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We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com. Back to Healio Key takeaways: GLP-1 use was associated with reduced hepatic complications in MASLD and type 2 diabetes. Reductions in hepatic complications were observed across FIB-4 and BMI groups among patients with MASLD. Use of GLP-1s was associated with significantly reduced risk for hepatic complications among patients with metabolic dysfunction-associated steatotic liver disease and type 2 diabetes, according to data. The observational study, published in The American Journal of Gastroenterology, showed that the reduction was prompted by fewer cases of incident cirrhosis. Researchers also found that GLP-1s may have a greater disease-modifying potential earlier in the fibrosis trajectory, before advanced fibrosis is established.
\u201cIt was intriguing to see both the magnitude and consistency of the benefit of GLP-1 treatment,\u201d lead author Erik Almazan, MD, resident physician at Brigham and Women\u2019s Hospital, told Healio. \u201cWe observed a 38% lower risk of hepatic complications in intention-to-treat analysis and a 42% lower risk in per-protocol analysis. \u201cThese findings suggest an exposure-response pattern consistent with a real biological effect with greater benefit observed during active treatment,\u201d he added. All of Us: GLP-1s, liver outcomes in MASLD Almazan and colleagues used NIH\u2019s All of Us dataset \u2014 a nationwide, sociodemographically diverse cohort \u2014 to examine long-term, real-world outcomes among individuals with MASLD and type 2 diabetes using GLP-1s compared with a propensity score-matched control group. The retrospective cohort study included 2,110 individuals (mean age, 55.8 years) on semaglutide (Wegovy, Novo Nordisk), liraglutide (Victoza\/Saxenda, Novo Nordisk), dulaglutide (Trulicity, Eli Lilly & Co.), exenatide, albiglutide, lixisenatide (Adlyxin, Sanofi) or tirzepatide (Mounjaro; Zepbound, Eli Lilly & Co.). They were matched with 2,110 nonusers (mean age, 56.9 years). All individuals were 18 years and older, and the majority were women and white. Data were collected from electronic health records, participant provided information and survey results from 2018 to 2023. Two analyses were conducted: an intention-to-treat analysis and per-protocol analysis. Subgroup analyses also looked at BMI and fibrosis-4 (FIB-4) scores (mean, 1.06 and 1.1). Median follow-up was 2.7 years. Individuals who had experienced hepatic complications, including prior cirrhosis, or other chronic liver diseases, were excluded. Other reasons for exclusion included prior exposure to GLP-1s, GLP-1 use less than 30 days, starting GLP-1s before MASLD diagnosis, no follow-up or having high risk FIB-4 scores (> 2.67). The primary outcome was a composite of hepatic complications, including incident cirrhosis, hepatocellular carcinoma, decompensation events and liver transplantation. Consistent liver benefit with GLP-1s Overall, 187 patients experienced hepatic complications in the intention-to-treat analysis. Of those, 74 events happened in GLP-1 users (95% CI, 10.59-16.94) and 113 happened in nonusers (95% CI, 18.02-26.29), corresponding to a 38% lower relative risk for hepatic complications among users (HR = 0.62; 95% CI, 0.46-0.83). Results were similar in the per-protocol analysis. GLP-1 users experienced 56 events (95% CI, 9.78-16.81) and the nonuser group had 113 (95% CI, 18.02-26.29), representing a 42% lower relative risk for complications among those using a GLP-1 medication (HR = 0.58; 95% CI, 0.42-0.8). \u201cThis complements data from randomized controlled trials that demonstrated histological benefits with GLP-1 receptor agonists but did not follow patients long enough to evaluate for clinical endpoints,\u201d Almazan said. \u201cOur findings extend those results to a more generalizable population.\u201d Compared with non-users, GLP-1 users reported sustained reductions in BMI and body weight over 5 years. The researchers noted that, on average, BMI declined by about 1 to 2 kg\/m\u00b2 while body weight decreased by approximately 3 to 8 kg. Additionally, GLP-1 use was associated with lower hazard estimates in the low FIB-4 group in both analyses, which has implications for \u201chow aggressively\u201d clinicians can identify and treat metabolic dysfunction in MASLD and type 2 diabetes, Almazan said. \u201cThe consistency of our findings where there was a directional benefit across FIB-4 strata and BMI categories also suggests that the hepatoprotective benefit of GLP-1 receptor agonists is not confined to a subset of patients and is likely applicable across the MASLD population, with the caveat that our study did not account specifically for participants with lean MASLD,\u201d Almazan said. Limitations noted in the study included limited follow-up, whether benefits continue with time or affect rates of outcomes such as HCC or liver transplant, and if the use of ICD codes instead of imaging or histology to assess fibrosis strata impacted results. In addition, because the All of Us Research Program includes volunteer participants, it has its \u201cown selection and surveillance bias considerations,\u201d Almazan said. He added that the program itself was worth highlighting: \u201cAll of Us deliberately aims to include racial and ethnic minorities as well as lower-income participants, demographic profiles that closely mirror the patients at highest risk for MASLD-related complications, and that are also often underrepresented in medical research including RCTs,\u201d he said. \u201cWe believe that demonstrating a benefit that holds after propensity score matching on socioeconomic variables is a meaningful addition to the existing literature.\u201d For more information: Erik Almazan, MD, can be reached at ealmazan@mgh.harvard.edu. Published by: Ask a clinical question and tap into Healio AI’s knowledge base.
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