Clinical outcomes associated with drugs for obesity and overweight: A systematic review and network meta‐analysis of randomized controlled trials
Open accessAbstract
Aim: To compare the benefits and harms of drugs approved for weight management in adults with obesity or overweight. Materials and Methods: We performed a systematic review of drugs approved for treating obesity and overweight. We searched MEDLINE, Embase and CENTRAL through 26 February 2023. Random‐effects network meta‐analysis was applied. Results: A total of 168 trials (97 938 patients) were included. There was no evidence that drugs approved for weight management had different associations with cardiovascular death (69 trials, 59 037 participants). Naltrexone/bupropion was associated with lower cardiovascular mortality than placebo (odds ratio [OR], 0.62 [95% CI: 0.39, 0.99]; low certainty evidence). All drugs were associated with greater weight loss at 12 months than placebo (33 trials, 37 616 participants), mainly semaglutide (mean difference [MD], −9.02 kg [95% CI: −10.42, −7.63]; moderate certainty) and phentermine/topiramate (MD, −8.10 kg [95% CI: −10.14, −6.05]; high certainty); and with greater waist circumference reduction at 12 months than placebo (24 trials, 35 733 participants), mainly semaglutide (MD, −7.84 cm [95% CI: −9.34, −6.34]; moderate certainty) and phentermine/topiramate (MD, −6.20 cm [95% CI: −7.46, −4.94]; high certainty). Semaglutide and phentermine/topiramate were associated with lower or no difference in the odds of treatment withdrawal compared with all other drugs (87 trials, 70 860 participants). Conclusions: Among adults with obesity or overweight, semaglutide and phentermine/topiramate were associated with greater body weight loss and waist circumference reduction at 12 months than all other drugs, and lower or no significant difference in risks of withdrawal. There was no evidence that drugs approved for weight management had different associations with cardiovascular death.
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Incretin hormone-based drugs, first and foremost GLP-1RA, have emerged as a pivotal treatment option for managing both obesity and type 2 diabetes.
“Among these, incretin hormone‐based drugs, first and foremost glucagon‐like peptide 1 receptor agonists (GLP‐1RA), 11 have emerged as a pivotal treatment option for managing both obesity and T2D. 12 , 13 , 14 , 15”
Previous NMAs and a traditional meta-analysis on therapeutic options for overweight and obesity did not include more recently available OMMs such as tirzepatide, or included medications not approved for overweight/obesity, or adopted different inclusion criteria.
“Several NMAs20–23 and a traditional meta-analysis24 on different therapeutic options for overweight and obesity were published in the last few years, but they did not include more recently available OMMs, such as tirzepatide20–22, or they included medications not approved for the treatment of overweight/obesity (for example, metformin, SGLT2 inhibitors or GLP-1 agonists, such as dulaglutide)22, or”
From A systematic review and meta-analysis of the efficacy and safety of pharmacological treatments for obesity in adults (2025) · cites this paper as [21]
The results of this NMA are in line with those reported in previous NMA and meta-analysis.
“These results are in line with those reported in previous NMA and meta-analysis20–22,24”
From A systematic review and meta-analysis of the efficacy and safety of pharmacological treatments for obesity in adults (2025) · cites this paper as [21]
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Tirzepatide Once Weekly for the Treatment of Obesity
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Graphical tools for network meta-analysis in STATA
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CINeMA: an approach for assessing confidence in the results of a network meta-analysis
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“Frequentist network meta-analysis was then performed to compare available treatment strategies within a single analytical framework.(19,20) For each network, the extent of heterogeneity was assessed using the maximum likelihood method.”
MethodEvaluating the quality of evidence from a network meta-analysis
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“The ongoing SELECT trial will further elucidate whether these benefits will translate into a reduction in major cardiovascular events.(31) The strength of this systematic review includes the comparison of approved pharmacological approaches for weight management in adults with obesity or overweight.”
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Incretin-based therapies for the treatment of obesity-related diseases
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Self-citation
- Authors
- Iannone, A., Natale, P., Palmer, S. C., Nicolucci, A., Rendina, M., Giorgino, F., Laviola, L., Di Leo, A., & Strippoli, G. F. M.
- Affiliations
- University of Bari Aldo Moro (IT)
- University of Foggia (IT)
- University of Otago (NZ)
- Center for Outcomes Research and Clinical Epidemiology (IT)
- Section of Gastroenterology, Department of Emergency and Organ Transplantation University of Bari Bari Italy
- The University of Sydney (AU)
- Corresponding author
- Iannone, Andrea
- ORCID
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2023-05-31
- Volume
- 25
- Issue
- 9
- Pages
- 2535-2544
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W4378782117
- Cited by
- 27
- References
- 11
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 8 · 2023: 2
- FWCI
- 0.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Obesity and Metabolism (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Funders
- University of Sydney
- Topics
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Obesity, Physical Activity, Diet
- Keywords
- obesity, overweight, anti-obesity drugs, semaglutide, phentermine/topiramate, naltrexone/bupropion, cardiovascular mortality, weight loss, waist circumference, treatment withdrawal, drug safety
- MeSH terms
- Network Meta-Analysis, Topiramate, Adult, Humans, Obesity, Phentermine, Randomized Controlled Trials as Topic, Overweight
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