Background/Objective: SGLT2 inhibitors (SGLT2i) and GLP1 receptor agonists (GLP1Ra) have already shown evidence of cardiovascular and renal outcomes; therefore, combination therapy with these drugs is now of interest in clinical practice for the management of type 2 diabetes mellitus (T2DM). However, there are few reports on the effect of combination therapy on renal functions. This study aimed to investigate the effect of combination therapy on renal functions.

Methods: We retrospectively extracted data of patients with T2DM who had received both SGLT2i and GLP1Ra treatment for at least 1-year at 18 medical facilities in Japan. Finally, 341 patients in the GLP1Ra-preceding group and 319 in the SGLT2i-preceding group were analyzed. The multiple imputation method was adopted for missing values, and propensity score (PS) matching with the algorithm of 1:1, neighbor match, and no replacement, was performed for comparison between the two groups.

Result: In each group, 152 patients were matched. On the matched model, mean observational period was 54 months. Regarding the annual change in eGFR (mL/min/m2/year) before and after combination treatment, the SGLT2i-preceding group showed a significant increase from -3.76±10.48 to 0.04±6.29 (p=0.002), whereas the GLP1Ra-preceding group showed no significant change from -2.09±13.44 to -1.97±6.16. The logarithmic value of urine albumin-to-creatinine ratio at the time of the initiation of either drug, at the time of the initiation of combination treatment, and after the combination treatment, were 3.77±1.63, 3.83±2.21, 3.73±1.80 in GLP1Ra-preceding group, and 3.65±20.4, 3.56±1.29, 3.75±0.91 in SGLT2i-preceding group, respectively, and there was no significant difference among two groups. Conclusion: The addition of GLP1Ra to SGLT2i-treated patients significantly improved the annual change in eGFR. The renal benefits by combination therapy with SGLT2i and GLP1Ra may be affected by preceding drug.


M.Toyoda: None. K.Kobayashi: None.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at