Glucose-lowering therapies linked to reduced risk for CV events in type 2 diabetes, MASLD
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Key takeaways:
- Sodium-glucose cotransporter-2 inhibitors correlated with lower risk for major adverse CV events across MASLD status.
- Glucagon-like peptide-1 receptor agonists benefit those with type 2 diabetes and MASLD.
Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists were associated with lower risk for cardiovascular events in type 2 diabetes, with or without metabolic dysfunction-associated steatotic liver disease.
“Glucose-lowering medications, such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), have shown cardiorenal benefits beyond blood glucose control,” Sungho Bea, PharmD, of the School of Pharmacy at Sungkyunkwan University, and colleagues wrote in JAMA Network Open. “Moreover, several studies have demonstrated the potential hepatic benefits of these drugs across the spectrum of liver disease including liver steatosis, liver fibrosis and hepatocellular carcinoma.”
They continued: “Despite the established biological mechanisms of these novel glucose lowering medication classes, their clinical effectiveness among patients with both NAFLD and T2D remains unknown.”
In a retrospective, population-based, nationwide cohort study, Bea and colleagues compared outcomes among patients with type 2 diabetes who began therapy with SGLT-2i or GLP-1RA vs. those treated with dipeptidyl peptidase-2 inhibitors (DPP-4i). Before propensity score matching, 214,453 patients treated with SGLT-2i or GLP-1RA had MASLD and 466,674 did not.
The final active-comparator, matched cohorts included 140,438 patients (mean age, 57.5 years; 56.7% men) in the SGLT-2i vs. DPP-4i group and 34,886 patients (mean age, 59.5 years; 51.3% men) in the GLP-1RA vs. DPP-4i group.
Primary studied outcomes included major adverse CV events (MACE) — a composite of hospitalization for myocardial infarction, stroke and CV death — and hospitalization for heart failure (HFF). Other outcomes included the individual components of MACE and all-cause mortality.
According to results, SGLT-2i therapy was associated with a decreased risk for MACE compared with DPP-4is (HR = 0.78; 95% CI, 0.71-0.85), which remained consistent across MASLD status. Although the risk for HHF also was lower with SGLT-2i in the overall study population (HR = 0.62; 95% CI, 0.48-0.81), the reduction was not statistically significant among those with MASLD.
Results also showed that GLP-1RA therapy was associated with a 51% decreased risk for MACE in the overall population compared with DPP-4i (HR = 0.49; 95% CI, 0.39-0.77), which was consistent across MASLD status. GLP-1RA was not associated with a lower risk for HHF in the overall population (HR = 0.64; 95% CI, 0.39-1.07), with similar results reported by MASLD status.
“This population-based cohort study found that GLP-1RA and SGLT-2i therapy were associated with reduced risk of MACE in patients with T2D and across baseline NAFLD status,” Bea and colleagues wrote. “Moreover, SGLT-2is were associated with reduced risk of HHF.”
They concluded: “These results support the current guidelines that recommend GLP-1RA as the first-line of therapy for patients with T2D and NAFLD. Furthermore, this study highlights the potential of SGLT-2i as a promising option for cardiovascular disease prevention regardless of NAFLD status.”
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