OBJECTIVES: This is a protocol for a Cochrane review (intervention). The objectives are as follows: To assess the clinical benefits and adverse effects of glucagon-like peptide-1 receptor agonist-based regimens, compared with metformin-based glucose-lowering regimens, for preventing cardiovascular events including all-cause mortality, cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, and metabolic adverse events (including transient hypoglycemia) in adults with type 2 diabetes mellitus across primary and secondary prevention settings.