GLP-1RAs, SGLT-2 Inhibitors Tied to Lower Adverse Cardiovascular and Liver Events in Persons with T2D, MASLD

Compared to other diabetes treatments, use of glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium–glucose cotransporter 2 inhibitors (SGLT-2is) reduce the risk of major adverse cardiovascular (CV) events and serious liver events among individuals with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD), according to new data.¹

Findings from 2 analyses were presented at ENDO 2024, the Endocrine Society’s annual meeting, held June 1-4 in Boston, Massachusetts.

“Before this study, there was limited information about how these specific diabetes medications work in patients with both type 2 diabetes and [MASLD],” presenting author Alexander Kutz, MPD, MH, MSc, research fellow, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, said in a press release.“Our study shows that GLP-1 receptor agonists and SGLT-2 inhibitors are more beneficial in preventing heart-related events compared to another group of drugs such as dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors), and GLP-1s also help reduce severe liver events.”²

To examine the CV and hepatic effectiveness and safety of GLP-1RAs and SGLT-2is in patients with T2D and known MASLD, Kutz and colleagues conducted 2 weighted cohort studies in this patient population who initiated therapy with either GLP-1RA (n=13 666), SGLT-2i (n=11 108), or DDP-4i (n=17 084). They used pooled data from Medicare documented between 2013 and 2020 and a large US health insurance database from 2013 to 2022.¹

According to the study abstract, the primary CV effectiveness outcome was a composite of acute myocardial infarction, ischemic stroke, hospitalization for heart failure, or all-cause mortality. Also, the primary hepatic effectiveness outcome was a composite of serious liver events (eg, hospitalization for ascites, spontaneous bacterial peritonitis, hepatorenal syndrome) and the safety outcome was a composite of severe adverse events, such as lower limb amputation, emergency admission for hypoglycemia, and nonvertebral fracture.¹

GLP-1RAs and SGLT-2is associated with fewer CV events. Researchers observed that compared with DPP-4i treatment, the HR for the primary CV outcome associated with GLP-1RA agents was 0.67 (95% CI 0.56-0.81), which corresponds to an incidence rate difference (IRD) per 1000 person-years of -21.6 (95% CI 26.7 to -16.6). They also noted CV benefits for SGLT-2i use compared with DPP-4i use, with an HR for the primary CV outcome of 0.82 (95% CI 0.70-0.96) and an IRD of -11 (95% CI -16.2 to -5.8).¹

GLP-1RAs lowered serious liver events. Investigators noted that GLP-1RAs reduced severe liver events compared to DPP-4is, with an HR for the primary hepatic outcome of 0.47 (95% CI 0.25-0.90) and an IRD of -2.1 (95% CI -3.4 to -0.9). Among the SGLT-2i arm, the HR was 0.81 (95% CI 0.45-1.44) and an IRD of -1.1 (95% CI -2.4 to 0.3).¹

Serious adverse events. Kutz and colleagues added that severe adverse events were not more frequent with the use of GLP-1RAs or SGLT-2is compared with DPP-4is.¹

“An increasing amount of people live with type 2 diabetes, and a significant proportion of these individuals also struggle with MASLD,” Kutz stated in the release. “Understanding which medications can effectively manage these conditions and prevent severe complications is crucial for their health and quality of life.”²

References:

1. Kutz A, Wexler DJ, Liu J, Paik JM, Patorno E. Association of GLP-1 receptor agonists and SGLT-2 inhibitors with major adverse cardiovascular events and serious liver events among patients with type 2 diabetes and MASLD. Presented at: ENDO 2024; June 1-4, 2024; Boston, MA. Accessed June 4, 2024.
2. Two medication classes reduced cardiovascular and liver events in people with type 2 diabetes. News item. Endocrine Society. June 2, 2024. Accessed June 4, 2024. https://www.endocrine.org/news-and-advocacy/news-room/2024/endo-2024-press-kutz