Anti-obesity medications (AOMs) are used with lifestyle change support for weight management for adults with obesity. We investigated whether initiation of AOMs appeared to reduce attempted lifestyle changes. We searched for orlistat, liraglutide, semaglutide, and low-fat reducing diet (LFRD) trials in a trial register, Medline, Embase and systematic reviews from 1990 to June 2023. Weight changes in placebo groups of AOM trials with lifestyle interventions were compared to weight changes in LFRD trials. 16 orlistat, 7 liraglutide, 5 semaglutide, and 7 LFRD trials were included. Weight loss in orlistat placebo groups was 1.1kg less than LFRDs, a statistically non-significant difference, where last observation carried forward values were used for missing data in trials. Adjustment with baseline observation carried forward found 2.6kg less weight lost, a significant difference. Last observation carried forward data for orlistat trials providing completer data found a 0.2kg difference. Liraglutide placebo groups had 2.1kg less weight lost than predicted from LFRD trials. Semaglutide placebo groups had 2.0kg less weight loss. Compensatory reductions in changes to lifestyle behaviours may result following AOM initiation, but this needs to be explored further. Variability in trial design and study populations may contribute to the differences in weight change found. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Health and Social Care Directorates. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Abbenhardt et al. 2013 https://doi.org/10.1111/joim.12062, Anderssen et al. 1995. Oslo Diet and Exercise Study: a one year randomized intervention trial. Effect on hemostatic variables and other coronary risk factors. Nutrition Metabolism and Cardiovascular Diseases vol 5. Astrup et al. 2012 https://doi.org/10.1038/ijo.2011.158 Bakris et al. 2002 https://doi.org/10.1097/00004872-200211000-00026 Berne 2005 https://doi.org/10.1111/j.1464-5491.2004.01474.x Broom et al. 2002 http://www.ncbi.nlm.nih.gov/pubmed/12296610 Davidson et al. 1999 https://doi.org/10.1001/jama.281.3.235 Davies et al. 2021 https://doi.org/10.1016/S0140-6736(21)00213-0 Davies et al. 2015 https://doi.org/10.1001/jama.2015.9676 Finer et al. 2000 https://doi.org/10.1038/sj.ijo.0801128 Garvey et al. 2022 https://doi.org/10.1038/s41591-022-02026-4 Garvey et al. 2020 https://doi.org/10.2337/dc19-1745 Hauptman et al. 2000 https://doi.org/10.1001/archfami.9.2.160 Hollander et al. 1998 https://doi.org/10.2337/diacare.21.8.1288 Jones et al. 1999 https://doi.org/10.1016/S0895-7061(99)00123-5 Kadowaki et al. 2022 https://doi.org/10.1016/S2213-8587(22)00008-0 Kelley et al. 2002 https://doi.org/10.2337/diacare.25.6.1033 Krempf et al. 2003 https://doi.org/10.1038/sj.ijo.0802281 Lim et al. 2010 https://doi.org/10.1016/j.numecd.2009.05.003 Lindgarde 2000 https://doi.org/10.1046/j.1365-2796.2000.00720.x Miles et al. 2002 https://doi.org/10.2337/diacare.25.7.1123 O Neil et al. 2018 https://doi.org/10.1016/S0140-6736(18)31773-2 Pi-Sunyer et al. 2015 https://doi.org/10.1056/nejmoa1411892 Pritchard et al. 1999. https://doi.org/10.1136/jech.53.5.311 Rossner et al. 2000 https://doi.org/10.1038/oby.2000.8 Rubino et al. 2022 https://doi.org/10.1001/jama.2021.23619 Sjostrom et al. 1998 https://doi.org/10.1016/S0140-6736(97)11509-4 Swinburn et al. 2005 https://doi.org/10.1111/j.1463-1326.2004.00467.x Swinburn et al. 2001 https://doi.org/10.2337/diacare.24.4.619 Torgerson et al. 2004 https://doi.org/10.2337/diacare.27.1.155 Wadden et al. 2020 https://doi.org/10.1002/oby.22726 Wilding et al. 2021 https://doi.org/10.1056/nejmoa2032183 Wood et al. 1991 https://doi.org/10.1056/NEJM199108153250703 I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data used are available from the following papers: Abbenhardt et al. 2013 , Anderssen et al. 1995. Oslo Diet and Exercise Study: a one year randomized intervention trial. Effect on hemostatic variables and other coronary risk factors. Nutrition Metabolism and Cardiovascular Diseases vol 5. Astrup et al. 2012 , Bakris et al. 2002 , Berne 2005 , Broom et al. 2002 , Davidson et al. 1999 , Davies et al. 2021 , Davies et al. 2015 Finer et al. 2000 Garvey et al. 2022 Garvey et al. 2020 Hauptman et al. 2000 Hollander et al. 1998 Jones et al. 1999 Kadowaki et al. 2022 Kelley et al. 2002 Krempf et al. 2003 Lim et al. 2010 Lindgarde 2000 Miles et al. 2002 O Neil et al. 2018 Pi-Sunyer et al. 2015 Pritchard et al. 1999. Rossner et al. 2000 Rubino et al. 2022 Sjostrom et al. 1998 Swinburn et al. 2005 Swinburn et al. 2001 Torgerson et al. 2004 Wadden et al. 2020 Wilding et al. 2021 Wood et al. 1991 All data produced in the present work are contained in the manuscript * PA : physical activity AOM : anti-obesity medications GLP-1 : glucagon-like peptide-1 LLD : lipid lowering drugs RCT : randomised controlled trial kcal : kilocalorie BMI : body mass index LFRD : low-fat reducing diet kg : kilogram SD : standard deviation LOCF : last observation carried forward RR : risk ratio CI : confidence interval BOCF : baseline observation carried forward