Effect of Empagliflozin on the Metabolic Signature of Patients With Type 2 Diabetes Mellitus and Cardiovascular Disease
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- branched-chain amino acids
- cardiovascular disease
- ketone bodies
- SGTL2 inhibitors
- type 2 diabetes mellitus
In the recent EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), treatment with empagliflozin, a member of the group of antidiabetic sodium-glucose cotransporter 2 inhibitors, reduced cardiovascular mortality and hospitalization for heart failure in patients with type 2 diabetes mellitus and cardiovascular disease.1 In heart failure and type 2 diabetes mellitus, cardiac metabolic flexibility is impaired, and alteration in glucose or fatty acid (FA) metabolism and changes in the use of ketone bodies and branched chain amino acids (BCAAs) occur.2 Because sodium-glucose cotransporter 2 inhibitors lead to a mild increase in ketones, it has been hypothesized that empagliflozin may exhibit some of its beneficial effects through a shift in myocardial metabolism toward an energy-efficient use of ketone bodies, which may improve myocardial work efficiency and function.3,4 Still, these hypotheses are not proven yet, and data are lacking on the metabolic signature of sodium-glucose cotransporter 2 inhibitor-treated patients. Therefore, we performed an untargeted metabolomics approach in a group of empagliflozin-treated patients with type 2 diabetes mellitus and cardiovascular disease.
In a prospective study (http://www.clinicaltrials.org; unique identifier: NCT03131232; ethics committee approved, and all patients gave informed consent), we enrolled 25 patients with type 2 diabetes mellitus and cardiovascular disease with a clinical indication for intensification of their glucose-lowering therapy and treated them with empagliflozin 10 mg/day. Serum was taken at baseline and after 1 month.