Sodium‐glucose co‐transporter 2 inhibitors and hematopoiesis

Abstract

Many patients with diabetes mellitus, especially those with chronic kidney disorders, have some degree of anemia due to a spectrum of causes and underlying pathophysiologic pathways. As such, enhancement in erythropoiesis is important in these patients. Sodium‐glucose cotransporter 2 inhibitors (SGLT2i) are a relatively new class of antidiabetic drugs with confirmed protective effects in kidney and cardiovascular tissues. Recent evidence suggests that these drugs may provide additional benefits in enhancing hematopoietic processes in diabetic patients. Though the exact mediating pathways have not been fully elucidated, cellular mechanisms are likely involved. In the current study, we present the potential pathways by which SGLT2i may modulate hematopoiesis and stimulate erythropoiesis.

New insights into cellular links between sodium–glucose cotransporter‐2 inhibitors and ketogenesis

“…48,49 5 | SGLT2is AND KETOACIDOSIS While SGLT2is lower blood glucose by blocking glucose reabsorption and inducing overt glycosuria, 30 this may be accompanied by increased ketone body generation. 21,50 In a large clinical study of 208 757 new users of SGLT2is, SGLT2i therapy was associated with an almost threefold increased risk for DKA in diabetic patients. 50 A separate study demonstrated that SGLT2i therapy was associated with more than a twofold increase in DKA relative to DPP4 inhibitors (4.9 events vs. 2.3 events per 1000 patients/year) in diabetic patients.…”

“…12 Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are a class of potent antidiabetes agents that effectively reduce blood glucose via inducing overt glycosuria and natriuresis 13,14 and also exert several pleiotropic actions. 15,20,21 Some recent reports, however, suggest that SGLT2is may induce and/or modulate DKA. 22,23 Therefore, in this current review, we present the latest findings concerning possible interactions between SGLT2i therapies and DKA.…”

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

“…Recently, 2 post hoc analyses of the CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trials have suggested additional benefits regarding anemia-related outcomes from canagliflozin and dapagliflozin treatment . Although the exact mechanism behind these findings remains underinvestigated, SGLT2 inhibitors appear linked to increases in erythropoietin (EPO) production, contributing to increased oxygen delivery to the kidney and decreased kidney hypoxia …”

Erythropoiesis and estimated fluid volume regulation following initiation of ipragliflozin treatment in patients with type 2 diabetes mellitus and chronic kidney disease: A post‐hoc analysis of the PROCEED trial

“…These findings suggest that increased haemoglobin and haematocrit levels per se or enhancement of mediating pathways involved in increasing these parameters, after initiation of SGLT2 inhibitor treatment, improve CV and renal outcomes. The exact mechanisms by which SGLT2 inhibitors increase haemoglobin and haematocrit levels are unclear; however, these effects might be attributed to the enhancement of erythropoiesis, rather than haemoconcentration resulting from the diuretic effect of SGLT2 inhibitors 6–8 . Several clinical studies have shown that the increase in serum concentrations of erythropoietin (EPO), a hormone produced in the kidney that is essential for erythropoiesis, was followed by an increase in haemoglobin and haematocrit levels, after initiation of SGLT2 inhibitor treatment in patients with heart failure, type 2 diabetes mellitus (T2DM), and patients with T2DM who had a history of coronary artery disease 9–13 .…”