Dear Editor,
We read with great interest the target trial emulation study by Mao et al. [
1], which assessed the association between glucagon-like peptide-1 receptor agonists (GLP- 1RAs) and liver and non-liver outcomes in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD) [
1]. The authors reported that GLP-1RA use was associated with significantly lower risks of hepatocellular carcinoma (HCC), cirrhosis, cardiovascular disease, chronic kidney disease, and non-liver cancer compared with dipeptidyl peptidase-4 inhibitors. However, we would like to raise a methodological concern that may impact the interpretation of the findings.
We noted that the Kaplan–Meier curves for both HCC and non-liver cancer diverged early within the first month of follow-up (Fig. 2). Given the long latency periods and heterogeneous progression patterns of most cancers, such an immediate separation in incidence curves raises concerns regarding potential residual confounding or selection bias. We suggest that a sensitivity analysis excluding cancer outcomes diagnosed within the first year (or even the first two years) of follow-up could help clarify whether the observed associations reflect true long-term protective effects of GLP-1RAs rather than early detection or baseline imbalances.
In conclusion, Mao et al.’s study [
1] adds valuable insight into the potential benefits of GLP-1RAs in patients with MASLD and T2D. However, we caution that the early divergence of cancer-related outcomes may reflect residual confounding. Additional sensitivity analyses would strengthen confidence in the causal interpretation of these findings and guide clinical decision-making.
FOOTNOTES
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Authors’ contributions
SSJ, write the draft. CCL, review and revision.
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Conflicts of Interest
The authors have no conflicts to disclose.
Abbreviations
glucagon-like peptide-1 receptor agonists
metabolic dysfunction-associated steatotic liver disease
REFERENCES
- 1. Mao X, Zhang X, Lai R, Cheung KS, Yuen MF, Cheung R, et al. Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study. Clin Mol Hepatol 2025;31:1084-1099.
Citations
Citations to this article as recorded by
- Correspondence to letter to the editor 1 on “Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study
Xianhua Mao, Mindie H. Nguyen
Clinical and Molecular Hepatology.2026; 32(2): e231. CrossRef
