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Empagliflozin for the Treatment of Nonalcoholic Steatohepatitis in Patients with Type 2 Diabetes Mellitus

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Abstract

Background and Aims

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of drugs that lower glucose by inducing renal glycosuria. We aimed to explore whether SGLT2 inhibitor added to the usual care for patients with type 2 diabetes mellitus (T2DM) and biopsy-proven nonalcoholic steatohepatitis (NASH) will benefit NASH histology.

Methods

In this investigator-initiated, single-arm, open-label, pilot study, nine biopsy-proven NASH patients with T2DM were given empagliflozin 25 mg daily for 24 weeks. Liver biopsy was repeated at the end of treatment. The histological outcomes were compared with the placebo group of a previous 48-week clinical trial.

Results

There was a significant reduction in body mass index (median change, Δ = −0.7 kg per m2, p = 0.011), waist circumference (Δ = −3 cm, p = 0.033), systolic blood pressure (Δ = −9 mmHg, p = 0.024), diastolic blood pressure (Δ = −6 mmHg, p = 0.033), fasting blood glucose (Δ = −1.7 mmol/L, p = 0.008), total cholesterol (Δ = −0.5 mmol/L, p = 0.011), gamma glutamyl transpeptidase (Δ = −19 U/L, p = 0.013), volumetric liver fat fraction (Δ = −7.8%, p = 0.017), steatosis (Δ = −1, p = 0.014), ballooning (Δ = −1, p = 0.034), and fibrosis (Δ = 0, p = 0.046). All histological components either remained unchanged or improved, except in one patient who had worsening ballooning. Empagliflozin resulted in significantly greater improvements in steatosis (67% vs. 26%, p = 0.025), ballooning (78% vs. 34%, p = 0.024), and fibrosis (44% vs. 6%, p = 0.008) compared with historical placebo.

Conclusion

This pilot study provides primary histological evidence that empagliflozin may be useful for the treatment of NASH. This preliminary finding should prompt larger clinical trials to assess the effectiveness of empagliflozin and other SGLT2 inhibitors for the treatment of NASH in T2DM patients.

Trial registry number ClincialTrials.gov number, NCT02964715.

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Acknowledgment

The authors would like to thank Wan Nur Illyana Wan Yusoff, Wan Noor Hidayu, Talvant Kaur, and Soudamany Nair, for their assistance in the research project.

Funding

This study was funded by the University of Malaya Special Research Fund (Project No.: BK006-2016 and BKS067-2017). University of Malaya was not involved in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

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Author notes

  1. Lee-Lee Lai and Shireene Ratna Vethakkan are co-first authors for this work.

Authors and Affiliations

  1. Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Lee-Lee Lai, Sanjiv Mahadeva & Wah-Kheong Chan

  2. Endocrine Unit, Department of Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Shireene Ratna Vethakkan

  3. Department of Pathology, Hospital Sultanah Bahiyah, Alor Setar, Kedah, Malaysia

    Nik Raihan Nik Mustapha

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  1. Lee-Lee Lai
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  2. Shireene Ratna Vethakkan
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  4. Sanjiv Mahadeva
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  5. Wah-Kheong Chan
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Corresponding authors

Correspondence to Shireene Ratna Vethakkan or Wah-Kheong Chan.

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Supplementary Figure 1

The histological outcomes of patients who received empagliflozin 25 mg daily for 24 weeks compared with patients with type 2 diabetes mellitus from the placebo group of a 48-week clinical trial previously conducted at the same center (TIFF 1374 kb)

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Lai, LL., Vethakkan, S.R., Nik Mustapha, N.R. et al. Empagliflozin for the Treatment of Nonalcoholic Steatohepatitis in Patients with Type 2 Diabetes Mellitus. Dig Dis Sci 65, 623–631 (2020). https://doi.org/10.1007/s10620-019-5477-1

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