Metabolomic analysis of serum samples from a clinical study on ipragliflozin and metformin treatment in Japanese patients with type 2 diabetes: Exploring human metabolites associated with visceral fat reduction.

Autor: Tsukagoshi-Yamaguchi A; Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba City, Japan., Koshizaka M; Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba City, Japan.; Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba City, Japan.; Center for Preventive Medical Science, Chiba University, Chiba City, Japan., Ishibashi R; Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba City, Japan.; Division of Diabetes, Endocrinology, and Metabolism, Kimitsu Chuo Hospital, Kisarazu City, Japan., Ishikawa K; Department of Diabetes and Endocrinology, Chiba Rosai Hospital, Ichihara City, Japan., Ishikawa T; Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba City, Japan.; Department of General Medical Science, Chiba University Graduate School of Medicine, Chiba City, Japan., Shoji M; Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba City, Japan.; Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba City, Japan., Ide S; Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba City, Japan.; Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba City, Japan., Ide K; Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba City, Japan.; Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba City, Japan., Baba Y; Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba City, Japan.; Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba City, Japan., Terayama R; Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba City, Japan., Hattori A; Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba City, Japan.; Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba City, Japan., Takemoto M; Division of Diabetes, Department of Medicine, Metabolism and Endocrinology, International University of Health and Welfare, Narita City, Japan., Ouchi Y; Department of Regenerative Medicine, Chiba University Graduate School of Medicine, Chiba City, Japan.; Altos Labs, California, San Diego, USA., Maezawa Y; Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba City, Japan.; Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba City, Japan., Yokote K; Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba City, Japan.; Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba City, Japan.
Jazyk: angličtina
Zdroj: Pharmacotherapy [Pharmacotherapy] 2023 Dec; Vol. 43 (12), pp. 1317-1326. Date of Electronic Publication: 2023 Oct 12.
DOI: 10.1002/phar.2884
Abstrakt: Study Objective: The effects of the sodium-dependent glucose transporter-2 inhibitor ipragliflozin were compared with metformin in a previous study, which revealed that ipragliflozin reduced visceral fat content by 12%; however, the underlying mechanism was unclear. Therefore, this sub-analysis aimed to compare metabolomic changes associated with ipragliflozin and metformin that may contribute to their biological effects.
Design: A sub-analysis of a randomized controlled study.
Setting: Chiba University Hospital and ten hospitals in Japan.
Patients: Fifteen patients with type 2 diabetes in the ipragliflozin group and 15 patients with type 2 diabetes in the metformin group with matching characteristics, such as age, sex, baseline A1C, baseline visceral fat area, smoking status, and concomitant medication.
Interventions: Ipragliflozin 50 mg or metformin 1000 mg daily.
Measurements: The clinical data were reanalyzed, and metabolomic analysis of serum samples collected before and 24 weeks after drug administration was performed using capillary electrophoresis time-of-flight mass spectrometry.
Main Results: The reduction in the mean visceral fat area after 24 weeks of treatment was significantly larger (p = 0.002) in the ipragliflozin group (-19.8%) than in the metformin group (-2.5%), as were the subcutaneous fat area and body weight. The A1C and blood glucose levels decreased in both groups. Glutamic pyruvic oxaloacetic transaminase, γ-glutamyl transferase, uric acid, and triglyceride levels decreased in the ipragliflozin group. Low-density lipoprotein cholesterol levels decreased in the metformin group. After ipragliflozin administration, N2-phenylacetylglutamine, inosine, guanosine, and 1-methyladenosine levels increased, whereas galactosamine, glucosamine, 11-aminoundecanoic acid, morpholine, and choline levels decreased. After metformin administration, metformin, hypotaurine, methionine, methyl-2-oxovaleric acid, 3-nitrotyrosine, and cyclohexylamine levels increased, whereas citrulline, octanoic acid, indole-3-acetaldehyde, and hexanoic acid levels decreased.
Conclusions: Metabolites that may affect visceral fat reduction were detected in the ipragliflozin group. Studies are required to further elucidate the underlying mechanisms.
(© 2023 Pharmacotherapy Publications, Inc.)
Databáze: MEDLINE
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