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.

IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pharmacotherapy Pub Date : 2023-12-01 Epub Date: 2023-10-12 DOI:10.1002/phar.2884
Ayano Tsukagoshi-Yamaguchi, Masaya Koshizaka, Ryoichi Ishibashi, Ko Ishikawa, Takahiro Ishikawa, Mayumi Shoji, Shintaro Ide, Kana Ide, Yusuke Baba, Ryo Terayama, Akiko Hattori, Minoru Takemoto, Yasuo Ouchi, Yoshiro Maezawa, Koutaro Yokote
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Abstract

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.

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日本2型糖尿病患者异丙列嗪和二甲双胍治疗临床研究血清样本的代谢组学分析:探索与内脏脂肪减少相关的人类代谢产物。
目的:在之前的一项研究中,将钠依赖性葡萄糖转运蛋白2抑制剂异丙列嗪与二甲双胍的作用进行了比较,结果显示异丙列津可降低12%的内脏脂肪含量;然而,其根本机制尚不清楚。因此,该子分析旨在比较与异丙列嗪和二甲双胍相关的代谢组学变化,这些变化可能有助于其生物效应。材料和方法:在先前的研究中,103名2型糖尿病患者被随机分配接受ipragliflozin 50 mg或二甲双胍1000 mg每日治疗。在103名患者中,选择了内脏脂肪面积减少最多的15名ipragliflozin组患者和具有匹配特征的15名二甲双胍组患者,如年龄、性别、基线A1C、基线内脏脂肪面积、吸烟状态和伴随用药。对临床数据进行重新分析,并对之前和24小时收集的血清样本进行代谢组学分析 给药后数周使用毛细管电泳飞行时间质谱法进行。结果:24小时后平均内脏脂肪面积减少 ipragliflozin组(-19.8%)的治疗周数显著大于二甲双胍组(-2.5%)(P=0.002),皮下脂肪面积和体重也是如此。两组的A1C和血糖水平均下降。ipragliflozin组的谷丙转氨酶、γ-谷氨酰转移酶、尿酸和甘油三酯水平下降。二甲双胍组低密度脂蛋白胆固醇水平下降。ipragliflozin给药后,N2-苯乙酰谷氨酰胺、肌苷、鸟苷和1-甲基腺苷水平升高,而半乳糖胺、葡糖胺、11-氨基十一酸、吗啉和胆碱水平降低。二甲双胍给药后,二甲双胍、低牛磺酸、甲硫氨酸、甲基-2-氧代戊酸、3-硝基酪氨酸和环己胺水平升高,而瓜氨酸、辛酸、吲哚-3-乙醛和己酸水平降低。结论:在异丙列嗪组中检测到可能影响内脏脂肪减少的代谢产物。需要进行研究以进一步阐明潜在的机制。
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来源期刊
Pharmacotherapy
Pharmacotherapy 医学-药学
CiteScore
7.80
自引率
2.40%
发文量
93
审稿时长
4-8 weeks
期刊介绍: Pharmacotherapy is devoted to publication of original research articles on all aspects of human pharmacology and review articles on drugs and drug therapy. The Editors and Editorial Board invite original research reports on pharmacokinetic, bioavailability, and drug interaction studies, clinical trials, investigations of specific pharmacological properties of drugs, and related topics.
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