Comparative effectiveness of metformin and alogliptin combination therapy versus metformin monotherapy in patients with type 2 diabetes: an emulated target trial.

BACKGROUND: As type 2 diabetes mellitus (T2DM) has emerged as a global health challenge, various treatment strategies, such as the use of metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors, have been widely adopted. However, evidence on the effectiveness of their combination therapy remains limited, particularly in studies utilizing target trial emulation approaches within the South Korean population. METHODS: This emulated target trial included 68,372 patients with T2DM identified between 2001 and 2024 from four university hospitals in South Korea. After applying exclusion criteria, patients were classified into two groups: metformin monotherapy and metformin plus alogliptin dual therapy. A 1:2 propensity score matching approach was used to balance baseline covariates between groups. The outcome of this analysis was the achievement of glycemic control, defined as haemoglobin A1c (HbA1c) < 6.5% during the follow-up period. Clinical parameters, including glycemic indices, were assessed over 24 weeks from the initiation of therapy using unpaired t-tests. Cox proportional hazards models were employed to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) to evaluate the likelihood of achieving glycemic control. RESULTS: After applying exclusion criteria and performing 1:2 propensity score matching, 1230 patients were included in the final analysis (371 in the dual therapy group and 662 in the monotherapy group). Over the 24-week follow-up period, the dual therapy group showed greater reductions in HbA1c and fasting plasma glucose, with the greatest improvement observed at 8 weeks. No significant differences were found between groups in changes across other clinical parameters. Although the reduction in HbA1c during 24-week follow-up period was greater in the dual therapy group, the difference did not reach statistical significance. However, over the extended follow-up period, patients receiving dual therapy exhibited a higher likelihood of achieving glycemic control (HbA1c < 6.5%) compared to those on monotherapy (aHR, 2.41; 95% CI, 1.64-3.55). CONCLUSION: By emulating a target trial, this study showed that dual therapy with metformin and alogliptin improved glycemic control in patients with T2DM in South Korea. Given the growing number of available treatment regimens, future research should incorporate a wider range of antidiabetic agents and explore the effectiveness of various therapeutic combinations. CLINICAL TRIAL NUMBER: Not applicable.