SGLT2 inhibitors improve outcomes over DPP4 inhibitors in type 2 diabetes with liver cirrhosis

medwireNews: Sodium–glucose cotransporter (SGLT)2 inhibitors are associated with a significantly lower risk for adverse kidney, cardiovascular, and hepatic outcomes compared with dipeptidyl peptidase (DPP)-4 inhibitors in patients with both type 2 diabetes and liver cirrhosis, reveals a Taiwanese analysis.

“Importantly, these protective associations were consistent across the full spectrum of cirrhosis causes, including viral hepatitis, alcoholic liver disease, and nonalcoholic steatohepatitis, and remained robust after multivariable adjustment,” say Chi-Jung Chung (China Medical University, Taichung City, Taiwan) and colleagues in JAMA Network Open.

They add: “By interrupting key metabolic and hemodynamic pathways underlying [type 2 diabetes] and liver disease, SGLT2 [inhibitors] may offer meaningful clinical benefits for this high-risk population. Prospective studies are warranted to confirm these findings.”

There is a bidirectional relationship between type 2 diabetes and cirrhosis, the researchers say, in that approximately 31% of cirrhosis patients have type 2 diabetes, and diabetes patients are around twice as likely as the general population to develop cirrhosis. The combination results in “substantially worse outcomes” than either alone, they explain.

As patients with advanced liver disease have largely been excluded from randomized clinical trials in diabetes, the team examined Taiwan’s National Health Insurance Research Database for adults with both type 2 diabetes and liver cirrhosis. They identified 38,743 suitable patients who initiated SGLT2 inhibitors or DPP4 inhibitors between May 2016, when SGLT2 inhibitors were first approved in Taiwan, and December 2023.

After excluding individuals with prior cancer or end-stage kidney disease (ESKD) or chronic (C)KD stage IV or V before the index date, as well as those who had taken SGLT2 inhibitors or DPP4 inhibitors within the previous 12 months, 24,259 patients were included. They had a mean age of 64.7 years, 66.1% were men, and the majority (60.1%) received DPP4 inhibitors, while the remainder (39.9%) received SGLT2 inhibitors.

Overall, SGLT2 inhibitor users were younger, more likely to be male, and more likely to have hyperlipidemia than those given DPP4 inhibitors, but were less likely to have cerebrovascular disease, hepatitis C infection, stroke, and hypoglycemia. SGLT2 inhibitor users were also more likely to use insulin and statins and had a longer diabetes duration. Inverse probability of treatment weighting was therefore used to balance the two treatment groups with regard to baseline comorbidity and medication use.

Over a median follow-up of 2.3 years, SGLT2 inhibitor users had a significantly reduced risk for ESKD compared with patients treated with DPP4 inhibitors (2.3 vs 7.2 events per 1000 person–years) with an adjusted hazard ratio (aHR) of 0.34 after taking into account diabetes duration, age, sex, comorbidities, and concomitant medications.

Compared with DPP4 inhibitor use, SGLT2 inhibitor use was also associated with a significantly reduced risk for acute kidney injury (22.2 vs 37.7 per 1000 person–years, aHR=0.66), and major adverse cardiovascular events (MACE; 65.4 vs 114.7 per 1000 person–years, aHR=0.67).

Among the MACE components, SGLT2 inhibitor use was linked to a significantly lower risk for acute myocardial infarction (aHR=0.60), stroke (aHR=0.72), and all-cause mortality (aHR=0.58), but not with heart failure.

Treatment with SGLT2 inhibitors was associated with a significantly lower incidence of hepatic decompensation compared with DPP4 inhibitor use both overall (aHR=0.65), and among subgroups of patients based on kidney comorbidity, hepatitis viral infection status, alcohol-related cirrhosis, or nonalcoholic steatohepatitis [metabolic dysfunction-associated steatohepatitis] status, and use of oral and direct-acting antivirals and mineralocorticoid receptor agonists.

This was also true for the specific hepatic decompensation events of ascites (aHR=0.65), peritonitis (aHR=0.62), and esophageal variceal bleeding (aHR=0.67).

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JAMA Netw Open 2026; 9; e2560429