Use of SGLT2 Inhibitors vs GLP-1 RAs and Anemia in Patients With Diabetes and CKD

Abstract

Importance: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are associated with lower anemia risk, based on findings from post hoc analyses of the CREDENCE and DAPA-CKD trials; however, the effectiveness of SGLT2 inhibitors in a more generalizable type 2 diabetes (T2D) and chronic kidney disease (CKD) population, with active comparisons pertinent to current practice, is unknown.

Objective: To evaluate and compare anemia incidence between SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) among patients with T2D and CKD stages 1 to 3.

Design, setting, and participants: This retrospective cohort study used target trial emulation of an expanded CREDENCE and DAPA-CKD study framework. The study was conducted among adults with T2D and CKD initiating SGLT2 inhibitors or GLP-1 RAs between January 1, 2016, and December 31, 2021, with follow-up until December 31, 2022. The study was conducted at the Chang Gung Medical Foundation, the largest multi-institutional hospital system in Taiwan.

Exposures: Initiation of SGLT2 inhibitors or GLP-1 RAs.

Main outcomes and measures: The primary outcome was a composite of anemia outcomes, including anemia event occurrence (hemoglobin level <12-13 g/dL or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes) or anemia treatment initiation. Changes in hematological parameters, including hemoglobin level, hematocrit level, and red blood cell count, were evaluated during the follow-up period for as long as 3 years.

Results: The cohort included a total of 13 799 patients with T2D and CKD, initiating SGLT2 inhibitors (12 331 patients; mean [SD] age, 62.4 [12.3] years; 7548 [61.2%] male) or GLP-1 RAs (1468 patients; mean [SD] age, 61.5 [13.3] years; 900 [61.3%] male). After the median follow-up period of 2.5 years, patients receiving SGLT2 inhibitors had lower incidence of composite anemia outcomes (hazard ratio [HR], 0.81; 95% CI, 0.73-0.90) compared with those receiving GLP-1 RAs. SGLT2 inhibitors were associated with a lower incidence of anemia events (HR, 0.79; 95% CI, 0.71-0.87) but not with a lower rate of anemia treatment initiation (HR, 0.99; 95% CI, 0.83-1.19). Changes in hematological parameters for SGLT2 inhibitors and GLP-1 RAs throughout the 3-year follow-up period supported the primary analyses.

Conclusions and relevance: In this multi-institutional cohort study with target trial emulation, SGLT2 inhibitors were associated with a decreased risk of composite anemia outcomes, especially anemia event occurrences. SGLT2 inhibitors may be considered as an adjunct therapy to reduce anemia incidence in patients with T2D and CKD.

Figure 1.. Patient Selection Flowchart

To convert hemoglobin to grams per liter, multiply by 10; hemoglobin A_1c (HbA_1c) to proportion of total hemoglobin, multiply by 0.01; potassium to millimoles per liter, multiply by 1. ALT indicates alanine transaminase; CGRD, Chang Gung Research Database; CKD, chronic kidney disease; ESAs, erythropoiesis-stimulating agents; GLP-1 RAs, glucagon-like peptide-1 receptor agonists; PAOD, peripheral arterial occlusion disease; RBC, red blood cell; SGLT2, sodium-glucose cotransporter 2; T1D, type 1 diabetes; T2D, type 2 diabetes; UACR, urine albumin-to-creatinine ratio; ULN, upper limit of normal. ^aPatients could have met multiple exclusion criteria.

Figure 2.. Composite Anemia Outcomes of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) After Applying Propensity-Score Fine Stratification Weights

Incidence rates (IRs) are presented per 100 person-years. To convert hemoglobin to grams per liter, multiply by 10. ESA indicates erythropoiesis-stimulating agents; HR, hazard ratio; ICD-10-CM, International Classification of Diseases, 10th Revision, Clinical Modification; RBC, red blood cell.