Abstract
Methods We retrospectively constructed database of 763 Japanese patients with T2DM and CKD who received sSGLT2is for more than 1 year. Among these SGLT2i-treated patients, 338 were receiving concomitant DPP4i (DPP4i group), and 99 were receiving concomitant GLP1Ra (GLP1Ra group). The two groups were compared using the propensity score matching method. Results In the matched model including 86 cases per group, the decrease in the logarithmic value of the ACR and rate of reduction in the estimated glomerular filtration rate (eGFR; mL/min/1.73 m2) of the GLP1Ra group showed no significant difference from those in the DPP4i group (−0.12 ± 0.48 vs. −0.13 ± 0.45 and −2.3 ± 18.5 vs. −6.2 ± 13.8, respectively, P = 0.10). However, the incidence of a >6.4% decrease in the eGFR was significantly lower in the GLP1Ra group than in the DPP4i group (35% vs. 52%, respectively, P = 0.03). The level of hemoglobin A1c (mmol/mol) after SGLT2i treatment was significantly lower in the DPP4i group than in the GLP1Ra group in the matched model (58.3 ± 11.8 and 62.7 ± 14.8, respectively, P = 0.02). Conclusion Among the SGLT2i-treated patients with T2DM and CKD, concomitant treatment with GLP1Ra has a marked improving effect on the change in the eGFR.
Highlights
Cardiovascular outcome trials (CVOTs) using empagliflozin (EMPA-REG OUTCOME trial) [1, 2], dapagliflozin (DECLARE-TIMI58) [3], and canagliflozin (CANVAS/ CANVAS-R) [4] have demonstrated improvements in cardiovascular and renal events
Our retrospective survey revealed the improvement in the urine Journal of Diabetes Research albumin-to-creatinine ratio (ACR) in Japanese patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in clinical practice [5]
dipeptidyl peptidase 4 inhibitor (DPP4i) failed to show superiority compared with placebo for reducing the incidence of major adverse cardiovascular events (MACEs) [6,7,8,9], but some types of GLP1Ra did show superiority for reducing the incidence of MACEs and improving renal composite outcomes [10,11,12,13]
Summary
Cardiovascular outcome trials (CVOTs) using empagliflozin (EMPA-REG OUTCOME trial) [1, 2], dapagliflozin (DECLARE-TIMI58) [3], and canagliflozin (CANVAS/ CANVAS-R) [4] have demonstrated improvements in cardiovascular and renal events. The incretin-related hypoglycemic agents; dipeptidyl peptidase 4 inhibitor (DPP4i) and glucagon-like peptide 1 agonist (GLP1Ra) were major concomitant medications, as they were administrated to more than 70% of SGLT2i-treated patients Both DPP4i and GLP1Ra are incretin-related drugs that reduce the plasma glucose level with an incretin effect, showing relatively similar results in CVOTs. DPP4i failed to show superiority compared with placebo for reducing the incidence of major adverse cardiovascular events (MACEs) [6,7,8,9], but some types of GLP1Ra did show superiority for reducing the incidence of MACEs and improving renal composite outcomes [10,11,12,13]. Among the SGLT2i-treated patients with T2DM and CKD, concomitant treatment with GLP1Ra has a marked improving effect on the change in the eGFR
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