Sodium-glucose cotransporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) therapies are associated with decreased risk for major adverse cardiovascular events (MACE) among patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD), according to study findings published in JAMA Network Open.

The presence of MASLD is associated with higher cardiovascular disease (CVD) risk and is more common among patients with T2D than the general population. Both MASLD and T2D share multiple risk factors and interfere with glycemic control. Glucose-lowering medications have been associated with cardiorenal benefits; however, no studies have evaluated the effect these therapies have on CVD risk among patients with MASLD.

Data for this study were sourced from the National Health Insurance Service (NHIS). Between 2014 and 2020, new users of SGLT2is or GLP-1RAs were propensity matched 1:1 with patients who initiated dipeptidyl peptidase-4 inhibitors (DPP-4is). The primary outcomes were heart failure (HF) hospitalization and MACE, defined as the composite of hospitalization for myocardial infarction or stroke and cardiovascular death.

A total of 214,453 patients with MASLD and 466,674 without MASLD were new users of SGLT2is. After propensity matching with new DPP-4i users, 70,219 individuals comprised each group. The SGLT2i and DPP-4i patient groups had a mean age of 57.6 and 57.4 years, 56.5% and 56.9% were men, and 27.8% and 28.3% had a Charlson comorbidity index (CCI) of 0, respectively.

Compared with DPP-4i, use of SGLT2i associated with decreased risk for MACE among users with (HR, 0.73; P <.001) and without (HR, 0.81; P <.001) MASLD and HF hospitalizations among users without MASLD (HR, 0.56).

Use of SGLT2i was favored over DPP-4i for secondary outcomes of stroke (HR, 0.70), cardiovascular-related mortality (HR, 0.54), and all-cause mortality (HR, 0.52) among the pooled population and among groups with (HR range, 0.38-0.62) and without (HR range, 0.55-0.75) MASLD.

A total of 234,836 patients with MASLD and 546,568 without MASLD were new users of GLP-1RAs. After propensity matching with new DPP-4i users, 17,443 individuals comprised each group. The GLP-1RA and DPP-4i patient groups had a mean age of 59.5 and 59.5 years, 51.3% and 51.3% were men, and 11.0% and 10.7% had a CCI of 0, respectively.

Use of GLP-1RA was associated with decreased risk for MACE among GLP-1RA users with (HR, 0.49; P =.001) and without (HR, 0.49; P <.001) MASLD, but not with decreased risk for HF hospitalizations.

For the secondary outcomes, GLP-1RA use was associated with improved stroke (HR, 0.44), cardiovascular mortality (HR, 0.46), and all-cause mortality (HR, 0.37) outcomes in the pooled study population. However, a significant interaction was observed for the all-cause mortality outcome (P =.008), in which the beneficial effect of GLP-1RA was much stronger among patients with MASLD (HR, 0.15) than without MASLD (HR, 0.47).

“These results support the current guidelines that recommend GLP-1RA as the first-line of therapy for patients with T2D and NAFLD,” study authors noted. “Furthermore, this study highlights the potential of SGLT-2i as a promising option for cardiovascular disease prevention regardless of NAFLD status.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Gastroenterology Advisor