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Empagliflozin combined with short-term intensive insulin therapy improves glycemic variability and 1,5-anhydroglucitol in patients with type 2 diabetes: a randomized clinical trial

  • Original Article
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International Journal of Diabetes in Developing Countries Aims and scope Submit manuscript

Abstract

Objective

We aimed to compare glycemic variability (GV) parameters using both a flash glucose monitoring (FGM) system and cardiometabolic risk parameters in hospitalized patients with type 2 diabetes mellitus (T2DM) between cohorts receiving short-term intensive insulin infusion (STII) plus empagliflozin (EMPA) combination therapy vs. STII therapy alone.

Methods

In a 2-week, open-label, randomized, parallel-group clinical trial, newly diagnosed patients with T2DM [fasting plasma glucose (FPG) > 11.1 mmol/L or hemoglobin A1c (HbA1c) > 9.0%] or patients with poor glycemic control (HbA1c > 7.0%) on oral antidiabetic drugs (OAD) received either STII+EMPA therapy (n = 30) or STII therapy alone (n = 30). FGM was carried over 14 days, and the data were used to calculate time in range (TIR [3.9–10 mmol/L]) and compare GV parameters. 1,5-Anhydroglucitol (1,5-AG) and cardiometabolic indicators of oxidative stress, inflammation, and vascular endothelial function were also compared.

Results

After treatment, the TIR percentage was significantly higher (p < 0.05), and the time below range (TBR; < 3.9 mmol/L) was significantly lower (p < 0.05) in the STII+EMPA group than that in the STII group. The various measured glycemic parameters were significantly lower, and the average daily dose of insulin was also significantly lower in patients with STII+EMPA treatment (all p < 0.05). Plasma 1,5-AG levels were significantly higher (p < 0.05) in the STII+EMPA group than that in the control group.

Conclusions

Newly diagnosed patients with T2DM or with poor glycemic control on OAD attained greater benefit and lower GV from STII+EMPA treatment than that for STII treatment alone. The 1,5-AG marker is a good indicator of the effects of short-term glycemic control.

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Data availability

The original contributions presented in the study are included in the article material; further inquiries can be directed to the corresponding author upon reasonable request.

Abbreviations

GV:

Glycemic variability

FGM:

Flash glucose monitoring

T2DM:

Type 2 diabetes mellitus

STII:

Short-term intensive insulin infusion

EMPA:

Empagliflozin

FPG:

Fasting plasma glucose

HbA1c :

Hemoglobin A1c

OAD:

Oral antidiabetic drugs

TIR:

Time in range

1,5-AG:

1,5-Anhydroglucitol

TBR:

Time below range

SGLT2:

Sodium-glucose cotransporter 2 inhibitor

BMI:

Body mass index

MBG:

Mean blood glucose

LAGE:

Largest amplitude of glycemic excursions

SDBG:

Standard deviation of blood glucose

MAGE:

Mean amplitude of glucose excursions

CV:

Coefficient of variation

MODD:

Mean daily differences

GA:

Glycated albumin

TC:

Total cholesterol

TG:

Triglycerides

HDL-C:

High-density plasma glucose

LDL-C:

Low-density lipoprotein cholesterol

Hs-CRP:

Hypersensitive C-reactive protein

MDA:

Malondialdehyde

TNF-α:

Tumor necrosis factor-α

IL-6:

Interleukin-6

8-OHdG:

8-Hydroxydeoxyguanosine

8-iso-PGF2α:

8-Isoprostaglandin F2α

vWF:

von Willebrand Factor

VEGF:

Vascular endothelial growth factor

ELISA:

Enzyme-linked immunosorbent assay

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Acknowledgment

We thank all the participants of this study and the medical care professionals for their valuable contributions. We would like to thank Editage (www.editage.cn) for English language editing.

Funding

This work was supported by Hebei Health Commission, grant number: 20200924.

Author information

Authors and Affiliations

  1. Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China

    Zhihua Hao, Yuliang Zhao, Qiuxiao Zhu, Yanhong Ge, Zibo Liu, Yanxia Chen, Lijing Jiao, Xin Zhao, Xing Wang, Jing Wang, Jing Zhou, Huiyao Hao, Yongmei Hao, Hong Zhou, Mian Wang & Lihui Zhang

  2. Office of Academic Research, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China

    Zhihua Hao & Yuliang Zhao

Authors
  1. Zhihua Hao
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Contributions

ZH: research design, statistical analyses and interpretation of the data, drafting, and revision of the manuscript; LZ, YZ, YH, HZ, and MW: research design, statistics guidance, and revision of the manuscript; QZ, YG, and ZL: research design and conduction, collection of the data, and assistance in data analysis; YC, LJ, XZ, XW, JW, JZ, and HH: research conduction and collection of the data. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Lihui Zhang.

Ethics declarations

Ethics approval and consent to participate

The protocol was approved by the ethics committee of The Second Hospital of Hebei Medical University (No.2019-R078). Informed consent was obtained from all individual participants included in the study.

Trial registration

ChiCTR1900022412

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The authors declare no competing interests.

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Hao, Z., Zhao, Y., Zhu, Q. et al. Empagliflozin combined with short-term intensive insulin therapy improves glycemic variability and 1,5-anhydroglucitol in patients with type 2 diabetes: a randomized clinical trial. Int J Diabetes Dev Ctries (2023). https://doi.org/10.1007/s13410-023-01271-8

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