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Benefit-Risk Assessment of Obesity Drugs: Focus on Glucagon-like Peptide-1 Receptor Agonists

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A Correction to this article was published on 30 April 2019

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Abstract

The prevalence of obesity and related comorbidities is increasing worldwide. Furthermore, clinically meaningful body weight losses has proven difficult to achieve and especially to maintain through sustained lifestyle change in the form of diet and exercise. Pharmacotherapy against obesity is a non-invasive treatment as an adjunct to lifestyle changes, but approved anti-obesity drugs are currently few. This article reviews the major anti-obesity drugs and the benefit-risk profiles of the long-acting glucagon-like peptide-1 receptor agonists (GLP-1 RAs) liraglutide and semaglutide (a modified version of liraglutide with longer half-life and tripled receptor affinity). Generally, GLP-1 RAs are well tolerated and induce significant weight loss and lowering of comorbidities. Studies with liraglutide 3.0 mg/day have shown an average placebo-subtracted weight loss of 5.5 kg (range 4.6–5.9) in 1- to 3-year duration trials. One trial using semaglutide 0.4 mg once daily reported an average weight loss of 11.6% (~ 13.1 kg) after 1 year. Furthermore, semaglutide induced a ~ 6 percentage point larger placebo-subtracted body weight loss in a head-to-head comparison with liraglutide (11.6 vs. 5.5% weight loss, respectively). The safety profiles for both drugs were similar, with transient gastrointestinal disorders being the most commonly reported adverse events. The longest running trial and the most recent trials have not raised any new safety concerns. Long-term trials and post-marketing surveillance is warranted to fully assess both long-term efficacy and safety. Future combinational therapies of mimicked gut hormones involved in regulation of energy homeostasis and/or additional lifestyle change in the form of exercise might further improve efficacy.

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Change history

  • 30 April 2019

    In the original publication of this article, the following correction should be noted in Table 1.

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Authors and Affiliations

  1. Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, Denmark

    Rasmus M. Christensen, Christian R. Juhl & Signe S. Torekov

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  1. Rasmus M. Christensen
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Contributions

Conceptualisation and methodology: SST. Writing first draft: RMC. Critically editing, re-writing, analysing and reviewing the manuscript: SST, RMC, and CRJ.

Corresponding author

Correspondence to Signe S. Torekov.

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Funding

This work was supported by the Tripartite Immunometabolism Consortium [TrIC], Novo Nordisk Foundation; grant number NNF15CC0018486.

Conflict of interest

Rasmus Michael Christensen was supported by the Novo Nordisk Foundation, grant number NNF15CC0018486. Christian Rimer Juhl has no conflicts of interest that are directly relevant to the content of this article. Signe Sørensen Torekov has received research grants from the Novo Nordisk Foundation and Novo Nordisk A/S.

Additional information

The original version of this article was revised: The drug “Orlistat” was incorrectly changed to “Gastrointestinal lipase inhibitor” in Table 1 and the same has been corrected.

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Christensen, R.M., Juhl, C.R. & Torekov, S.S. Benefit-Risk Assessment of Obesity Drugs: Focus on Glucagon-like Peptide-1 Receptor Agonists. Drug Saf 42, 957–971 (2019). https://doi.org/10.1007/s40264-019-00812-7

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