SGLT2 inhibitors linked to fewer cardio-hepatic events
In adults with metabolic dysfunction–associated steatotic liver disease, sodium-glucose cotransporter-2 inhibitors were associated with lower death, hospital stays, heart events, and liver complications.
*Retrospective matched cohort study; Level 2b (OCEBM).

Citation

Pham HN, Ibrahim R, Mouhaffel R, et al. SGLT2 inhibitors and cardiovascular outcomes in metabolic dysfunction-associated steatotic liver disease: A real-world retrospective cohort study. The American Journal of Medicine. 2026;139:57–65. doi:10.1016/j.amjmed.2025.06.039.

Background

Metabolic dysfunction–associated steatotic liver disease is common and is linked to higher risk of heart disease and death. This study tested whether sodium-glucose cotransporter-2 inhibitors are associated with better heart and liver outcomes in routine care.

Patients

Adults (≥18 years) with metabolic dysfunction–associated steatotic liver disease in the TriNetX network (2014–2022); excluded prior alcohol-associated liver disease.

Intervention

Use of sodium-glucose cotransporter-2 inhibitors after liver disease diagnosis.

Control

No sodium-glucose cotransporter-2 inhibitor use; groups matched 1:1 on baseline factors (69,970 per group).

Outcome

(Primary) All-cause death; all-cause hospitalization. Heart, liver, and kidney outcomes were also assessed.

Follow-up Period

Mean 3.70 years (users) vs 4.14 years (non-users).

Results

Outcome Users vs non-users Risk over time NNT
All-cause death (primary)7.7% vs 14.0%HR 0.60 (0.58–0.62)16
All-cause hospitalization (primary)49.6% vs 58.1%HR 0.79 (0.78–0.80)12
Heart failure flare-up14.4% vs 17.2%HR 0.87 (0.85–0.90)36
Heart attack7.1% vs 8.4%HR 0.92 (0.88–0.95)77
Ischemic stroke5.9% vs 6.8%HR 0.95 (0.92–0.99)112
Cardiac arrest1.3% vs 2.2%HR 0.66 (0.61–0.72)112
Acute liver failure1.1% vs 1.7%HR 0.70 (0.64–0.77)167
Cirrhosis6.6% vs 7.9%HR 0.90 (0.86–0.94)77
Acute kidney injury18.1% vs 23.3%HR 0.80 (0.78–0.82)19
HR = hazard ratio; NNT = number needed to treat (approximate, from absolute risk differences).

Limitations

Retrospective database study: cannot prove cause and effect, and diagnosis coding may be inaccurate. Unmeasured differences may remain despite matching. Some benefits were small in absolute terms (high NNT for stroke, liver failure, and cardiac arrest). Drug dose and duration were not available.

Funding

No specific grant funding; authors reported no competing interests.

Clinical Application

For patients with this liver disease (often with diabetes), consider these drugs when otherwise appropriate; benefits appear broad, but randomized trials are needed.