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Empagliflozin increases plasma levels of citrulline, histidine, and α-aminobutyric acid in patients with type 2 diabetes: effects of a sodium-glucose co-transporter 2 inhibitor on the plasma amino acid profile

Jojima T, Sakurai S, Kishi H, Kato K, Iijima T, Tomaru T, Usui I, Aso Y

Expert opinion on pharmacotherapy, 2024

58 participants

Abstract

BACKGROUND: To investigate effects of empagliflozin on plasma amino acids in people with type 2 diabetes.

RESEARCH DESIGN AND METHODS: In a randomized, active-controlled, open-label trial, 58 patients with type 2 diabetes were randomized to 10 mg/day empagliflozin (n = 29) or standard treatment without empagliflozin (control group, n = 29) and treated for 12 weeks. We obtained blood samples at baseline and 12 weeks and assessed the plasma amino acid profile by liquid chromatography-mass spectrometry liquid chromatography. We also calculated the Fischer ratio (the ratio of branched-chain to aromatic amino acids).

RESULTS: In the empagliflozin group but not in the control group, plasma levels of citrulline, histidine, and α-aminobutyric acid (AABA), the Fischer ratio, and serum high-molecular weight (HMW) adiponectin increased significantly (p = 0.0099, 0.0277, 0.0318, 0.0135, and 0.0304, respectively) and plasma plasminogen activator inhibitor-1 (PAI-1) decreased significantly (p = 0.0014). In the empagliflozin group, the change in plasma citrulline was positively correlated with the changes in HMW adiponectin (r = 0.488, p = 0.0084) and the Fischer ratio (r = 0.393, p = 0.0353) but negatively correlated with the change in ferritin (r= -0.533,p = 0.0051); the change in plasma histidine was negatively correlated with the change in PAI-1 (r= -0.398, p = 0.0397) and urinary albumin creatinine ratio (r= -0.478, p = 0.0088).

CONCLUSION: Empagliflozin significantly increases plasma…

How strong is the evidence?

Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 58 participants or records.

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