SGLT2 Inhibitors Lower NAFLD, HCC Risks Over DPP4i

Miriam E. Tucker, for Medscape

September 01, 2022

The study covered in this summary was published in medRxiv as a preprint and has not yet been peer reviewed.

Key Takeaways

  • Sodium glucose cotransporter 2 inhibitors (SGLT2is) lowered the risk of nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) in comparison with dipeptidyl peptidase-4 inhibitors (DPP4is) after propensity score matching and adjustments.

  • SGLT2is were also associated with lower risk of cancer-related mortality and all-cause mortality compared to DPP4is.

Why This Matters

  • The risk of developing HCC and of HCC-related mortality increases in people with type 2 diabetes (T2D).

  • Metformin has been shown to protect against HCC, and there is interest in exploring the potential protective effects of newer glucose-lowering medications.

Study Design

  • The retrospective population-based cohort study, which included 62699 patients with T2D treated with either SGLT2i (n = 22,154) or DPP4i (n = 40,545), was conducted in Hong Kong from 2015 to 2019. The cohorts were comparable after matching.

Key Results

  • Follow-up was through 2020; total follow-up included 236856.5 person-years. The incidence rate (IR) of NAFLD was lower among SGLT2i users (IR, 3.4; 95% CI, 3.0 – 3.7) than among DPP4i users (IR, 5.9; 95% CI, 5.5 – 6.4) after propensity score matching.

  • After 239941.9 person-years of follow-up, the incidence of HCC was lower among SGLT2I users (IR, 0.3; 95% CI, 0.2 – 0.4) than among DPP4i users (IR,1.3; 95% CI,1.1 – 1.5).

  • Among SGLT2i users, the risk of cancer-related mortality was lower (IR, 1.1; 95% CI, 0.9 – 1.3) than among DPP4i users (IR, 6.6; 95% CI, 6.1 – 7.1), as was the risk of all-cause mortality (IR, 5.0; 95% CI, 4.6 – 5.4) in comparison with DPP4i users (IR, 24.4; 95% CI, 23.6 – 25.4).

  • In multivariable models, the risk of NAFLD was lower among SGLT2i (hazard ratio [HR], 0.39; 95% CI, 0.34 – 0.46), HCC (HR, 0.46; 95% CI, 0.29 – 0.72), cancer-related mortality (HR, 0.29; 95% CI, 0.23 – 0.37) and all-cause mortality (HR, 0.28; 95% CI, 0.25 – 0.31) after adjustments.


  • The study was observational, and there was a potential for coding errors and missing data.

  • The study was retrospective and cannot prove causation.

  • Medication adherence could not be directly assessed.

  • The investigators had no information on NAFLD and HCC behavioral risk factors.

  • Drug exposure duration was not controlled.


  • The study was funded by the National Cancer Institute.

  • The authors have disclosed no relevant financial relationships.

This is a summary of a preprint research study, "Lower Risks of Sodium Glucose Cotransporter 2 (SGLT2) Inhibitors Compared to Dipeptidyl Peptidase-4 (DPP4) Inhibitors for New-Onset Non-alcoholic Fatty Liver Disease and Hepatocellular Carcinoma in Type 2 Diabetes Mellitus: A Population-Based Study," by Oscar Hou In Chou, of the School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China and the Diabetes Research Unit, Cardiovascular Analytics Group, Hong Kong, and colleagues. It is provided to you by Medscape. The study has not yet been peer reviewed.

For more news, follow Medscape on Facebook, Twitter, Instagram, and YouTube.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.