{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:25:44Z","timestamp":1786969544006,"version":"build-2736575974"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":5,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["ICI20\/00043"],"award-info":[{"award-number":["ICI20\/00043"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004895","name":"Fondo Social Europeo","doi-asserted-by":"publisher","award":["FI23\/00061"],"award-info":[{"award-number":["FI23\/00061"]}],"id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004895","name":"Fondo Social Europeo","doi-asserted-by":"publisher","award":["CM25\/00014"],"award-info":[{"award-number":["CM25\/00014"]}],"id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004895","name":"Fondo Social Europeo","doi-asserted-by":"publisher","award":["CM24\/0182"],"award-info":[{"award-number":["CM24\/0182"]}],"id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Weight gain is a major complication of contemporary antiretroviral treatment (ART). We evaluated the effects of metformin on weight trajectories and metabolic outcomes in non-diabetic, non-obese, older persons with HIV-1 (PWH).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this double-blind, randomized, placebo-controlled pilot trial (METFORAGING), PWH 50\u2005years or older, virologically suppressed, without diabetes or insulin resistance, were randomly assigned (1:1) to metformin 850\u2005mg or placebo twice daily for 96\u2005weeks at La Paz University Hospital (Madrid, Spain). This prespecified secondary analysis evaluated changes in body weight, body mass index (BMI), glycemic indices, lipid parameters, and serum growth differentiation factor-15 (GDF-15) in the per-protocol population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Forty participants were randomly assigned (metformin n = 19; placebo n = 21); 35 completed treatment through week 96 (per-protocol population). At week 96, mean weight change was \u22121.5\u2005kg (95% CI \u22122.9 to \u22120.03) with metformin and +1.3\u2005kg (\u22120.7 to 3.3) with placebo (between-group difference \u22122.8\u2005kg [95% CI \u22125.2 to \u22120.4]; P = .025). After discontinuation, weight in the metformin group returned toward baseline (between-group difference from week 96 to 144: 2.2\u2005kg [95% CI 0.05 to 4.5]; P = .045). At week 96, changes in body weight correlated inversely with changes in serum GDF-15 in the metformin group (r = \u22120.67; P = .003). No serious adverse events were attributed to metformin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Metformin attenuated weight gain in nondiabetic, nonobese PWH receiving contemporary ART, but the effect was not sustained after discontinuation. These findings support larger trials to confirm efficacy and define optimal treatment duration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>EudraCT 2021-003299-15 (https:\/\/www.clinicaltrialsregister.eu).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ofid\/ofag489","type":"journal-article","created":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T11:33:47Z","timestamp":1785670427000},"source":"Crossref","is-referenced-by-count":0,"title":["Metformin and Weight Changes in Non-diabetic Older People With HIV (METFORAGING): A Double-Blind, Randomized, Placebo-Controlled, Pilot Trial"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6187-7442","authenticated-orcid":false,"given":"Cristina","family":"Marcelo-Calvo","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, HIV Unit, La Paz University Hospital , Madrid ,","place":["Spain"]},{"name":"Hospital La Paz Institute for Health Research (IdiPAZ) , Madrid ,","place":["Spain"]},{"name":"CIBER of Infectious Diseases (CIBERINFEC) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"Esteban-Cantos","sequence":"additional","affiliation":[{"name":"Hospital La Paz Institute for Health Research (IdiPAZ) , Madrid ,","place":["Spain"]},{"name":"CIBER of Infectious Diseases (CIBERINFEC) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Jurado","sequence":"additional","affiliation":[{"name":"Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3446-0545","authenticated-orcid":false,"given":"Roc\u00edo","family":"Montejano","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, HIV Unit, La Paz University Hospital , Madrid ,","place":["Spain"]},{"name":"Hospital La Paz Institute for Health Research (IdiPAZ) , Madrid ,","place":["Spain"]},{"name":"CIBER of Infectious Diseases (CIBERINFEC) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Guti\u00e9rrez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Hospital La Paz Institute for Health Research (IdiPAZ) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"de Gea-Grela","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, HIV Unit, La Paz University Hospital , Madrid ,","place":["Spain"]},{"name":"Hospital La Paz Institute for Health Research (IdiPAZ) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Mart\u00ednez-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, HIV Unit, La Paz University Hospital , Madrid ,","place":["Spain"]},{"name":"Hospital La Paz Institute for Health Research (IdiPAZ) , Madrid ,","place":["Spain"]},{"name":"CIBER of Infectious Diseases (CIBERINFEC) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2609-2559","authenticated-orcid":false,"given":"Alejandro","family":"D\u00edez-Vidal","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, HIV Unit, La Paz University Hospital , Madrid ,","place":["Spain"]},{"name":"Hospital La Paz Institute for Health Research (IdiPAZ) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"de Miguel Buckley","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, HIV Unit, La Paz University Hospital , Madrid ,","place":["Spain"]},{"name":"Hospital La Paz Institute for Health Research (IdiPAZ) , Madrid ,","place":["Spain"]},{"name":"CIBER of Infectious Diseases (CIBERINFEC) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos M","family":"O\u00f1oro-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, HIV Unit, La Paz University Hospital , Madrid ,","place":["Spain"]},{"name":"Hospital La Paz Institute for Health Research (IdiPAZ) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Hospital La Paz Institute for Health Research (IdiPAZ) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luz","family":"Mart\u00edn-Carbonero","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, HIV Unit, La Paz University Hospital , Madrid ,","place":["Spain"]},{"name":"Hospital La Paz Institute for Health Research (IdiPAZ) , Madrid ,","place":["Spain"]},{"name":"CIBER of Infectious Diseases (CIBERINFEC) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 I","family":"Bernardino","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, HIV Unit, La Paz University Hospital , Madrid ,","place":["Spain"]},{"name":"Hospital La Paz Institute for Health Research (IdiPAZ) , Madrid ,","place":["Spain"]},{"name":"CIBER of Infectious Diseases (CIBERINFEC) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo Men\u00e9ndez","family":"Colino","sequence":"additional","affiliation":[{"name":"Hospital La Paz Institute for Health Research (IdiPAZ) , Madrid ,","place":["Spain"]},{"name":"Department of Geriatrics, La Paz University Hospital , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noem\u00ed Gonz\u00e1lez P\u00e9rez","family":"de Villar","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, La Paz University Hospital , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berta","family":"Rod\u00e9s","sequence":"additional","affiliation":[{"name":"Hospital La Paz Institute for Health Research (IdiPAZ) , Madrid ,","place":["Spain"]},{"name":"CIBER of Infectious Diseases (CIBERINFEC) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7410-9450","authenticated-orcid":false,"given":"Jos\u00e9 R","family":"Arribas","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, HIV Unit, La Paz University Hospital , Madrid ,","place":["Spain"]},{"name":"Hospital La Paz Institute for Health Research (IdiPAZ) , Madrid ,","place":["Spain"]},{"name":"CIBER of Infectious Diseases (CIBERINFEC) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"2026081707364175500_ofag489-B1","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1093\/cid\/ciae191","article-title":"Antiretrovirals and weight change: weighing the evidence","volume":"79","author":"Wohl","year":"2024","journal-title":"Clin Infect Dis"},{"key":"2026081707364175500_ofag489-B2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s11904-022-00642-w","article-title":"Diabetes in HIV: the link to weight gain","volume":"20","author":"Bailin","year":"2023","journal-title":"Curr HIV\/AIDS Rep"},{"key":"2026081707364175500_ofag489-B3","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2018.00705","article-title":"The impact of weight gain during HIV treatment on risk of pre-diabetes, diabetes mellitus, cardiovascular disease, and mortality","volume":"9","author":"Kumar","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2026081707364175500_ofag489-B4","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1093\/cid\/ciae449","article-title":"Define: a prospective, randomized, phase 4 trial to assess a protease inhibitor-based regimen switch strategy to manage integrase inhibitor-related weight gain","volume":"80","author":"Anderson","year":"2025","journal-title":"Clin Infect Dis"},{"key":"2026081707364175500_ofag489-B5","doi-asserted-by":"crossref","first-page":"e81","DOI":"10.1093\/cid\/ciag196","article-title":"A 48-week, randomized controlled trial of doravirine for individuals with HIV, and obesity on integrase inhibitors and Tenofovir Alafenamide: The Do IT Study (ACTG A5391)","volume":"83","author":"Koethe","year":"2026","journal-title":"Clin Infect Dis"},{"key":"2026081707364175500_ofag489-B6","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/S2213-8587(24)00150-5","article-title":"Once-weekly semaglutide in people with HIV-associated lipohypertrophy: a randomised, double-blind, placebo-controlled phase 2b single-centre clinical trial","volume":"12","author":"Eckard","year":"2024","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2026081707364175500_ofag489-B7","doi-asserted-by":"crossref","first-page":"e544","DOI":"10.1093\/cid\/ciaf652","article-title":"The bounce-back effect: what happens after cessation of low-dose semaglutide in people with HIV","volume":"82","author":"Erlandson","year":"2026","journal-title":"Clin Infect Dis"},{"key":"2026081707364175500_ofag489-B8","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2025.2964","article-title":"Spending on glucagon-like peptide-1 receptor agonists among US adults","volume":"8","author":"Tsipas","year":"2025","journal-title":"JAMA Netw Open"},{"key":"2026081707364175500_ofag489-B9","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.cmet.2023.03.014","article-title":"Metformin triggers a kidney GDF15-dependent area postrema axis to regulate food intake and body weight","volume":"35","author":"Zhang","year":"2023","journal-title":"Cell Metab"},{"key":"2026081707364175500_ofag489-B10","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1210\/endrev\/bnaa023","article-title":"Cellular and molecular mechanisms of metformin action","volume":"42","author":"Lamoia","year":"2021","journal-title":"Endocr Rev"},{"key":"2026081707364175500_ofag489-B11","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1111\/dom.15501","article-title":"The impact of metformin on weight and metabolic parameters in patients with obesity: a systematic review and meta-analysis of randomized controlled trials","volume":"26","author":"Haber","year":"2024","journal-title":"Diabetes Obes Metab"},{"key":"2026081707364175500_ofag489-B12","doi-asserted-by":"crossref","first-page":"682","DOI":"10.7326\/M18-1605","article-title":"Long-term weight loss with metformin or lifestyle intervention in the Diabetes Prevention Program Outcomes Study","volume":"170","author":"Apolzan","year":"2019","journal-title":"Ann Intern Med"},{"key":"2026081707364175500_ofag489-B13","doi-asserted-by":"crossref","first-page":"4611","DOI":"10.1210\/jc.2002-020709","article-title":"Sustained benefits of metformin therapy on markers of cardiovascular risk in human immunodeficiency virus-infected patients with fat redistribution and insulin resistance","volume":"87","author":"Hadigan","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2026081707364175500_ofag489-B14","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1007\/s40200-021-00869-1","article-title":"The effect of metformin on body mass index and metabolic parameters in non-diabetic HIV-positive patients: a meta-analysis","volume":"20","author":"Harmooshi","year":"2021","journal-title":"J Diabetes Metab Disord"},{"key":"2026081707364175500_ofag489-B15","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1007\/s00125-023-05968-7","article-title":"Metformin for the prevention of diabetes among people with HIV and either impaired fasting glucose or impaired glucose tolerance (prediabetes) in Tanzania: a Phase II randomised placebo-controlled trial","volume":"66","author":"Garrib","year":"2023","journal-title":"Diabetologia"},{"key":"2026081707364175500_ofag489-B16","doi-asserted-by":"crossref","DOI":"10.1016\/j.eclinm.2026.103874","article-title":"Metformin and epigenetic age in non-diabetic older people with HIV in Madrid (METFORAGING): a double-blind, randomised, placebo-controlled, pilot trial","volume":"95","author":"Marcelo-Calvo","year":"2026","journal-title":"eClinicalMedicine"},{"key":"2026081707364175500_ofag489-B17","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1097\/QAI.0000000000000983","article-title":"The effect of dolutegravir on the pharmacokinetics of metformin in healthy subjects","volume":"72","author":"Song","year":"2016","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2026081707364175500_ofag489-B18","doi-asserted-by":"crossref","first-page":"280","DOI":"10.2337\/dc16-1682","article-title":"Growth differentiation factor 15 as a novel biomarker for metformin","volume":"40","author":"Gerstein","year":"2017","journal-title":"Diabetes Care"},{"key":"2026081707364175500_ofag489-B19","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofaa338","article-title":"Repurposing metformin in nondiabetic people with HIV: influence on weight and gut microbiota","volume":"7","author":"Isnard","year":"2020","journal-title":"Open Forum Infect Dis"},{"key":"2026081707364175500_ofag489-B20","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/s41586-019-1911-y","article-title":"Gdf15 mediates the effects of metformin on body weight and energy balance","volume":"578","author":"Coll","year":"2020","journal-title":"Nature"},{"key":"2026081707364175500_ofag489-B21","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2021.103270","article-title":"LILAC pilot study: effects of metformin on mTOR activation and HIV reservoir persistence during antiretroviral therapy","volume":"65","author":"Planas","year":"2021","journal-title":"EBioMedicine"},{"key":"2026081707364175500_ofag489-B22","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1097\/QAD.0000000000003947","article-title":"Mavmet trial: maraviroc and\/or metformin for metabolic dysfunction associated fatty liver disease in adults with suppressed HIV","volume":"38","author":"McCabe","year":"2024","journal-title":"AIDS"}],"container-title":["Open Forum Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ofid\/advance-article-pdf\/doi\/10.1093\/ofid\/ofag489\/70499564\/ofag489.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/advance-article-pdf\/doi\/10.1093\/ofid\/ofag489\/70499564\/ofag489.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/advance-article-pdf\/doi\/10.1093\/ofid\/ofag489\/70499564\/ofag489.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:36:53Z","timestamp":1786966613000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ofid\/article\/doi\/10.1093\/ofid\/ofag489\/8752830"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,1]]},"references-count":22,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ofid\/ofag489","relation":{},"ISSN":["2328-8957"],"issn-type":[{"value":"2328-8957","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,8]]},"published":{"date-parts":[[2026,8,1]]},"article-number":"ofag489"}}