Comparison of metformin, dapagliflozin, and their combination in the management of Type 2 diabetes mellitus: A review

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder with a high global prevalence, including in Indonesia. Metformin is the most commonly used first-line therapy. However, disease progression often necessitates combination therapy. Dapagliflozin, an SGLT2 inhibitor, has been shown to reduce blood glucose levels and body weight. This review aims to compare the effectiveness, safety, and cost-effectiveness of metformin, dapagliflozin, and their combination in patients with T2DM. A literature search was conducted through PubMed, NCBI, and Google Scholar using relevant keywords. Inclusion criteria included publications from 2015 to 2025 that compared metformin, dapagliflozin, and their combination. Five studies meeting the criteria were analyzed to assess therapeutic effectiveness, safety, and cost-effectiveness. Combination therapy with dapagliflozin and metformin resulted in significantly greater reductions in HbA1c and body weight, as well as improvements in metabolic parameters, compared with monotherapy. The combination demonstrated a favorable safety profile, with a mild increase in urinary tract and genital infections that were generally well tolerated. Pharmacoeconomic analyses indicated that early initiation of combination therapy was more costeffective in the long term than a stepwise approach. Dapagliflozin–metformin combination therapy is more effective and cost-efficient than monotherapy for managing T2DM, with an acceptable safety profile. This regimen may be considered as an alternative for patients who do not achieve glycaemic targets with monotherapy.