Comparative renal outcomes of matched cohorts of patients with type 2 diabetes receiving SGLT2 inhibitors or GLP-1 receptor agonists under routine care

Abstract

Aims/hypothesis: We compared the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) on renal outcomes in individuals with type 2 diabetes, focusing on the changes in eGFR and albuminuria.

Methods: This was a multicentre retrospective observational study on new users of diabetes medications. Participant characteristics were assessed before and after propensity score matching. The primary endpoint, change in eGFR, was analysed using mixed-effects models. Secondary endpoints included categorical eGFR-based outcomes and changes in albuminuria. Subgroup and sensitivity analyses were performed to assess robustness of the findings.

Results: After matching, 5701 participants/group were included. Participants were predominantly male, aged 61 years, with a 10 year duration of diabetes, a baseline HbA_1c of 64 mmol/mol (8.0%) and BMI of 33 kg/m². Chronic kidney disease (CKD) was present in 23% of participants. During a median of 2.1 years, from a baseline of 87 ml/min per 1.73 m², eGFR remained higher in the SGLT2i group compared with the GLP-1RA group throughout the observation period by 1.2 ml/min per 1.73 m². No differences were detected in albuminuria change. The SGLT2i group exhibited lower rates of worsening CKD class and favourable changes in BP compared with the GLP-1RA group, despite lesser HbA_1c decline. SGLT2i also reduced eGFR decline better than GLP-1RA in participants without baseline CKD.

Conclusions/interpretation: In individuals with type 2 diabetes, treatment with SGLT2i was associated with better preservation of renal function compared with GLP-1RA, as evidenced by slower decline in eGFR. These findings reinforce SGLT2i as preferred agents for renal protection in this patient population.

Keywords: Kidney disease; Obesity; Pharmacoepidemiology; Real-world; Type 2 diabetes.

Fig. 1

Study flow chart

Fig. 2

Major kidney outcomes. (a) Change in eGFR (primary outcome) in the two groups (^a54 months). The table shows the number of patients contributing with values to the model. (b) Total and chronic eGFR slopes. (c, d) Kaplan–Meier curves for the worsening of CKD class (c) and creatinine doubling (≥57% reduction in eGFR) (d). The tables show the number of patients at risk. (e) Forest plot of kidney outcomes in the ITT population. Tabular results are presented as crude rates in each group, HRs and 95% CIs along with their p values

Fig. 3

Intermediate endpoints. The change over time in HbA_1c (a), body weight (b), systolic BP (c) and diastolic BP (d) is shown for the two groups and compared using the MMRM. The tables show the number of patients contributing with values at each time point of the model. ^a54 months. DBP, diastolic BP; SBP, systolic BP

Fig. 4

Subgroup analysis. The primary endpoint (change in eGFR) was computed for each stratum of the initial population and compared between the SGLT2i and GLP-1RA groups. Nominal p values are shown (*significant after adjusting with Bonferroni correction)