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BOSTON -- The SGLT-2 inhibitor dapagliflozin (Farxiga) was tied to a suppression in plasma hepcidin concentrations in patients with type 2 diabetes, researchers reported here.

Compared with baseline, patients on 12 weeks of daily dapagliflozin (10 mg) experienced a significant reduction in plasma hepcidin (265 ng/mL to 215 ng/mL, P<0.05), according to Husam Ghanim, PhD, of the University of Buffalo School of Medicine in New York, and colleagues, in a presentation at the American Association of Clinical Endocrinologists (AACE) annual meeting.

Interim results from the ongoing analysis also found significant changes in several other clinical measures seen in patients on dapagliflozin treatment from baseline to 12 weeks, which were not seen among the placebo group (P<0.05 for all):

• Drop in HbA1c: 7.1% to 6.7%
• Increase in hemoglobin concentration: 13.2 g/dL to 13.8 g/dL
• Increase in hematocrit: 40.2% to 41.9%

Ferroportin, however, remained unchanged in the dapagliflozin group through the treatment phase.

"We have shown that dapagliflozin for 12 weeks in type 2 diabetics reduced hepcidin and increased transferrin and transferrin receptors," Ghanim stated. "The mechanisms that involves iron transport [are] all are upregulated, which basically allows and facilitates for more iron to be available for erythropoiesis. This effect is at multiple levels -- at the cellular levels, circulation, as well as the receptor level."

A total of 22 patients (mean age 62.1) are participating in the single center, double-blind study, all of whom have type 2 diabetes, obesity, and normal renal functioning. Individuals were excluded for current use of GLP-1 receptor agonists or SGLT-2 inhibitors. However, patients were allowed if they were on stable doses of statin, thiazolidinediones, ACE inhibitors, angiotensin II receptor blockers, and antioxidants.

Participants randomized into the dapagliflozin group receiving a starting dose of 5 mg daily and was then titrated up to 10 mg per day within the first week. Fasting blood samples were drawn and analyzed at baseline, and weeks 1, 6, and 12 of treatment.

The findings of this study may hold valuable implications for clinical practice, even in emergency situations, Ghanim suggested.

"In addition, we could also postulate that because of this action of SGLT-2 inhibitors and hematocrit and hemoglobin, there is more oxygenated blood that is available to tissues, especially in crisis time like myocardial infarction, which may explain the beneficial effects of SGLT-2's on cardiovascular disease," he said. "While this has not been proven, that's a possible mechanism...because in myocardial infarction oxygen is needed more to provide more energy, and having more oxygenated blood through higher hematocrit, that could provide a mechanism for that benefit."

"Since both hepcidin and ferritin are association with pro-inflammatory state and since both of them are mainly secreted and produced by the liver, it is possible that SGLT-2's have a major impact on the liver and it's another target for SGLT-2 action," Ghanim noted. "This could also lead us to think that it is possible that we could use SGLT-inhibitors in conditions of liver inflammation, like NASH and fatty liver disease."

"These are future ideas we could explore based on our data," he said.

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