Dipeptidyl Peptidase-4 (DPP-4) Inhibitor Therapy in the Management of Latent Autoimmune Diabetes in Adults (LADA): A Systematic Review and Meta Analysis

Abstract

Objective: Latent autoimmune diabetes in adults (LADA) has been shown in recent studies to have heterogeneous pathophysiology and phenotype. Although insulin is considered as the therapeutic choice for these patients, other antidiabetic drugs have been studied in terms of glycemic control and beta cell function preservation. In particular, dipeptidyl peptidase-4 (DPP-4) inhibitors have shown immunomodulatory effects in animal models since it was demonstrated a higher DPP-4 activity in patients with LADA compared to patients with Type 1 and Type 2 diabetes suggesting a possible effect on autoimmunity found in LADA. This study aims to review the outcomes of the included studies and evaluate the efficacy of DPP-4 inhibitors in the treatment of LADA. Methods: We searched Medline, Embase, PubMed and Cochrane Library Databases and ClinicalTrials.gov for studies concerning the use of DPP4 inhibitors in patients with latent autoimmune diabetes in adults (LADA). Results: Preclinical studies demonstrated drug’s immunomodulatory effects in terms of suppression of inflammatory processes and oxidative stress providing endothelial protection leading to improved metabolic control and prevention of vasculopathy. From this meta-analysis, pooled data from 8 randomized controlled trials revealed that the use of DPP-4 inhibitors in LADA patients resulted in an improved glycemic control, decreased insulin requirement and increased beta cell function as assessed by a decrease in GADA titers, increased C peptide levels and HOMA B. Conclusion: Beneficial effects of DPP4 inhibitors are shown by the included studies indicating that they are promising therapeutic agents for patients with LADA. However, caution should still be exercised since there is still much to learn about the disease itself and larger scale prospective randomized trials are needed to assess the efficacy and safety of DPP4 inhibitors for these patients.