Kidney outcomes with SGLT2 inhibitor versus DPP4 inhibitor use in older adults with diabetes

Abstract

Background: While the kidney-protective effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors have attracted much attention, there are limited real-world clinical data examining the effects of SGLT2 inhibitors on kidney function in older individuals. We aimed to compare the kidney outcomes between SGLT2 inhibitor and dipeptidyl peptidase 4 (DPP4) inhibitor use in older adults with diabetes.

Methods: Using a nationwide claims database, we studied 6354 older adults (≥60 years of age) who had diabetes and were newly initiated on SGLT2 inhibitors or DPP4 inhibitors. A 1:4 propensity score matching algorithm was used to compare changes in estimated glomerular filtration rate (eGFR) between SGLT2 inhibitor and DPP4 inhibitor users. The primary outcome was a decrease in the rate of eGFR, which was obtained using a linear mixed-effects model with an unstructured covariance.

Results: Following propensity score matching, 6354 individuals including 1271 SGLT2 inhibitor users and 5083 DPP4 inhibitor users {median age 68 years [interquartile range (IQR) 65-70], male 60.4%, median eGFR 69.0 ml/min/1.73 m2 [IQR 59.1-79.0], median haemoglobin A1c [HbA1c] 6.9% [IQR 6.5-7.4]} were analysed. SGLT2 inhibitor users had a slower eGFR decline than did DPP4 inhibitor users [-0.97 ml/min/1.73 m2/year (95% CI -1.24 to -0.70) versus -1.83 ml/min/1.73 m2/year (95% CI -1.97 to -1.69); P for interaction <.001]. This finding remained consistent across subgroups based on age, sex, body mass index, HbA1c level, renin-angiotensin system inhibitor use and baseline eGFR. Additionally, the risk of a ≥20%, ≥30% and ≥40% decrease in eGFR from baseline was significantly lower in SGLT2 inhibitor users than in DPP4 inhibitor users.

Conclusions: Our analysis, utilizing a nationwide epidemiological dataset, demonstrated that the decrease in eGFR was slower in individuals ≥60 years of age with diabetes who were prescribed SGLT2 inhibitors compared with those prescribed DPP4 inhibitors, suggesting a potential advantage of SGLT2 inhibitors for kidney outcomes even in older individuals with diabetes.

Keywords: SGLT2 inhibitors; chronic kidney disease; diabetes; epidemiology.

Graphical Abstract

Figure 1:

Change in eGFR among SGLT2 inhibitor and DPP4 inhibitor users. We used a linear mixed-effects model to compare changes in eGFR between SGLT2 inhibitor and DPP4 inhibitor users. The model included the treatment group (SGLT2 inhibitor or DPP4 inhibitor users), time and the interaction term between the treatment group and time as fixed effects. Error bars represent 95% CIs.

Figure 2:

The annual change in eGFR among SGLT2 inhibitor and DPP4 inhibitor users. We used a linear mixed-effects model to compare the annual changes in eGFR between SGLT2 inhibitor and DPP4 inhibitor users. The model included the treatment group (SGLT2 inhibitor or DPP4 inhibitor users), time and the interaction term between the treatment group and time as fixed effects. Error bars represent 95% CIs.

Figure 3:

Subgroup analysis. Subgroup analysis was performed based on median age (≥69 and <69 years), sex (male and female), median BMI (≥24.5 and <24.5 kg/m²), HbA1c (≥7.5 and <7.5%), the use of RAS inhibitors (with and without), proteinuria [negative (negative and trace) and positive (1+, 2+ and 3+)] and eGFR (≥60 and <60 ml/min/1.73 m²). Error bars represent 95% CIs.