PRE1BRAZIL Protocol: A Randomized Controlled Trial to Evaluate the Effectiveness and Safety of the DPP-4 Inhibitor Alogliptin in Delaying the Progression of Stage 2 Type 1 Diabetes

Jaquellyne Gurgel Penaforte-Saboia,1,2,* Carlos Eduardo Barra Couri,3,* Natasha Vasconcelos Albuquerque,2,4,* Lana Livia Peixoto Linard,1,2,* Daniel Autran Cavalcante Araújo,5,* Sherida Karanini Paz de Oliveira,6 Thisciane Ferreira Pinto Gomes,2 Marcelo Maia Pinheiro,7 Maria Helane Costa Gurgel Castelo,2 Virgínia Oliveira Fernandes,2,4 Renan Magalhães Montenegro Júnior1,2,4,* 1Department of Clinical Medicine, Federal University of Ceará, Fortaleza, CE, Brazil; 2Clinical Research Unit, Walter Cantídio University Hospital, Federal University of Ceará/ EBSERH Fortaleza, Fortaleza, CE, Brazil; 3Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil; 4Department of Community Health, Federal University of Ceará, Fortaleza, CE, Brazil; 5Department of Internal Medicine, Sinai Grace Hospital/Detroit Medical Center, Detroit, MI, USA; 6Ceará State University, Fortaleza, CE, Brazil; 7UNIVAG, University Center, Faculty of Medicine, Várzea Grande, Mato Grosso, Brazil*These authors contributed equally to this workCorrespondence: Renan Magalhães Montenegro Júnior, Hospital Complex (CH) of UFC/EBSERH, Rua Coronel Nunes de Melo 1142, Fortaleza, Ceará, 60430-270, Brazil, Tel +55 8533668600, Fax +55 8533668619, Email [email protected]: The incidence of Type 1 Diabetes Mellitus (T1DM) is on the rise. Since there is no curative treatment, it is urgent to look for therapies that can delay disease progression and protect pancreatic β-cells. Dipeptidyl peptidase-4 inhibitors (DPP-4i) have shown potential in modulating inflammation and preventing β-cell destruction. This protocol describes an upcoming trial to evaluate the effectiveness of the DPP-4i alogliptin in delaying the progression of stage 2 (presymptomatic) to stage 3 (symptomatic) T1DM.Patients and Methods: We propose a two-year, two-arm, multicenter, randomized, open-label clinical trial targeting Brazilian patients aged 18 to 35 with stage 2 T1DM. The study, facilitated by the custom-developed “PRE1BRAZIL” web application, aims to enroll 130 participants. They will be randomly assigned in a 1:1 ratio to either a treatment group (alogliptin 25 mg daily plus regular clinical and laboratory assessments) or a control group (regular assessments only). The primary outcome is the rate of progression to stage 3 T1DM. Secondary outcomes include changes in A1c levels, glucose levels during a 2-hour oral glucose tolerance test (OGTT), C-peptide levels, exogenous insulin requirements, Insulin-Dose Adjusted A1c (IDAA1c), and the incidence of diabetic ketoacidosis (DKA) in those advancing to stage 3.Discussion: This protocol outlines the first randomized clinical trial (RCT) to investigate the impact of a DPP-4i in the presymptomatic stage of T1DM. The trial is designed to provide critical insights into the role of DPP-4i in the secondary prevention of T1DM. Utilizing the “PRE1BRAZIL” web application is expected to enhance participant enrollment and reduce operational costs.Registration: Brazilian Registry of Clinical Trials.Keywords: type 1 diabetes, web applications, DPP-4i, stage 2 T1DM, clinical trial protoco

Portuguese-Brazilian evidence-based guideline on the management of hyperglycemia in type 2 diabetes mellitus

Background: In current management of type 2 diabetes (T2DM), cardiovascular and renal prevention have become important targets to be achieved. In this context, a joint panel of four endocrinology societies from Brazil and Portugal was established to develop an evidence-based guideline for treatment of hyperglycemia in T2DM. Methods: MEDLINE (via PubMed) was searched for randomized clinical trials, meta-analyses, and observational studies related to diabetes treatment. When there was insufficient high-quality evidence, expert opinion was sought. Updated positions on treatment of T2DM patients with heart failure (HF), atherosclerotic CV disease (ASCVD), chronic kidney disease (CKD), and patients with no vascular complications were developed. The degree of recommendation and the level of evidence were determined using predefined criteria. Results and conclusions: In non-pregnant adults, the recommended HbA1c target is below 7%. Higher levels are recommended in frail older adults and patients at higher risk of hypoglycemia. Lifestyle modification is recommended at all phases of treatment. Metformin is the first choice when HbA1c is 6.5-7.5%. When HbA1c is 7.5-9.0%, dual therapy with metformin plus an SGLT2i and/or GLP-1RA (first-line antidiabetic agents, AD1) is recommended due to cardiovascular and renal benefits. If an AD1 is unaffordable, other antidiabetic drugs (AD) may be used. Triple or quadruple therapy should be considered when HbA1c remains above target. In patients with clinical or subclinical atherosclerosis, the combination of one AD1 plus metformin is the recommended first-line therapy to reduce cardiovascular events and improve blood glucose control. In stable heart failure with low ejection fraction ( 30 mL/min/1.73 m2, metformin plus an SGLT-2i is recommended to reduce cardiovascular mortality and heart failure hospitalizations and improve blood glucose control. In patients with diabetes-associated chronic kidney disease (CKD) (eGFR 30-60 mL/min/1.73 m2 or eGFR 30-90 mL/min/1.73 m2 with albuminuria > 30 mg/g), the combination of metformin and an SGLT2i is recommended to attenuate loss of renal function, reduce albuminuria and improve blood glucose control. In patients with severe renal failure, insulin-based therapy is recommended to improve blood glucose control. Alternatively, GLP-1RA, DPP4i, gliclazide MR and pioglitazone may be considered to reduce albuminuria. In conclusion, the current evidence supports individualizing anti-hyperglycemic treatment for T2DM.This article publication was funded by Sociedade Brasileira de Diabetes (SBD)