You are here

  • Home
  • Online First
  • Synergistic association of sodium-glucose cotransporter-2 inhibitor and metformin on liver and non-liver complications in patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease

Article Text

Article menu
Download PDFPDF
Hepatology
Original research
Synergistic association of sodium-glucose cotransporter-2 inhibitor and metformin on liver and non-liver complications in patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease
  1. Xianhua Mao1,2,
  2. Xinrong Zhang1,
  3. Leslie Kam1,
  4. Nicholas Chien1,
  5. Rongtao Lai1,3,
  6. Ka-Shing Cheung2,4,
  7. Man-Fung Yuen2,5,
  8. Ramsey Cheung1,6,
  9. Wai-Kay Seto2,4,5,
  10. Mindie H Nguyen1,7,8
  1. 1Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
  2. 2Department of Medicine, The University of Hong Kong, Hong Kong, China
  3. 3Department of Infectious Diseases, Shanghai Jiaotong University School of Medicine, Shanghai, China
  4. 4Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
  5. 5State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China
  6. 6Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA
  7. 7Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, California, USA
  8. 8Stanford Cancer Institute, Stanford University Medical Center, Palo Alto, California, USA
  1. Correspondence to Dr Mindie H Nguyen; mindiehn{at}stanford.edu

Abstract

Objective Type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease (diabetic MASLD) frequently coexist and worsen liver and non-liver outcomes, but effective pharmacological therapies are limited. We aimed to evaluate the long-term effect of sodium-glucose cotransporter-2 inhibitor (SGLT-2i) on liver and non-liver outcomes among patients with diabetic MASLD.

Design This population-based cohort study retrieved patients with diabetic MASLD from Merative Marketscan Research Databases (April 2013 and December 2021). The active comparator was other glucose-lowering drugs (oGLDs). Primary outcomes were liver complications including hepatocellular carcinoma (HCC) and liver cirrhosis, as well as non-liver complications including cardiovascular disease (CVD), chronic kidney disease (CKD) and non-liver cancer. Propensity score matching was applied and Cox regression models were conducted.

Results Compared with oGLD, SGLT-2i users had significantly lower risk of HCC (HR 0.76, 95% CI 0.62 to 0.93), liver cirrhosis (HR 0.80, 95% CI 0.76 to 0.84), CVD (HR 0.82, 95% CI 0.79 to 0.85) and CKD (HR 0.66, 95% CI 0.62 to 0.70), non-liver cancer (HR 0.81, 95% CI 0.76 to 0.86). Compared with patients without metformin and SGLT-2i, a stepwise decreasing risk was observed in users of either metformin or SGLT-2i (HRs 0.76–0.97) and in users of both medications (HRs 0.58–0.79). The lower risk also was shown in liver decompensation, compensated cirrhosis, major CVD, end-stage renal disease and specific common cancers (HRs 0.61–0.84).

Conclusion In a nationwide cohort, SGLT-2i users were associated with a substantially lower risk of liver and non-liver complications than oGLD users among patients with diabetic MASLD. The risk was further reduced with concomitant metformin use.

  • FATTY LIVER

Data availability statement

Data may be obtained from a third party and are not publicly available.

https://doi.org/10.1136/gutjnl-2024-332481

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Data availability statement

    Data may be obtained from a third party and are not publicly available.

    View Full Text

    Footnotes

    • Contributors Study concept and design: XM and MHN. Data acquisition: XM, XZ, LK and MHN. Data analysis: XM and MHN. Manuscript draft: XM and MHN. Data interpretation, critical review and revision of manuscript: all authors. Overall study supervision: MHN. All authors participated in the preparation of the manuscript and have seen and approved the final version. MHN is guarantor of the manuscript.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Disclaimer The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

    • Competing interests MHN received research grants via Stanford University from Pfizer, Enanta, Astra Zeneca, GSK, Delfi, Innogen, Exact Science, CurveBio, Gilead, Vir Biotech, Helio Health, National Cancer Institute, Glycotest and personal fees from consulting/advisory board from Intercept, Exact Science, Gilead, GSK. MFY received research funding from Assembly Biosciences, Arrowhead Pharmaceuticals, Bristol Myer Squibb, Fujirebio Incorporation, Gilead Sciences, Merck Sharp and Dohme, Springbank Pharmaceuticals, Sysmex Corporation, Roche and is an advisory board member and/or received research funding from AbbVie, Aligos therarpeutics, Arbutus Biopharma, Bristol Myer Squibb, Dicerna Pharmaceuticals, Finch Therapeutics, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, Clear B Therapeutics, Springbank Pharmaceuticals, Roche. W-KS received speaker’s fees and is an advisory board member of Abbott, received research funding from Alexion Pharmaceuticals, Boehringer Ingelheim, Pfizer and Ribo Life Science, received speaker’s fees and received research funding from AstraZeneca, and is an advisory board member, received speaker’s fees and researching funding from Gilead Sciences. The other authors have nothing to disclose.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.