SGLT2s Linked to Lower Cardiorenal, Hepatic Risks in Type 2 Diabetes

Patients living with both type 2 diabetes (T2D) and liver cirrhosis face a heightened risk of kidney failure, cardiovascular complications, and hepatic decompensation. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) may offer substantial protection across these domains compared with dipeptidyl peptidase-4 inhibitors (DPP4is), a commonly used alternative glucose-lowering therapy, a new study finds.

This nationwide retrospective cohort study is published in JAMA Network Open.

“This cohort study provides new evidence supporting the use of SGLT2is in patients with T2D and liver cirrhosis, demonstrating significant associations with reductions in the risks of ESKD [end-stage kidney disease], AKI [acute kidney injury], and MACE [major adverse cardiovascular event], as well as hepatic decompensation events,” wrote the researchers of the study. “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.”

T2D and liver cirrhosis frequently coexist and can worsen one another through shared metabolic and inflammatory pathways.² Insulin resistance and chronic hyperglycemia contribute to fat accumulation, fibrosis progression, and portal hypertension, while cirrhosis alters glucose metabolism and can impair insulin clearance, increasing the risk of worsening diabetes control. Patients with both conditions face higher risks of complications, including renal dysfunction, cardiovascular disease, infections, and mortality, making coordinated management essential.

The researchers conducted a retrospective cohort study using Taiwan’s National Health Insurance Database from May 2016 through December 2023. Adults diagnosed with both T2D and liver cirrhosis who newly initiated SGLT2is (dapagliflozin, empagliflozin, or canagliflozin) or DPP4is (alogliptin, linagliptin, sitagliptin, saxagliptin, or vildagliptin) were included.

The primary outcomes were ESKD, AKI, and MACE. Secondary outcomes included individual cardiovascular end points, hepatic decompensation events, and all-cause mortality.

The study included 24,259 patients (mean [SD] age, 64.68 [11.95] years; 33.9% female). Of these patients, 9689 patients (39.9%) received SGLT2is and 14,570 (60.1%) received DPP4is. Median follow-up was 2.3 years (IQR, 1.0-4.0).

Compared with DPP4i therapy, SGLT2i use was associated with significantly improved outcomes:

• ESKD: adjusted hazard ratio (aHR), 0.34; 95% CI, 0.25-0.47
• AKI: aHR, 0.66; 95% CI, 0.59-0.74
• MACE: aHR, 0.67; 95% CI, 0.62-0.71
• All-cause mortality: aHR, 0.58; 95% CI, 0.53-0.63
• Hepatic decompensation: aHR, 0.65; 95% CI, 0.57-0.74

Reductions were also observed across individual cardiovascular end points, reinforcing the cardioprotective profile of SGLT2is.

However, the researchers noted some limitations. Because this was an observational study, it cannot establish causality and may be subject to residual confounding despite statistical weighting. Findings were derived from a Taiwanese population, which may limit generalizability to other health systems and demographic groups. Additionally, detailed clinical measures such as cirrhosis severity, laboratory parameters, and lifestyle factors were not fully captured.

Despite these limitations, these findings highlight the potential cardiorenal and hepatic benefits of SGLT2is in a high-risk population with complex comorbid diseases, the authors stated.

“In this cohort study, we found that SGLT2is were associated with significantly lower risk of ESKD, AKI, MACE, and hepatic decompensation among patients with T2D and cirrhosis,” they wrote. “By interrupting key metabolic and hemodynamic pathways underlying T2D and liver disease, SGLT2is may offer meaningful clinical benefits for this high-risk population. Prospective studies are warranted to confirm these findings.”

References

1. Chung M, Yu T, Wu L, et al. SGLT2 inhibitor use and cardiorenal outcomes in type 2 diabetes with liver cirrhosis. JAMA Netw Open. 2026;9(2):e2560429. doi:10.1001/jamanetworkopen

2. Mohan A, Hasan ZW, Galani HG, et al. Diabetes and liver cirrhosis: shared pathways and clinical implications—a narrative review. Ann Med Surg (Lond). 2025;87(12):8418-8425. doi:10.1097/MS9.0000000000004012