Comparative effectiveness of combining antidiabetic medications to treat renal impairment in patients with type 2 diabetes mellitus

The comparative renoprotective effects of metformin-GLP-1 RA (glucagon-like peptide 1 receptor agonist), metformin-DPP-4i (dipeptidyl peptidase 4 inhibitor) and metformin-oADM (other antidiabetes medication) in patients with DKD (diabetic kidney disease) were evaluated by assessing the associations between renal impairment and combination therapies. Patients initially diagnosed with DKD between January 1, 2010, and January 1, 2017, were included. Those receiving combination treatment with metformin-GLP-1 RA, metformin-DPP-4i, or metformin-oADM were selected and paired. A logistic regression model was applied to generate odds ratios with 95% confidence intervals to assess the associations between the composite renal impairment outcomes and the combination ADM (antidiabetes medication) groups. Sensitivity analyses were also performed. Renal impairment was significantly reduced in patients who were treated with metformin-GLP-1 RA than in those treated with metformin-DPP-4i in the primary and secondary analyses (OR 0.60, P < 0.05 for the primary outcome; OR 0.44, P < 0.05 for the secondary outcome). The associations of renal impairment risk and ADM combination therapies with metformin-DPP-4i versus metformin-oADM were not statistically significant in either the primary or secondary analysis (OR = 1.22, P = 0.20 for the primary outcome; OR = 0.90, P = 0.53 for the secondary outcome). The results of the sensitivity analyses were consistent with those of the main analysis. The combination metformin-GLP-1 RA was associated with fewer renal impairment events compared to metformin-DPP-4i and metformin-oADM, indicating potential additive or synergistic effects within the combination metformin-GLP-1 RA group. Metformin-DPP-4i did not significantly improve renal impairment outcomes in this study.