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Cited by 12Pharmacology and Obesity TreatmentObesity, Physical Activity, DietBariatric Surgery and Outcomes

Anti-obesity medication for weight loss in early nonresponders to behavioral treatment: a randomized controlled trial

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Tronieri, Jena S., Ghanbari, Eleanor, Chevinsky, Jonathan, LaFata, Erica M., Minnick, Alyssa M., Rajpal, Simran, Wang, Seamus Y., Burcaw, Kylie +2 more·2025·Nature Medicine
DOI 10.1038/s41591-025-03556-3PMC PMC12092266
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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.

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  • In a 2025 RCT, early non-responders to behavioral therapy who received phentermine 15 mg/day lost 3.1% more weight at 24 weeks than those continuing therapy with placebo (5.9% vs 2.8%; P = 0.003).

    “In a 2025 RCT, early non-responders to behavioral therapy who received phentermine 15 mg/day lost 3.1% more Weight at 24 weeks than those continuing therapy with placebo (5.9% vs. 2.8%; P = 0.003) [184].”

    From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [184]

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Research works printed but not linked: 21

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Cited by

Sorted by citations

Authors
Tronieri, J. S., Ghanbari, E., Chevinsky, J., LaFata, E. M., Minnick, A. M., Rajpal, S., Wang, S. Y., Burcaw, K., Berkowitz, R. I., & Wadden, T. A.
Affiliations
  • University of Pennsylvania (US)
  • Beth Israel Deaconess Medical Center (US)
  • Drexel University (US)
  • Children's Hospital of Philadelphia (US)
Corresponding author
Tronieri, Jena S.
ORCID
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2025-03-07
Volume
31
Issue
5
Pages
1653-1660
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/s41591-025-03556-3
PMC
PMC12092266
OpenAlex
W4408235325
Cited by
12
References
14
Citations by year
2026: 9 · 2025: 3
FWCI
6.79
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Medicine (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (K23DK116935)
Topics
  • Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Obesity, Physical Activity, Diet
  • Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
Keywords
anti-obesity drugs, phentermine, behavioral weight loss, obesity, treatment non-responders, body mass index
MeSH terms
Adult, Behavior Therapy, Double-Blind Method, Female, Humans, Male, Middle Aged, Obesity, Phentermine, Weight Loss, Body Mass Index, Treatment Outcome, Anti-Obesity Agents

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