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Pilot study in pharmacogenomic management of empagliflozin in type 2 diabetes mellitus patients

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Abstract

Background

Type 2 diabetes mellitus (T2DM) is a metabolic disorder in which the patients with high blood sugar develop insufficient insulin secretion or insulin resistance. The solute carrier family, 5 member 2 (SLC5A2) gene is a member of sodium/glucose transporter family which can reduce heart and kidney problems. The current study aims to look into any association between rs11646054 variant in SLC5A2 gene and the anti-diabetic efficacy and safety of empagliflozin.

Methods

14 T2DM who failed to respond to previous treatments, empagliflozin 10 mg was added for 6 months. Genotyping of the rs11646054 variant of SLC5A2 gene was performed by polymerase chain reaction (PCR) followed by Sanger sequencing.

Results

Although hemoglobin A1c (HbA1c) and low-density lipoprotein (LDL) were not significantly different, but the mean fasting blood sugar (FBS), 2-h post prandial (2hpp), albumin-to-creatinine ratio (ACR), and total cholesterol (TC) were significantly decreased after 6 months empagliflozin treatment. There was a significant difference in the mean final reductions in FBS level among genotypes. It's important to mention that those who were GG homozygotes had a tendency to have more decrements.

Conclusions

The study results indicate that effects of variation in SLC5A2 (rs11646054) on the clinical efficacy of empagliflozin were negligible.

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Abbreviations

T2DM:

Type 2 diabetes mellitus

DPP4i:

Dipeptidyl peptidase -4 inhibitors

GLP-1:

Glucagon-like peptide-1

SGLT2i:

Sodium glucose transporter -2 inhibitors

ADA:

American diabetes association

EASD:

European association for the study of diabetes

HbA1c:

Hemoglobin A1c

SLC5A2:

Solute carrier family 5 member 2

SNPs:

Single nucleotide polymorphisms

eGFR:

Estimated glomerular filtration rate

FBS:

Fasting blood sugar

2hpp:

2-Hour post prandial

TC:

Total cholesterol

LDL:

Low-density lipoprotein

DPN:

Diabetic polyneuropathy

UTI:

Urinary tract infections

BMI:

Body mass index

ACR:

Albumin-to-creatinine ratio

AKI:

Acute kidney injury

DKA:

Diabetic ketoacidosis

HPLC:

High performance liquid chromatography

PCR:

Polymerase chain reaction

SD:

Standard deviation

HWE:

Hardy–Weinberg equilibrium

OR:

Odds ratios

CI:

Confidence intervals

SBP:

Systolic blood pressure

OGTT:

Oral glucose tolerance test

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Acknowledgements

The authors thank to T2DM patients who participated in this study.

Funding

No funding was obtained.

Author information

Authors and Affiliations

  1. Personalized Medicine Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Mahdieh Jamalizadeh, Mandana Hasanzad & Negar Sarhangi

  2. Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Mahdieh Jamalizadeh & Ensieh Nasli-Esfahani

  3. Medical Genomics Research Center, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Mandana Hasanzad

  4. Elderly Health Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Farshad Sharifi

  5. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, No.10-Jalal-e-Ale-Ahmad Street, Chamran Highway, 1411713119, Tehran, Iran

    Bagher Larijani

Authors
  1. Mahdieh Jamalizadeh
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  2. Mandana Hasanzad
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  3. Negar Sarhangi
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  4. Farshad Sharifi
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  5. Ensieh Nasli-Esfahani
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  6. Bagher Larijani
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Contributions

MJ and NS drafted the manuscript and performed lab genotyping; MH provided genetic guidance to the research; FSH performed the statistical analysis; ENE: provided clinical guidance to the research; and BL managed the project. All authors contributed to and approved the final version of the manuscript.

Corresponding author

Correspondence to Bagher Larijani.

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Competing of interest

There are no conflicts of interest declared by the authors.

Consent for publication

The present study research is approved by endocrinology and metabolism clinical institute ethics committee (IR.TUMS.MEDICINE.REC.1399.716) and all T2DM patients signed written consent forms.

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Jamalizadeh, M., Hasanzad, M., Sarhangi, N. et al. Pilot study in pharmacogenomic management of empagliflozin in type 2 diabetes mellitus patients. J Diabetes Metab Disord 20, 1407–1413 (2021). https://doi.org/10.1007/s40200-021-00874-4

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  • DOI: https://doi.org/10.1007/s40200-021-00874-4

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