SGLT2 Inhibitor Use Lowers Anemia Risk in Patients with Diabetes, CKD

Shih-Chieh Shao, RPh, PhD

Credit: ResearchGate

Sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment may reduce the incidence of anemia among patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) stages 1 to 3, according to new research.¹

Across nearly 14,000 individuals with T2D and CKD, the initiation of SGLT2 inhibition was linked to a 19% decrease in incident anemia risk compared with treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RA).

“These main findings were supported by changes in hematological laboratory parameters, which showed significant differences between the SGLT2 inhibitor and GLP-1 RA groups throughout the 3-year follow-up,” wrote the investigative team, led by Shih-Chieh Shao, RPh, PhD, department of pharmacy, Keelung Chang Gung Memorial Hospital.

Anemia is common among patients with T2D and CKD and has an association with higher mortality and poorer health-related quality of life.² Clinical guidelines, however, do not offer specific recommendations for adjuvant therapy to prevent anemia. SGLT2 inhibitor and GLP-1 RA use are recommended for patients with T2D and CKD to help achieve their glycemic goals and mitigate anemia-related risk.³

Two recent post hoc analyses of the CREDENCE and DAPA-CKD trials demonstrated additional benefits in anemia-related outcomes from the SGLT2 inhibitors, canagliflozin and dapagliflozin, respectively.⁴ However, Shao and colleagues noted limitations in the trials could have reduced their relevance for clinical practice, whether the effects on anemia were independent of glycemic control and kidney function improvement after treatment with SGLT2s.¹

For this multi-institutional cohort study, emulating the CREDENCE and DAPA-CKD study framework, the team evaluated anemia incidence associated with the initiation of SGLT2 inhibitors, compared with GLP-1 RA, in patients with T2D and CKD stages 1 to 3.

Analysis occurred in the Chang Gung Research Database, involving electronic medical records from Taiwan’s largest healthcare system. Individuals with T2D and CKD (≥18 years old; hemoglobin A1c (HbA1c) ≥6.5%) initiating SGLT2 inhibitors or GLP-1 RA between January 2016 and December 2021 were included for analysis.

Empagliflozin, dapagliflozin, canagliflozin, and ertugliflozin were included as the SGLT2 inhibitor exposure group, while lixisenatide, liraglutide, dulaglutide, and semaglutide were identified as the GLP-1 RA comparison groups. The analysis’ primary end point was a composite of anemia outcomes, including incident anemia event occurrence or the initiation of anemia treatments, including oral or parenteral iron preparations.

Among 13,799 patients with T2D and CKD in the study cohort, 12,331 (89.4%) initiated SGLT2 inhibitors (mean age, 62.4 years; 7548 [61.2%] male) and 1468 received GLP-1 RAs (mean age, 61.5 years; 900 [61.3%] male). During the median follow-up of 2.5 years, investigators observed 2887 and 429 composite anemia outcomes in the SGLT2 inhibitor and GLP-1 RA groups, respectively.

The incident ratio of composite outcomes was lower in those receiving SGLT2 inhibitors (8.33 per 100 person-years) than those receiving GLP-1 RAs (10.20 per 100 person-years), for a hazard ratio (HR) of 0.81 (95% CI, 0.73 - 0.90). Moreover, SGLT2 inhibitor treatment exhibited a lower incidence of anemia events (HR, 0.79; 95% CI, 0.71 - 0.87), but not lower initiation of anemia treatment (HR, 0.99; 95% CI, 0.83 - 1.19).

The analysis also measured the changes in hematological parameters, including hemoglobin hematocrit levels, and red blood cell count, during the follow-up period for up to 3 years. Shao and colleagues found the hematological parameters remained unchanged in the SLGT2 inhibitor group and decreased in the GLP-1 RA group across the 3-year follow-up period.

In citing this observed lower risk of anemia, Shao and colleagues estimated the number needed to treat the composite anemia outcome at 55. Based on this estimation, a single additional composite anemia outcome may be preventable among every 55 patients with T2D and CKD who initiate SGLT2 inhibitors, compared with GLP-1 RAs.

“More importantly, the findings were consistent across different individual SGLT2 inhibitors, suggesting a class effect of anemia benefits from SGLT2 inhibitors,” Shao and colleagues wrote.

References

1. _{Hu J, Shao S, Tsai DH, Chuang AT, Liu K, Lai EC. Use of SGLT2 Inhibitors vs GLP-1 RAs and Anemia in Patients With Diabetes and CKD. JAMA Netw Open. 2024;7(3):e240946. doi:10.1001/jamanetworkopen.2024.0946}
2. _{Brière M, Diedisheim M, Dehghani L, Dubois-Laforgue D, Larger E. Anaemia and its risk factors and association with treatments in patients with diabetes: A cross-sectional study. Diabetes Metab. 2021;47(1):101164. doi:10.1016/j.diabet.2020.05.006}
3. _{de Boer IH, Khunti K, Sadusky T, et al. Diabetes Management in Chronic Kidney Disease: A Consensus Report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO). Diabetes Care. 2022;45(12):3075-3090. doi:10.2337/dci22-0027}
4. _{Koshino A, Schechter M, Chertow GM, et al. Dapagliflozin and Anemia in Patients with Chronic Kidney Disease. NEJM Evid. 2023;2(6):EVIDoa2300049. doi:10.1056/EVIDoa2300049}