Novel therapeutic targets in the treatment of obesity: a review

Authors

  • Zainab Hafedh Alsharifi
  • Aymen A. Bash

DOI:

https://doi.org/10.60988/p.v37i2S.270

Keywords:

obesity; ghrelin; gut peptides; weight loss; appetite

Abstract

Obesity is a chronic condition that increases the risk of both complications and mortality. The development of effective and safe entero-pancreatic peptide-based pharmacotherapies (such as those targeting ghrelin, leptin, peptide YY, and related molecules) requires a nuanced understanding of the gut–brain axis and its role in regulating appetite and body weight. This brief review places particular emphasis on novel incretin-based agents co-formulated with glucagon and neuropeptide Y, which have demonstrated weight-reduction outcomes approaching those of bariatric surgery, yet without the invasiveness of surgical intervention. In cases where obesity-related comorbidities (such as type 2 diabetes mellitus) are present, such substantial weight loss may contribute to clinical improvement, especially given that many of these agents exert independent effects on glycaemic control. Additionally, we herein evaluate the therapeutic potential of ghrelin inhibition via ghrelin-O-acyltransferase blockade, concluding that this approach does not yield meaningful effects on satiety, body weight, or caloric intake. Finally, we discuss emerging compounds currently under clinical investigation that may offer future avenues for obesity treatment.

Author Biographies

Zainab Hafedh Alsharifi

College of Pharmacy, University of Babylon, Hillah, Iraq

Aymen A. Bash

Department of Pharmacology, College of Pharmacy, University of Babylon, Hillah, Iraq

References

1. Papamargaritis D., le Roux C.W., Holst J.J., Davies M.J. New therapies for obesity. Cardiovasc. Res. 119(18), 2825–2842, 2024. DOI: 10.1093/cvr/cvac176

1. Rubinić I., Kurtov M., Likić R. Novel pharmaceuticals in appetite regulation: exploring emerging gut peptides and their pharmacological prospects. Pharmacol. Res. Perspect. 12(4), e1243, 2024. DOI: 10.1002/prp2.1243

2. Haddawi K.H., Al-Ziaydi A.G., Al-Kathem Al-Khalidi F.A. The role of adipokines and ghrelin in interactions and clinical implications in childhood obesity. J. Educ. Health Promot. 13, 40, 2024. DOI: 10.4103/jehp.jehp_972_23

3. Bianzano S., Henrich A., Herich L., Kalsch B., Sarubbi D., Seitz F., et al. Efficacy and safety of the ghrelin-O-acyltransferase inhibitor BI 1356225 in overweight/obesity: data from two Phase I, randomised, placebo-controlled studies. Metabolism 143, 155550, 2023. DOI: 10.1016/j.metabol.2023.155550

4. Nicze M., Dec A., Borówka M., Krzyżak D., Bołdys A., Bułdak Ł., et al. Molecular mechanisms behind obesity and their potential exploitation in current and future therapy. Int. J. Mol. Sci. 25(15), 8202, 2024. DOI: 10.3390/ijms25158202

5. Melson E., Ashraf U., Papamargaritis D., Davies M.J. What is the pipeline for future medications for obesity? Int. J. Obes. (Lond.) 49(3), 433–451, 2025. DOI: 10.1038/s41366-024-01473-y

6. Gewitz A., Mendell J., Wang Y., Harris C., Olenchock B.A., Podgrabinska S., et al. Pharmacokinetics and pharmacodynamics of mibavademab (a leptin receptor agonist): results from a first-in-human phase I study. Clin. Transl. Sci. 17(4), e13762, 2024. DOI: 10.1111/cts.13762

7. Christoffersen B.Ø., Skyggebjerg R.B., Bugge A., Kirk R.K., Vestergaard B., Uldam H.K., et al. Long-acting CCK analogue NN9056 lowers food intake and body weight in obese Göttingen Minipigs. Int. J. Obes. (Lond.) 44(2), 447–456, 2020. DOI: 10.1038/s41366-019-0386-0

8. Tuğal Aslan D., Göktaş Z. The therapeutic potential of theobromine in obesity: a comprehensive review. Nutr. Rev. 83(5), 859–868, 2025. DOI: 10.1093/nutrit/nuae122

9. Hope D.C.D., Hinds C.E., Lopes T., Vincent M.L., Shrewsbury J.V., Yu A.T.C., et al. Hypoaminoacidemia underpins glucagon-mediated energy expenditure and weight loss. Cell Rep. Med. 3(11), 100810, 2022. DOI: 10.1016/j.xcrm.2022.100810

Downloads

Published

10-10-2025

How to Cite

[1]
Alsharifi, Z.H. and Bash, A.A. 2025. Novel therapeutic targets in the treatment of obesity: a review. Pharmakeftiki . 37, 2S (Oct. 2025). DOI:https://doi.org/10.60988/p.v37i2S.270.