{"doi":"10.1038/s41591-025-03556-3","title":"Anti-obesity medication for weight loss in early nonresponders to behavioral treatment: a randomized controlled trial","abstract":"Current guidelines recommend behavioral treatment (BT) as the first intervention for patients with obesity. However, a substantial minority (35–50%) do not achieve a clinically meaningful loss of ≥5%. Anti-obesity medications (AOMs) are recommended when target weight loss is not achieved; however, their efficacy among BT nonresponders has not been established. This double-blind, randomized controlled proof-of-principle study evaluated whether augmenting BT with AOM improved 24-week weight loss compared to BT with placebo in early nonresponders to BT. A total of 147 adults with a body mass index ≥31 kg m−2 (≥28 kg m−2 with obesity-related comorbidity) completed an initial 4-week BT run-in. The 76 early nonresponders who lost <2.0% of initial weight were then randomized to 24 weeks of either BT plus placebo (BT + P, n = 38) or BT plus AOM (phentermine = 15.0 mg d−1, n = 38). Early responders received ongoing BT and were not part of the randomized trial. The primary outcome was met; early nonresponders assigned to BT + AOM had a greater mean (±s.e.) reduction in weight of 5.9 ± 0.7% from randomization to week 24, as compared to 2.8 ± 0.7% for those assigned to BT + P (mean difference = 3.1 ± 1.0, 95% confidence interval = 1.1–5.1%, Cohen’s d = 0.73, P = 0.003). Stepping up early BT nonresponders to BT + AOM improves their 24-week weight loss. ClinicalTrials.gov registration: NCT03779048 . A randomized clinical trial showing the superiority of behavioral treatment plus phentermine to behavioral treatment plus placebo for weight loss in those that previously had not responded to behavioral treatment.","journal":"Nature Medicine","year":2025,"id":513716,"datarank":0.3716272805136448,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.02623951656453785,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.02623951656453785,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":9,"citers_with_citation_signal":5,"citers_with_endowment":5,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03779048"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1376199,"name":"Eleanor Ghanbari","orcid":null,"position":1,"is_corresponding":false},{"id":325236,"name":"Jonathan D Chevinsky","orcid":"0000-0002-4535-8108","position":2,"is_corresponding":false},{"id":909276,"name":"Erica M. LaFata","orcid":"0000-0002-8505-6366","position":3,"is_corresponding":false},{"id":1375502,"name":"Alyssa M. Minnick","orcid":"0000-0001-7699-0184","position":4,"is_corresponding":false},{"id":1375503,"name":"Simran Rajpal","orcid":"0000-0001-9756-7510","position":5,"is_corresponding":false},{"id":1375504,"name":"Seamus Y Wang","orcid":"0000-0002-7529-6147","position":6,"is_corresponding":false},{"id":1376200,"name":"Kylie Burcaw","orcid":null,"position":7,"is_corresponding":false},{"id":304093,"name":"Robert I. Berkowitz","orcid":"0000-0002-5877-8195","position":8,"is_corresponding":false},{"id":110110,"name":"Thomas A. Wadden","orcid":"0000-0002-0438-4609","position":9,"is_corresponding":false},{"id":110111,"name":"Jena Shaw Tronieri","orcid":"0000-0003-3587-4130","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-19T02:48:23.284782Z","pmid":"40055520","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}