GLP1R and type 2 diabetes mellitus: Justification. A major body of evidence from randomized controlled trials supports the use of metformin, SGLT-2 inhibitors, or GLP-1 receptor agonists as first-line treatment in patients with type 2 diabetes due to relevant efficacy in reducing HbA1c without increasing the risk of hypoglycemia and less risk of MACE and all-cause mortality.