OBJECTIVES: This study aims to utilize Bayesian network meta-analysis (NMA) to assess the relative efficacy of dapagliflozin add-on to metformin as a dual therapeutic strategy for managing T2DM. The main emphasis is on comparing the outcomes of this dual therapy approach with both placebo and other SGLT2 inhibitors used in combination with metformin.

METHODS: A Bayesian NMA with random effects model has been conducted to estimate the relative efficacy of dapagliflozin when administered at various doses and frequencies in combination with metformin. Pertinent data related to changes in HbA1c levels from the baseline were extracted for analysis. The assessment of relative efficacy was conducted by evaluating the mean differences (MD).

RESULTS: Following a systematic review of the existing body of literature, the study encompassed a selection of 20 randomized controlled trials, all of which provided outcomes for a minimum duration of 16 weeks. The reduction in HbA1c levels demonstrated a significant increase when dapagliflozin at doses of 2.5mg QD, 5mg QD, and 10mg QD was administered alongside metformin, as compared to the combination of metformin with a placebo. The mean difference between the three treatment regimens compared to placebo were -0.388 (-0.625, -0.158), -0.507 (-0.682, -0.340) and -0.523 (-0.683, -0.382). However, no statistically significant difference was observed in the efficacy endpoint of HbA1c reduction compared with other SGLT2 combined with metformin.

CONCLUSIONS: This study synthesized direct and indirect evidence to establish indirect comparisons of dual therapy combinations of different SGLT2 inhibitors and metformin. The result indicates that irrespective of the medication's dosage and frequency, the therapeutic impact of dapagliflozin in conjunction with metformin exhibited a considerably superior efficacy compared to metformin as a standalone treatment. The variance in effectiveness among distinct SGLT2 and metformin regimens may be discernible in facets beyond HbA1c.