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TOPLINE:

In patients with type 2 diabetes (T2D) and metabolic dysfunction–associated steatotic liver disease (MASLD), the risk for major liver outcomes appears similar with dipeptidyl peptidase 4 (DPP-4) and sodium-glucose cotransporter 2 (SGLT2) inhibitors.

METHODOLOGY:

• In potential secondary effects, the antidiabetic drugs SGLT2 inhibitors are hypothesized to protect patients with T2D and MASLD from subsequent development of cirrhosis and hepatocellular carcinoma, top causes of death in MASLD, but no study has investigated SGLT2 effects on major liver outcomes.
• 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 for major liver outcomes in patients with T2D 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 using metformin and did not have any specific liver condition.
• The primary endpoint was the incidence of composite major liver outcomes, encompassing cirrhosis and hepatocellular carcinoma.
• All patients were followed up (median, 3.2 years) until the occurrence of major liver outcomes or until they were censored from the study, whichever came first, and a propensity score method was used to address potential confounding factors.

TAKEAWAY:

• The incidence rate of any major liver outcomes was not significantly different between the SGLT2 vs DPP-4 inhibitor groups (adjusted hazard ratio [HR], 0.92; 95% CI, 0.6-1.1).
• Separate analyses of major liver outcomes showed no significant difference in the incidence of cirrhosis and hepatocellular carcinoma (adjusted HR, 0.77 and 0.99; 95% CI, 0.55-1.06 and 0.47-1.83, respectively).
• Initiation of an SGLT2 inhibitor was not associated with lower incidence rates of composite major liver outcomes for all subgroups studied, including those with baseline obesity, statin use, or insulin use.
• Moreover, the type of SGLT2 inhibitor used (canagliflozin, dapagliflozin, or empagliflozin) did not have an impact on the risk for major liver outcomes.

IN PRACTICE:

"In the specific context of MASLD, it is advisable to engage in thorough discussions with patients, pharmacists and other healthcare professionals regarding the choice of pharmacotherapy, considering both effectiveness and safety, when deciding between an SGLT2i [SGLT2 inhibitor] or a DPP4i [DPP-4 inhibitor]," wrote the authors, who also urged 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.

LIMITATIONS:

The retrospective design of this study limited its ability to collect some information, such as data on laboratory measurements and MASLD progression. The database did not contain data regarding alcohol intake, and the study was unable to consider alcohol abuse in the context of MASLD. The study's generalizability was limited to commercially insured individuals, who are usually younger than 65 years, potentially underestimating the incidence of cirrhosis or hepatocellular carcinoma. The development of cirrhosis and hepatocellular carcinoma probably requires a longer timeframe, so the study may be underpowered to detect such outcomes. The study did not include glucagon-like peptide 1 receptor agonists, which could potentially confer liver protection.

DISCLOSURES:

This study did not receive any funding. One author disclosed receiving personal fees for consulting work provided to a pharmaceutical company.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.