RATIONALE: Obesity is a complex chronic condition linked to various comorbidities, such as hypertension, diabetes, and dyslipidaemia, with a significant global burden. Standard treatments, such as diet modifications and physical activity, often have limited effects and poor compliance. Pharmacological options, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), show promise for individuals with obesity. This is one of three reviews investigating GLP-1RAs for adults living with obesity.
OBJECTIVES: To assess the effects of liraglutide, a GLP-1RA, for adults living with obesity.
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, and two trials registries on 17 December 2024.
ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) that compared liraglutide at any dose with placebo or no treatment, structured lifestyle-modification programmes, other anti-obesity medications, or other GLP-1RAs, in adults with obesity, with a minimum follow-up of six months.
OUTCOMES: Critical outcomes were body weight, adverse events, major adverse cardiovascular events (MACE), quality of life, and mortality. Important outcomes were waist circumference, heart failure, diabetes-related outcomes, blood pressure-related outcomes, liver disease-related outcomes, obstructive sleep apnoea, and lipid metabolism-related outcomes. We prioritised critical outcomes for the main comparison of interest, liraglutide versus placebo, for the Abstract and key summary of findings tables.
RISK OF BIAS: We used the original Cochrane tool for assessing risk of bias (RoB 1).
SYNTHESIS METHODS: We synthesised results for each outcome using meta-analysis, where possible, with a random-effects model. We assessed the certainty of evidence for each outcome using GRADE.
INCLUDED STUDIES: We included 24 RCTs involving 9937 participants, aged 31.3 to 64.7 years, primarily from middle- and high-income countries. Most studies compared liraglutide to placebo, alone or within multi-arm designs (two studies included semaglutide as an active comparator, one included orlistat); two studies compared liraglutide versus structured lifestyle-modification programmes. Studies included participants with weight-related comorbidities; 17 focused on specific subgroups, including people with diabetes, non-alcoholic fatty liver disease, polycystic ovary syndrome, and obstructive sleep apnoea. All studies had medium-term follow-ups, and three also provided data at long-term follow-up. Twenty-two studies were funded by the drug manufacturer, with major involvement in design, conduct, analysis, or reporting in 13 studies.
SYNTHESIS OF RESULTS: Liraglutide versus placebo (medium-term: 26 to 68 weeks) The evidence is very uncertain about the effect of liraglutide on percentage weight change from baseline (mean difference (MD) -4.72, 95% confidence interval (CI) -5.32 to -4.12; I= 57%; 16 studies, 6050 participants; very low-certainty evidence), but likely increases the number of people achieving 5% weight reduction (risk ratio (RR) 2.10, 95% CI 1.80 to 2.45; I= 78%; 18 studies, 6651 participants; moderate-certainty evidence). Liraglutide may increase any adverse events (RR 1.07, 95% CI 1.04 to 1.11; I² = 28%; 16 studies, 8147 participants; low-certainty evidence) and serious adverse events (RR 1.20, 95% CI 1.00 to 1.43; I² = 0%; 20 studies, 8487 participants; low-certainty evidence). The evidence is very uncertain about the effects of liraglutide on non-serious adverse events (RR 1.14, 95% CI 1.05 to 1.24; I² = 76%; 17 studies, 7440 participants; very low-certainty evidence) and on adverse events leading to withdrawal (RR 1.98, 95% CI 1.30 to 3.02; I² = 47%; 19 studies, 8628 participants; very low-certainty evidence). Liraglutide likely results in little to no clinically meaningful difference in MACE (RR 0.86, 95% CI 0.66 to 1.10; I² = 0%; 6 studies, 5762 participants; moderate-certainty evidence). Liraglutide likely results in little to no difference in quality of life measured by the IWQOL-Lite-CT physical function (MD 2.90, 95% CI -0.08 to 5.89; I² = 58%; 6 studies, 3733 participants; moderate-certainty evidence). The evidence is very uncertain about the effect of liraglutide on mortality (RR 0.44, 95% CI 0.08 to 2.25; I² = 0%; 18 studies, 8224 participants; very low-certainty evidence). Liraglutide versus placebo (long-term: 104 to 162 weeks) Liraglutide may result in little to no clinically meaningful difference in percentage weight change from baseline (MD -4.34, 95% CI -5.26 to -3.43; I² = 0%; 2 studies, 1262 participants; low-certainty evidence), and likely increases the number of participants achieving 5% weight reduction (RR 1.78, 95% CI 1.51 to 2.09; I² = 0%; 2 studies, 1262 participants; moderate-certainty evidence). The evidence is very uncertain about the effect of liraglutide on any adverse events (RR 1.19, 95% CI 0.93 to 1.52; I² = 93%; 2 studies, 2640 participants; very low-certainty evidence) and on non-serious adverse events (RR 1.19, 95% CI 0.94 to 1.51; I² = 93%; 2 studies, 2640 participants; very low-certainty evidence). Liraglutide may increase serious adverse events (RR 1.20, 95% CI 0.98 to 1.48; I² = 0%; 2 studies, 2640 participants; low-certainty evidence) and adverse events leading to withdrawal (RR 2.16, 95% CI 1.59 to 2.93; I² = 0%; 2 studies, 2640 participants; low-certainty evidence). The evidence is very uncertain about the effect of liraglutide on MACE (RR 0.83, 95% CI 0.20 to 3.46; I² not applicable; 1 study, 2248 participants; very low-certainty evidence). Liraglutide likely results in little to no clinically meaningful difference in quality of life measured by the IWQoL-Lite-CT physical function (MD 3.81, 95% CI 1.03 to 6.59; I² not applicable; 1 study, 863 participants; moderate-certainty evidence). The evidence is very uncertain about the effect of liraglutide on mortality (RR 0.81, 95% CI 0.16 to 4.17; I² = 0%; 2 studies, 2640 participants; very low-certainty evidence). 2 2
AUTHORS' CONCLUSIONS: Liraglutide likely increases the proportion of people achieving at least 5% weight loss at medium-term follow-up; this effect is likely to be sustained at longer-term follow-up. Medium- or long-term impact on percentage weight change, MACE, quality of life, and mortality may be limited or uncertain. Liraglutide may lead to an increase in adverse events, including serious adverse events in both the medium and long term, which might further limit the sustainability of the initial effects. The drug manufacturer funded 22 studies, raising concerns about potential conflicts of interest. Further independent and long-term studies are needed to better understand the broader effects of liraglutide in the management of obesity.
FUNDING: World Health Organization (WHO) REGISTRATION: Original protocol (2022): DOI 10.1002/14651858.CD015092 Updated protocol (2025): PROSPERO CRD420250654193.
