Moreira, Helena SilvaMoreira, FernandoJesus, ÂngeloSoares, Matilde MonteiroSantos, PauloMoreira, Fernando2025-11-062025-11-062025-10-09Silva-Moreira, H., Moreira, F., Jesus, Â., Monteiro-Soares, M., & Santos, P. (2025). Factors Influencing the Prescription of First-Line Treatment for Type 2 Diabetes Mellitus: A Systematic Review. Diabetology, 6(10), 114. https://doi.org/10.3390/diabetology6100114http://hdl.handle.net/10400.22/30755Understanding prescribing patterns for type 2 diabetes mellitus, a complex condition affecting over 10% of the global adult population, can optimise prescribing practices, guide policymakers in promoting evidence-based medicine, and help tailor first-line treatments to individual characteristics or specific subgroups, improving patient outcomes. This study aimed to identify factors influencing the prescription and non-prescription of metformin, the recommended first-line therapy in Western guidelines, and to evaluate whether these prescribing patterns align with evidence-based recommendations. It also explores factors associated with initial combination therapy, a more recent and controversial approach compared to stepwise therapy. We conducted a systematic search in PubMed, Scopus, and Web of Science on 25 August 2023, without language or time restrictions, to identify observational analytical studies assessing factors associated with the initiation of metformin or combination therapy in adults with type 2 diabetes mellitus who were naïve to antidiabetic medications. Studies involving pregnant or breastfeeding women were excluded. A narrative synthesis was conducted. Study quality was assessed using the Joanna Briggs Institute critical appraisal checklists (PROSPERO registration number CRD42023438313). Thirty studies were included, evaluating 105 variables, most of which (62%) were assessed in one study. The 25 variables using combination therapy as the outcome were mostly (72%) evaluated also in one study. Initial metformin prescription was strongly and positively associated with younger age, lower glycated haemoglobin levels, higher body mass index, and absence of renal impairment. Initial combination therapy was associated with higher HbA1c levels and a lower burden of comorbidities. Findings also highlighted a discrepancy between clinical practice and evidence-based recommendations. However, concerns were raised regarding both the internal and external validity of the included studies. Our systematic review, which offers insights into real-world clinical practices, indicated that there is a misalignment between clinical practices and evidence-based recommendations, supporting the need for interventions in this field.engClinical decision-makingCombination therapyFirst lineMetforminPrescribingType 2 diabetes mellitusresearch article10.3390/diabetology61001142673-4540