Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Year in Review
  • Published:

Obesity therapeutics in 2023

Advances in incretin-based therapeutics for obesity

Nature Reviews Endocrinology volume 20, pages 67–68 (2024)Cite this article

Subjects

The year 2023 brought reports of highly effective glucagon-like peptide 1 (GLP1) mono-agonists or combinations with amylin receptor agonists. Results for monomolecular co-agonists that added glucagon receptor and/or glucose-dependent insulinotropic polypeptide (GIP) receptor agonism to GLP1 receptor activation were also published in 2023. Interestingly, antagonistic GIP receptor antibodies conjugated with a GLP1 agonist were also shown to be effective.

Key advances

  • Of particular interest are the SURMOUNT trials from 2023 of the GLP1–GIP co-agonist tirzepatide, which have shown weight loss of up to 25% of body weight in people with obesity4.

  • A phase II trial with retatrutide, a GIP–GLP1–glucagon triple agonist, resulted in weight loss of 25% in patients with obesity3.

  • A new long-acting amylin-based agonist, cagrilintide, has shown good efficacy in obesity, especially in combination with the highly effective GLP1 receptor agonist semaglutide, with potential for weight loss exceeding 20%5.

  • Promising results of a small-molecule GLP1 receptor agonist (orforglipron)10 suggest that an orally active, effective agent will soon be made available, which is of huge interest in countries where injectable therapies are not immediately acceptable; positive results have also been reported for oral semaglutide2.

  • AMG 133 combines GLP1 agonism with GIP antagonism, and has shown promising results7.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Lincoff, A. M. et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2307563 (2023).

    Article  PubMed  Google Scholar 

  2. Knop, F. K. et al. Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 402, 705–719 (2023).

    Article  CAS  PubMed  Google Scholar 

  3. Jastreboff, A. M. et al. Triple-hormone-receptor agonist retatrutide for obesity - a phase 2 trial. N. Engl. J. Med. 389, 514–526 (2023).

    Article  CAS  PubMed  Google Scholar 

  4. Wadden, T. A. et al. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nat. Med. 29, 2909–2918 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Frias, J. P. et al. Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Lancet 402, 720–730 (2023).

    Article  CAS  PubMed  Google Scholar 

  6. Kizilkaya, H. S. et al. Loss of function glucose-dependent insulinotropic polypeptide receptor variants are associated with alterations in BMI, bone strength and cardiovascular outcomes. Front. Cell Dev. Biol. 9, 749607 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Strande, J. L. et al. A phase 1, randomized, double-blind, placebo-controlled single and multipleascending dose study of AMG 133 in subjects with obesity. Metabolism 142 (Suppl.), 155433 (2023).

    Article  Google Scholar 

  8. Killion, E. A. et al. Chronic glucose-dependent insulinotropic polypeptide receptor (GIPR) agonism desensitizes adipocyte GIPR activity mimicking functional GIPR antagonism. Nat. Commun. 11, 4981 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Willard, F. S. et al. Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist. JCI Insight 5, e140532 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Wharton, S. et al. Daily Oral GLP-1 receptor agonist orforglipron for adults with obesity. N. Engl. J. Med. 389, 877–888 (2023).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Mette M. Rosenkilde

Authors
  1. Mette M. Rosenkilde
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mette M. Rosenkilde.

Ethics declarations

Competing interests

M.M.R. is co-founder of Antag Therapeutics, Bainan Biotech and Synklino and serves as a board member of Bainan Biotech and Synklino.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rosenkilde, M.M. Advances in incretin-based therapeutics for obesity. Nat Rev Endocrinol 20, 67–68 (2024). https://doi.org/10.1038/s41574-023-00938-w

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41574-023-00938-w

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing