OBJECTIVES: This study aimed to perform a comparative analysis of the efficacy in metabolic control of modern oral antidiabetics through a systematic literature review and a network meta-analysis.

METHODS: A systematic literature review was conducted to identify clinical evidence of oral semaglutide (14 mg once daily), dipeptidyl peptidase-4 inhibitors (DPP4i), sodium-glucose cotransporter-2 inhibitors (iSGLT2) and the combination SGLT2i + DPP4i in adults with Type 2 Diabetes (T2D) who cannot be controlled with metformin monotherapy. Eligible studies had a follow-up between 48 to 56 weeks. Subsequently, the evidence was evaluated according to the quality of the studies. Four efficacy outcomes were subject to network meta-analysis under a Bayesian approach, comparing the evaluated interventions: achievement of glycated hemoglobin (HbA1c) target of <7%, HbA1c % change from baseline, change in fasting glycemia from baseline and change in body weight (kg) from baseline.

RESULTS: Oral semaglutide had the best performance in the endpoint of body weight reduction, (mean difference: -0.66 kg; 95% CI: -1.29, -0.08) vs. the SGLT2i + DPP4i combination. Only DPP4i was not superior to placebo regarding this outcome (mean difference: -0.13 kg; 95% CI: -0.23, 0.49). Furthermore, oral semaglutide and the SGLT2i + DPP4i combination showed comparable efficacy results in the endpoints of HbA1C net change (mean difference: 0.02; 95% CI: -0.77, 0.80) from baseline, the chance of achieving an HbA1c target of <7% (relative risk: 1.07; 95% CI: 0.57, 1.99) and in the change in fasting glucose levels (mean difference: 9.30 mg/dL; 95% CI: -4.94, 26.54).

CONCLUSIONS: Our results suggest that oral semaglutide could be used as an alternative to the SGLT2i + DPP4i combination for the metabolic control of T2D patients. Additionally, oral semaglutide should be considered in overweight or obese T2D patients who require weight reduction.