diseases in the world this century, and accounts for 90% of cases of diabetes globally. Brazil is one of the most important examples of the alarming picture of T2DM in emergent societies, being the country with the fourth largest number of people with diabetes. The aim of this paper is to review the literature on diabetes in Brazil, specifically looking at the epidemiology and management of T2DM. A literature search was conducted using PubMed and LILACS to identify articles containing information on diabetes in Brazil. Official documents from the Brazilian government, World Health Organization, and International Diabetes Federation were also reviewed.