TOP LINE:
In patients with type 2 diabetes (T2D) and steatotic liver disease associated with metabolic dysfunction (MASLD), the risk of serious liver injury appears to be similar when taking dipeptidyl peptidase 4 (DPP-4) and sodium-glucose cotransporter 2 (SGLT2) inhibitors.
METHODOLOGY:
- Regarding potential side effects, the antidiabetic drugs SGLT2 inhibitors are believed to protect patients with type 2 diabetes and MASLD from the subsequent development of liver cirrhosis and hepatocellular carcinoma, the most common causes of death in MASLD. However, there is no study that has investigated the effects of SGLT2 on important liver damage.
- This retrospective cohort study used a US health insurance claims database to evaluate the comparative effectiveness of SGLT2 and DPP-4 inhibitors in reducing the risk of major liver injury in patients with type 2 diabetes and MASLD.
- The real-world study included 44,651 patients (mean age 53.2 years; 52.8% women; SGLT2 inhibitors: n = 22,100; DPP-4 inhibitors: n = 22,551) who were taking metformin and had no specific liver disease.
- The primary outcome measure was the incidence of combined major liver injuries, including cirrhosis and hepatocellular carcinoma.
- All patients were followed up until the onset of severe liver injury or until their withdrawal from the study, whichever occurred first (mean 3.2 years). A propensity score method was used to account for potential confounding factors.
TAKE AWAY:
- The incidence of serious liver injury did not differ significantly between the SGLT2 and DPP-4 inhibitor groups (adjusted hazard ratio (HR): 0.92; 95% CI: 0.6–1.1).
- Separate analyses of key liver outcomes showed no significant difference in the incidence of liver cirrhosis and hepatocellular carcinoma (adjusted HR 0.77 and 0.99, respectively; 95% CI 0.55–1.06 and 0.47–1.83, respectively).
- Initiation of treatment with an SGLT2 inhibitor was not associated with a lower incidence of combined major liver injury in any of the subgroups studied, including those who were already overweight at baseline and were using statins or insulin preparations.
- In addition, the type of SGLT2 inhibitor used (canagliflozin, dapagliflozin or empagliflozin) had no influence on the risk of serious liver injury.
IN PRACTICE:
“In the specific context of MASLD, it is advisable to have thorough discussions with patients, pharmacists and other healthcare professionals when choosing pharmacotherapy between an SGLT2i (SGLT2 inhibitor) or a DPP4i (DPP-4 inhibitor), taking into account both efficacy and safety,” the authors write, while urging caution in interpreting the results.
SOURCE:
The study was led by Tsung-Hua Shen, BPharm, College of Pharmacy, University of Minnesota, Minneapolis. It was published online in Diabetes, obesity and metabolism.
RESTRICTIONS:
The retrospective design of this study limited the ability to collect some information, such as data on laboratory measurements and progression of MASLD. The database did not include data on alcohol consumption, and the study could not account for alcohol abuse in the context of MASLD. The generalizability of the study was limited to privately insured individuals, who are typically younger than 65 years of age, which may underestimate the incidence of cirrhosis or hepatocellular carcinoma. The development of cirrhosis and hepatocellular carcinoma likely requires a longer time frame, so the study may not be powered to detect such outcomes. The study did not include glucagon-like peptide-1 receptor agonists, which could potentially provide liver protection.
DISCLOSURE:
No funding was provided for this study. One author reported receiving personal fees for consulting for a pharmaceutical company.
Several editorial tools, including AI, were used to create this article. Human editors reviewed the content before publication.
