(CSPOT53) Comparison of Anemia Outcomes between SGLT2 Inhibitors and GLP-1 Receptor Agonists in Diabetic Patients with Chronic Kidney Disease: Multi-institutional Cohort Study with Target Trial Emulation in Taiwan

Background: Studies from post-hoc analyses of the CREDENCE and DAPA-CKD trials suggest a reduced risk of anemia with the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors. However, the broader applicability of these findings to the general population of patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD), as well as their effectiveness in real-world clinical settings compared to current treatments, remains to be determined.

Objectives: To evaluate the incidence of anemia in patients with T2DM and CKD stages 1-3, who are treated with either SGLT2 inhibitors or glucagon-like peptide-1 receptor agonists (GLP-1 RAs).

Methods: We conducted the retrospective cohort study with target trial emulation framework of the CREDENCE and DAPA-CKD trials by analyzing the largest multi-institutional electronic medical records database in Taiwan, 2016-2022. We included adults with T2DM and CKD stages 1-3 initiating SGLT2 inhibitors or GLP-1 RAs. The primary outcome was a composite of anemia outcomes, including anemia event occurrence (hemoglobin level < 12-13 g/dl or ICD-10-CM diagnosis codes) or anemia treatment initiation. We also evaluated changes in hematological parameters, including hemoglobin, hematocrit and red blood cell count, during the follow-up period up to three years.

Results: We included a total of 13,799 patients with T2DM and CKD, initiating SGLT2 inhibitors (n=12,331, mean age: 62.4±12.3 years) or GLP-1 RAs (n=1,468, mean age: 61.5±13.3 years). After the median follow-up period of 2.5 years, patients treated with SGLT2 inhibitors showed a reduced incidence of composite anemia outcomes (HR: 0.81, 95% CI: 0.73-0.90), compared to those on GLP-1 RAs. In terms of specific anemia outcomes, SGLT2 inhibitors were associated with a decreased anemia event occurrence (HR: 0.79, 95% CI: 0.71-0.87), although they did not significantly lower the initiation of anemia treatment (HR: 0.99, 95% CI: 0.83-1.19). The hematological parameter changes over a 3-year follow-up for both SGLT2 inhibitors and GLP-1 RAs reinforced these findings.

Conclusions: SGLT2 inhibitors were associated with reduced risk of composite anemia outcomes, particularly in the incidenceof anemia events. SGLT2 inhibitors could potentially be used as supplementary treatment to lower the incidence of anemia in patients with T2DM and CKD.