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