ORAL GLP-1 RECEPTOR AGONIST (ORFORGLIPRON) IN THE MANAGEMENT OF OBESITY AND TYPE 2 DIABETES

Abstract

Orforglipron (LY3502970) is the first small-molecule, non-peptidic oral agonist of the glucagon-like peptide-1 (GLP-1) receptor, developed for the treatment of obesity and type 2 diabetes mellitus (T2DM). This study conducted a narrative literature review, of a descriptive and qualitative nature, aiming to compile and critically analyze scientific evidence published between 2015 and 2025 regarding the pharmacology, clinical efficacy, safety, and therapeutic applicability of this agent. The literature search was performed in PubMed, SciELO, ScienceDirect, and ClinicalTrials.gov, using controlled descriptors from the DeCS and MeSH vocabularies. A total of 19 studies, including randomized clinical trials, systematic reviews, and meta-analyses, were included. Findings demonstrated mean reductions in glycated hemoglobin (HbA1c) of 1.3–1.6% and body weight loss of 10–15%, with a favorable safety profile and mild to moderate gastrointestinal effects. Additionally, improvements were observed in cardiometabolic parameters, such as blood pressure, LDL cholesterol, and high-sensitivity C-reactive protein, suggesting a possible indirect cardioprotective effect. In conclusion, Orforglipron represents a significant innovation in metabolic therapy, combining clinical efficacy, dosing convenience, and potential cardiovascular benefit. However, its clinical consolidation will depend on the completion of ongoing phase 3 multicenter trials, which are expected to confirm its effects on long-term clinical outcomes.

DOI: https://doi.org/10.56238/sevened2026.009-004