Randomized trial comparing effects of weight loss by liraglutide with lifestyle modification in non‐alcoholic fatty liver disease
Abstract
BACKGROUND & AIMS: We compared the effects of weight loss induced with the glucagon-like peptide-1 agonist liraglutide, with that of lifestyle modification, followed by weight maintenance after discontinuing intervention, in obese adults with non-alcoholic fatty liver disease (NAFLD). METHODS: , 90% male) adults with NAFLD defined as liver fat fraction (LFF) > 5% on magnetic resonance imaging without other causes of hepatic steatosis were randomized to a supervised programme of energy restriction plus moderate-intensity exercise to induce ≥ 5% weight loss (DE group, n = 15), or liraglutide 3 mg daily (LI group, n = 15) for 26 weeks, followed by 26 weeks with only advice to prevent weight regain. RESULTS: Diet and exercise and LI groups had significant (P < 0.01) and similar reductions in weight (-3.5 ± 3.3 vs -3.0 ± 2.2 kg), LFF (-8.1 ± 13.2 vs -7.0 ± 7.1%), serum alanine aminotransferase (-39 ± 35 vs -26 ± 33 U/L) and caspase-cleaved cytokeratin-18 (cCK-18) (-206 ± 252 vs -130 ± 158 U/L) at 26 weeks. At 52 weeks, the LI group significantly (P < 0.05) regained weight (1.8 ± 2.1 kg), LFF (4.0 ± 5.3%) and cCK-18 (72 ± 126 U/L), whereas these were unchanged in the DE group. CONCLUSIONS: Liraglutide was effective for decreasing weight, hepatic steatosis and hepatocellular apoptosis in obese adults with NAFLD, but benefits were not sustained after discontinuation, in contrast with lifestyle modification. Continuing the exercise learned in the structured programme contributed to the maintenance of liver fat reduction.
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In those studies, immediately following treatment, the reductions in weight and liver fat content were similar.
“Immediately following treatment, and similar to our observations, the reductions in weight and liver fat content were similar”
From Randomised trial comparing weight loss through lifestyle and GLP-1 receptor agonist therapy in people with MASLD (2025) · cites this paper as [28]
Two published studies have used higher doses of liraglutide (3 mg) with a 26-week intervention period.
“Two published studies have used higher doses of liraglutide (3 mg) with a 26-week intervention period.”
From Randomised trial comparing weight loss through lifestyle and GLP-1 receptor agonist therapy in people with MASLD (2025) · cites this paper as [28]
There was increased weight regain in the liraglutide-treated group compared with the lifestyle intervention arm in those studies.
“there was increased weight regain in the liraglutide-treated group compared with the lifestyle intervention arm.28,29”
From Randomised trial comparing weight loss through lifestyle and GLP-1 receptor agonist therapy in people with MASLD (2025) · cites this paper as [28]
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- Authors
- Khoo, J., Hsiang, J. C., Taneja, R., Koo, S., Soon, G., Kam, C. J., Law, N., & Ang, T.
- Affiliations
- Changi General Hospital (SG)
- Corresponding author
- Khoo, Joan
- Venue
- Liver International
- Publisher
- Wiley
- Published
- 2019-02-24
- Volume
- 39
- Issue
- 5
- Pages
- 941-949
- ISSN
- 0106-9543 (ISSN-L)
- 1478-3223
- 1478-3231
- OpenAlex
- W2913917435
- Cited by
- 136
- References
- 42
- Citations by year
- 2026: 21 · 2025: 28 · 2024: 21 · 2023: 18 · 2022: 18 · 2021: 16 · 2020: 7 · 2019: 7
- FWCI
- 9.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Liver International (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Medical Research Council (NMRC/CG/002/2013)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- liraglutide, non-alcoholic fatty liver disease, weight loss, lifestyle modification, caloric restriction, physical activity, GLP-1 receptor agonists, hepatic steatosis, liver fat fraction, hepatocyte apoptosis, caspase-cleaved cytokeratin 18, weight regain, obesity
- MeSH terms
- Liraglutide, Healthy Lifestyle, Adult, Female, Humans, Hypoglycemic Agents, Liver, Male, Middle Aged, Obesity, Prospective Studies, Singapore, Weight Loss, Exercise, Body Mass Index, Non-alcoholic Fatty Liver Disease
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