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Bariatric Surgery

Association of long-term weight management pharmacotherapy with multiple health outcomes: an umbrella review and evidence map

International Journal of Obesity volume 49, pages 464–477 (2025)Cite this article

Subjects

Abstract

Background

Multiple meta-analyses (MAs) have demonstrated that six pharmacotherapies, including orlistat, liraglutide, phentermine/topiramate, naltrexone/bupropion, semaglutide, and tirzepatide, improve weight loss and weight maintenance. However, few studies have synthesized and evaluated the quality of this evidence.

Objective

To identify the relevant MAs of randomized clinical trials (RCTs) that explored the association between the six pharmacotherapies and obesity-related health outcomes and adverse events (AEs).

Methods

A comprehensive search was conducted across PubMed, Embase, Cochrane Library, and Web of Science from database inception up to January 2024. We calculated the effect size as the mean difference and risk ratio using the random-effects model. The quality of MAs was evaluated using “A Measurement Tool to Assess Systematic Reviews 2”.

Results

Sixteen MAs comprising 235 RCTs that described 115 unique associations between the six pharmacotherapies and various health outcomes were included. Overall, 101 statistically significant associations (88%) had beneficial outcomes on body weight, weight loss, waist circumference, body mass index, total cholesterol, triglycerides, both low-density and high-density lipoprotein cholesterol, blood pressure, and glycemic profile. The pharmacotherapies were associated with significant weight loss and partial improvements in the lipid profile, blood pressure, and glycemic control among individuals with overweight or obesity. Notable AEs were associated with liraglutide, naltrexone/bupropion, semaglutide, and orlistat. The methodological quality of the included MAs requires improvement.

Conclusions

This umbrella review identified significant beneficial associations between pharmacotherapies and anthropometric measures, lipid profile, blood pressure, glycemic profile, and quality-of-life outcomes in individuals with overweight or obesity. In addition, the umbrella review highlighted safety considerations. The findings affirm the efficacy of the six pharmacotherapies in promoting weight loss in this demographic. Further clinical trials with long-term follow-up are essential to evaluate the effects of these pharmacotherapies on clinical outcomes, including cancer, cardiovascular events, and mortality.

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Data availability

The data for this article can be found in the Appendix.

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Funding

This research was funded by the Gansu Provincial Youth Science and Technology Fund Program (No. 22JR5RA706), the 2022 Master/Doctor/Postdoctoral program of NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor (No. NHCDP2022017).

Author information

Author notes

  1. These authors contributed equally: Ting-ting Lu, Bin Liu.

Authors and Affiliations

  1. Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China

    Ting-ting Lu

  2. NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou, China

    Bin Liu

  3. Evidence-Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China

    Long Ge

  4. Center for Clinical Epidemiology and Evidence-Based Medicine, Beijing Children’s Hospital, Capital Medical University, Beijing, China

    Ya-li Liu

  5. Center for Optometry, Gansu Provincial Hospital, Lanzhou, China

    Yu Lu

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  1. Ting-ting Lu
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  5. Yu Lu
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Contributions

TTL and YL contributed to the conception and design. TTL and BL contributed to the acquisition of data. YLL and LG contributed to the analysis and interpretation of data; TTL and BL drafted the manuscript; YL revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Ting-ting Lu or Yu Lu.

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Lu, Tt., Liu, B., Ge, L. et al. Association of long-term weight management pharmacotherapy with multiple health outcomes: an umbrella review and evidence map. Int J Obes 49, 464–477 (2025). https://doi.org/10.1038/s41366-025-01719-3

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