#3178 effects of sglt-2 inhibitors versus dpp-4 inhibitors on anemia in patients with type 2 diabetes

Abstract Background and Aims The number of people suffering from diabetes has exceeded 400 million worldwide. The incidence of anemia in type 2 diabetes mellitus (T2D) patients is about twice that of non-diabetic patients. Moreover, patients with T2D who have chronic kidney disease are at higher risk of developing anemia and it also occurs earlier. Therefore it is worth investigating the problem of anemia in T2D patients. This study was conducted to compare the effects of the new oral hypoglycemic agents (sodium-glucose cotransporter-2 inhibitors, SGLT-2i and dipeptidyl peptidase-4 inhibitors, DPP-4i) on anemia in patients with T2D. Method This study was designed as a retrospective cohort study and analyzed using the Kaohsiung Medical University Hospital Research Database (KMUHRD). Study inclusion criteria: (1) patients start using SGLT-2i or DPP-4i from January 1, 2015 to December 31, 2020 (first prescription is defined as not used within 180 days prior to the activation date, and cases are screened from the year prior to the starting intake date), and (2) patients with T2D who meet the diagnosis of anemia (according to the World Health Organization definition of hemoglobin <13 g/ dL in men and <12 g/ dL in women) at the time of initial dosing. Patients without hemoglobin data within 180 days before and after treatment were excluded. The outcome will evaluate the effect of SGLT-2i and DPP-4i on erythropoietic parameters including erythrocyte, reticulocyte count, hemoglobin, and hematocrit. Results In total 4,555 patients were enrolled in this study. Of these patients, 4,251 were treated with DPP-4i and 304 with SGLT-2i. Using propensity score matching, 303 patients each from the DPP-4i and SGLT-2i groups were selected based on patient characteristics. There were no difference in hemoglobin values (Median: 11.30 vs. 11.20 g/ dL, P = 0.328) and renal function (expressed as eGFR, 83.30 vs. 81.84 mL/min, P = 0.255) between the DPP-4i and SGLT-2i groups before treatment. After six months of follow-up, only the SGLT-2i group showed a statistically significant increase in erythrocyte count (3.88 to 4.19 × 10^6/uL, P < 0.001), hemoglobin (11.20 to 11.70 g/ dL, P < 0.001), and hematocrit values (34.4 to 36.5%, P < 0.001). However, the same changes were not observed in the DPP-4i group: erythrocyte count (3.87 to 3.91 × 10^6/uL, P = 0.051), hemoglobin (11.30 to 11.40 g/ dL, P = 0.315), and hematocrit values (34.4 to 34.7%, P = 0.102). The Δhemoglobin showed a significant correlation with the SGLT-2i use, metformin use, erythrocyte count, hematocrit, hemoglobin and eGFR levels at baseline. Multiple regression analyses showed that use of SGLT-2i might be the main influencing factor. Conclusion Our study compared the effects of SGLT-2i and DPP-4i on erythropoietic parameters in T2D patients, and only the SGLT-2i group showed significant increase in erythrocyte count, hemoglobin, and hematocrit. The use of SGLT-2i may be the major factor affecting the improvement of erythropoietic parameters. Therefore the hypoglycemic effect of SGLT-2i may be accompanied by the improvement of anemia.