Long Oral Presentation Nutrition Society of Australia 50th Annual Scientific Meeting 2026

Effects of semaglutide versus Mediterranean diet advice on dietary and circulating inflammatory markers in adults with metabolic dysfunction-associated steatotic liver disease: a secondary analysis. (145922)

Tonya Paris 1 , Ann M Farrell 2 3 , Marno Ryan 2 3 , Robin M Daly 1 , Gavin Abbott 1 , Shaun Mason 1 , Catherine Croagh 2 3 , Jessica Howell 2 3 4 5 , Alexander J Thompson 2 3 , James R Herbert 6 7 , Sherry Price 6 7 , Elena S George 1
  1. School of Exercise and Nutrition Sciences, Institute for Physical Activity and Nutrition, Deakin University, Geelong, 3220, Victoria, Australia
  2. Department of Medicine, University of Melbourne, Melbourne, 3010, Victoria, Australia
  3. Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, 3065, Victoria, Australia
  4. Disease Elimination, Burnet Institute, Melbourne, 3004, Victoria, Australia
  5. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, 3004, Victoria, Australia
  6. Department of Epidemiology and Biostatistics and Cancer Prevention and Control Program, Arnold School of Public Health, University of South Carolina, Columbia, 29206, South Carolina, United States of America
  7. Department of Nutrition, Connecting Health Innovations LLC (CHI), Columbia, 29201, South Carolina, United States of America

Obesity is associated with chronic systemic inflammation, which can contribute to multiple deleterious end-organ effects and chronic conditions, including Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) (1). Steatosis, inflammation, and hepatic fibrosis in MASLD can be improved following 5-10% weight loss (2). Glucagon-like peptide 1 receptor agonists lead to significant weight loss and improvements in insulin sensitivity and hepatic histology (3), but the impact of these drugs on diet quality and inflammatory markers in people with MASLD remains underexplored. The aim of this study was to explore the effects of 12-weeks of semaglutide compared to ongoing adherence to a Mediterranean diet (MedDiet) on the dietary inflammatory index (DII®) and circulating inflammatory markers following an initial intensive 12-week very low energy diet (VLED) or isocaloric MedDiet in overweight and obese participants with MASLD. This was a secondary analysis of a single-centre, two-arm randomised controlled trial in which 25 (44% female, mean age 50 years [27-67]) biopsy-proven MASLD participants were randomised to a 12-week VLED (n = 14) or isocaloric MedDiet (n = 11). Thereafter, VLED participants received weekly subcutaneous semaglutide (0.25-0.5 mg) for 12 weeks, while MedDiet participants continued this diet. DII and energy adjusted DII (E-DIITM) scores were derived from 3-day food diaries and serum inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], tumour necrosis factor-alpha [TNF-α], interleukin-6 [IL-6], adiponectin, and leptin) were assessed. Within-group differences assessed using paired t-tests and between-group differences assessed using linear regression. Overall, 23 participants (92%) completed the 24-week study. After the initial 12-week dietary interventions, no between-group differences were detected in dietary or circulating inflammatory markers. At 24 weeks, treatment with semaglutide was associated with a statistically significant net increase (worsening) in DII score [estimated mean difference: 1.6 (95% CI: 0.1, 3.2), p = 0.041] and E-DII [estimated mean difference: 1.4 (95% CI: 0.1, 2.7), p = 0.043] compared to MedDiet, due largely to a more pro-inflammatory diet in the semaglutide group [mean change from week 12 to 24; DII, 3.4 (95% CI: 2.2, 4.6), p < 0.001; E-DII, 3.4 (95% CI: 2.4, 4.4), p < 0.001]. The semaglutide group also had a significant increase in TNF-α from week 12 to 24 [mean change, 0.6 pg/mL (95% CI: 0.0, 1.1), p = 0.037] and a reduction in leptin from baseline to week 24 [mean change, -7.8 ng/mL (95% CI: -14.3, -1.3), p = 0.023), due to a significant reduction after the initial 12-week VLED intervention with no further changes from 12 to 24 weeks. In conclusion, in overweight/obese adults with MASLD, 12 weeks of treatment with semaglutide following a 12-week VLED was associated with adverse changes towards a more pro-inflammatory diet compared to those maintaining a MedDiet, but there were no changes in circulating inflammatory markers.

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