Sodium-glucose inhibitors show similar hepatic effectiveness to GLP-1RAs in MASLD
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Key takeaways:
- Sodium-glucose inhibitors showed a similar risk for hepatic decompensation events vs. GLP-1RAs and a reduced risk vs. thiazolidinediones.
- Effectiveness was greater among women and those younger than 65 years.
Sodium-glucose cotransporter-2 inhibitors showed similar hepatic effectiveness to glucagon-like peptide-1 receptor agonists, especially among women and younger patients, in metabolic dysfunction-associated steatotic liver disease.
“Data from several RCTs have shown that [sodium-glucose cotransporter-2 inhibitors (SGLT-2i)] may have promising effects on fibrosis or steatosis, based on biological mechanisms of glucagon signaling pathways or insulin use reduction,” Sungho Bea, PharmD, PhD, a postdoctoral fellow in the division of pharmacoepidemiology and pharmacoecomonics at Brigham and Women’s Hospital and Harvard Medical School, and colleagues wrote in Gut. “A recent study that reported the hepatic effectiveness of glucose-lowering drugs in patients with MASLD did not include GLP-1RA, a class that is highly likely to be effective.
“Taken together, the hepatic benefits of SGLT-2i among patients with MASLD are inconclusive, warranting further investigations.”
In a population-based, head-to-head study, Bea and colleagues investigated the hepatic effectiveness of SGLT-2i compared with glucagon-like peptide-1 receptor agonists (GLP-1RA) and thiazolidinediones (TZD) in patients with MASLD.
The researchers included new users of one of the three treatments, using claims data from the National Health Insurance Service of Korea from September 2014 to December 2022. Following 1:1 propensity score matching, the final study population included 22,550 patients (median age, 57 years; 60% men) in the SGLT-2i vs. GLP-1RA cohort and 191,628 patients (median age, 57 years; 72% men) in the SGLT-2i vs. TZD cohort.
The primary outcome was a composite of hepatic decompensation events, which included ascites, esophageal varices with bleeding, hepatic failure or liver transplant. Additional outcomes included liver-related and all-cause mortality.
Over a mean follow-up of 2.1 years, the incidence rates of decompensation events were 10.61 vs. 14.21 per 1,000 person-years for SGLT-2i and GLP-1RA users, respectively, and 7.64 vs. 10.18 per 1,000 person-years, for SGLT-2i and TZD users. SGLT-2i demonstrated a similar risk for decompensation events compared with GLP-1RA (HR = 0.93; 95% CI, 0.76-1.14) and a reduced risk compared with TZD (HR = 0.77; 95% CI, 0.72-0.82), with similar results reported for secondary outcomes in both cohorts.
Further, the risk for decompensation events was lower with SGLT-2i vs. GLP-1RA when stratified by age (< 65 years: HR = 0.68; 95% CI, 0.52-0.9 vs. 65 years: HR = 1.37; 95% CI, 1.02-1.84) and vs. TZD when stratified by sex (men: HR = 0.87; 95% CI, 0.8-0.94 vs. women: HR = 0.62; 95% CI, 0.55-0.69).
“Use of SGLT-2i was associated with a lower risk of hepatic decompensation events in patients with MASLD compared with TZD, and importantly showed similar hepatic effectiveness to GLP-1RA,” Bea and colleagues wrote. “The hepatic effectiveness of SGLT-2i was greater in female patients and in patients aged less than 65 years.”
They continued: “Considering the established association between type 2 diabetes and liver disease, our findings provide real-world evidence supporting the role of SGLT-2i in patients with MASLD.”
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