Background: It has been reported that the combination therapy of Glucagon-like peptide-1 receptor agonists (GLP-1RA) and Sodium-glucose Cotransporter 2 Inhibitors (SGLT2i) decrease micro-albuminuria in type 2 diabetes (T2DM) with nephropathy. There is the possibility that protective effects on estimate glomerular filtration rate (eGFR) and micro-albuminuria are different between (1) GLP-1RA add-on therapy to SGLT2i and (2) SGLT2i to GLP-1RA.

Objective: In this study, we aimed to clarify whether there are differences in the changes of eGFR and micro-albuminuria depending on the order of combination therapy between (1) and (2) in T2DM.

Method: We studied 69 patients with T2DM who took GLP-1RA together with SGLT2i in Our Hospital, retrospectively. We investigated urine albumin to creatinine ratio (ACR), eGFR, body mass index (BMI), systolic blood pressure (SBP), HbA1c, UA, Na, Cl, hematocrit (Ht) and platelet (Plt) before and after six months of the therapy. Six months changes (delta:Δ) of clinical parameters were compared between each combination therapy.

Result: In all subjects, HbA1c, BMI and logACR were significantly decreased with the therapies, respectively. As the comparison of Δ in each clinical factors between (1) and (2) groups, ΔHbA1c of (1) significantly showed lower levels than (2). Whereas ΔNa and ΔCl of (1) significantly showed higher levels. Multiple regression analysis including ΔPlt, ΔHt, ΔUA, ΔBMI, ΔHbA1c, and the type of combination therapy as an independent factor for eGFR, ΔUA, ΔHt and ΔHbA1c were the significant contributing factors. Multiple regression analysis including ΔBMI, ΔHDL-C, ΔHbA1c, age, sex and the type of combination therapy as an independent factor for ΔlogACR, ΔHDL-C was the significant contributing factor. The type of combination therapy was not shown as a significant associated factor for ΔlogACR.

Conclusions: Both GLP-1RA add-on therapy to SGLT2i and SGLT2i to GLP-1RA equally reduce albuminuria in T2DM with nephropathy.


M. Ohara: None. K. Motoyama: None. A. Tamai: None. T. Sakura: None. Y. Yakushiji: None. M. Hosoi: Speaker's Bureau; Self; Eli Lilly and Company.

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