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  2. Therapy of empagliflozin plus metformin on T2DM mice shows no higher amelioration for glucose and lipid metabolism than empagliflozin monotherapy

Therapy of empagliflozin plus metformin on T2DM mice shows no higher amelioration for glucose and lipid metabolism than empagliflozin monotherapy

  • Life Sci. 2019 Sep 1;232:116622. doi: 10.1016/j.lfs.2019.116622.
Zhiguo Wang 1 Ji Zhou 2 Mengran Lu 2 Yuwan Liang 2 Zhengxuan Jiang 3 Keyang Chen 4
Affiliations

Affiliations

  • 1 Department of Public Health Inspection and Quarantine, Anhui Medical University School of Public Health, Hefei, Anhui 230032, China; Department of Clinical Laboratory, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
  • 2 Department of Public Health Inspection and Quarantine, Anhui Medical University School of Public Health, Hefei, Anhui 230032, China.
  • 3 Department of Ophthalmology, Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China. Electronic address: jiangzhengxuan@ahmu.edu.cn.
  • 4 Department of Public Health Inspection and Quarantine, Anhui Medical University School of Public Health, Hefei, Anhui 230032, China; Department of Ophthalmology, Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China. Electronic address: chenkeyang@ahmu.edu.cn.
Abstract

Aims: This study was designed to compare the effects of empagliflozin monotherapy and its combination with metformin on glucose and lipid modulations in T2DM mice.

Main methods: Nine-week-old male C57BLKS/J db/db mice (n = 32) were used as T2DM model, and their age-matched C57BLKS/J db/m mice (n = 8) were used as normal control. A total of 32 db/db mice were randomly divided into four groups (n = 8/group): the DMT1 group, treated with metformin (250 mg/kg/day); the DMT2 group, treated with metformin (250 mg/kg/day) plus empagliflozin (10 mg/kg/day); the DMT3 group, treated with empagliflozin (10 mg/kg/day); the T2DM control group (DM), received 0.5% Natrosol. The db/m mice received same administration as DM group.

Key findings: After four-week treatments, compared with T2DM control (DM), the empagliflozin or its combination with metformin dramatically increased the levels of plasma HDL-C (139.6% and 154.9%, respectively), with significant decrease in plasma TC (22.9% and 13.7%, respectively) and plasma TG (26% and 19.7%, respectively) and in hepatic TG (30.3% and 28.6%, respectively). The protein expressions of SREBP1c (75.3% and 54.0%, respectively) and APOC-III (51.2% and 50.2%, respectively) were reduced, while CPT1A (304.0% and 221.4%, respectively) and ApoA1 levels (90.0% and 85.3%, respectively) were enhanced. Although both interventions improve above-mentioned lipid homeostasis, there were no statistic differences between two groups (p > 0.05).

Significance: Our study demonstrated that current dose of combination therapy may have no higher amelioration than empagliflozin monotherapy for glucose and lipid metabolism in male T2DM mice when it followed a treatment shorter than that expected during clinical treatment.

Keywords

Combined therapy; Empagliflozin; Lipid and glucose metabolism; T2DM mice.

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