Eficácia dos inibidores da DPP-4 em pacientes com diabetes autoimune: uma revisão sistemática e metanálise

Abstract

Introduction: Type 1 diabetes mellitus (T1DM) and latent autoimmune diabetes of adults (LADA) are autoimmune diseases characterized by insulin deficiency due to beta-cell destruction. Adjunctive therapies to insulin, such as dipeptidyl peptidase 4 inhibitors (DPP-4i), have been explored to improve glycemic control and reduce insulin requirements, but their efficacy remains controversial. Recent evidence suggests additional benefits regarding immunomodulation, beta-cell preservation and synergistic effect with advanced diabetes treatment technologies. Objectives: To evaluate the efficacy and safety of DPP-4i as an adjunctive therapy in T1DM and LADA, updating the evidence base with new studies. Method: This systematic review and meta-analysis was conducted in accordance with Cochrane methodology and reported following the PRISMA guidelines. Searches were conducted in PubMed, Capes Journals, Embase, LILACS/VHL, Epistemonikos, and Cochrane Library databases up to June 30, 2025, with no restrictions on date or language. Data from eligible studies were extracted using a standardized form, and methodological quality and certainty of evidence were assessed using the RoB 2 tool and the GRADE framework, respectively. Data synthesis was performed qualitatively using a narrative approach and quantitatively through meta-analyses. The protocol was prospectively registered in the PROSPERO database under the identifier CRD42024507616. Results: Twenty-eight randomized controlled trials (1477 participants) were included. DPP-4i had a significant effect on reducing HbA1c (p = 0.0006) and increasing fasting C-peptide (p = 0.0012). They also produced significant reductions in fasting plasma glucose, postprandial glucose and daily insulin dose, alongside an increase in time in range and a reduction in time above range. No significant impact was observed on BMI, time below range or hypoglycemic episodes. Conclusions: DPP-4is improve glycemic control, reduce insulin requirements and show evidence of partial preservation of beta-cell function. The benefits were more consistent in patients with LADA with recent diagnosis, and in those with greater residual beta-cell reserve, suggesting that early intervention is crucial for efficacy. Further trials focusing on more favorable phenotypes and standardized immunological outcomes are required to consolidate these findings.