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Review
. 2025 Feb 12;17(2):238.
doi: 10.3390/pharmaceutics17020238.

Advances in Oral Biomacromolecule Therapies for Metabolic Diseases

Qiuxia Jiao  1 , Yuan Huang  2 , Jinhan He  1   2 , Yining Xu  1   2
Affiliations
Review

Advances in Oral Biomacromolecule Therapies for Metabolic Diseases

Qiuxia Jiao et al. Pharmaceutics. .

Abstract

Metabolic diseases like obesity and diabetes are on the rise, and therapies with biomacromolecules (such as proteins, peptides, antibodies, and oligonucleotides) play a crucial role in their treatment. However, these drugs are traditionally injected. For patients with chronic diseases (e.g., metabolic diseases), long-term injections are accompanied by inconvenience and low compliance. Oral administration is preferred, but the delivery of biomacromolecules is challenging due to gastrointestinal barriers. In this article, we introduce the available biomacromolecule drugs for the treatment of metabolic diseases. The gastrointestinal barriers to oral drug delivery and strategies to overcome these barriers are also explored. We then discuss strategies for alleviating metabolic defects, including glucose metabolism, lipid metabolism, and energy metabolism, with oral biomacromolecules such as insulin, glucagon-like peptide-1 receptor agonists, proprotein convertase subtilisin/kexin type 9 inhibitors, fibroblast growth factor 21 analogues, and peptide YY analogues.

Keywords: gastrointestinal tract; metabolic diseases; oral biomacromolecules; oral drug delivery.

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Conflict of interest statement

The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
Barriers and strategies for oral delivery of biomacromolecules. Note: the strategies are not strictly region-specific. Created with Biorender.com.
Figure 2
Figure 2
Intelligent microrobot pill delivery systems used for oral insulin against hyperglycemia. (A) The microjet delivery (MiDe) systems. (B) The luminal unfolding microneedle injection (LUMI) device. (C) The magneto-responsive microneedle robots (MMRs). (D) The cylindrical needle-covered pill. (E) The robotic mucus-clearing capsule (RoboCap). (F) The self-unfolding proximity enabling devices (SPEDs). Adapted and reproduced with permission from ref. [135,227,255,261,262,263,264].
Figure 3
Figure 3
Pharmacokinetic (PK) and pharmacodynamic (PD) evaluations of AZD8233 tablets in dogs and cynomolgus monkeys and predicted PKPD parameters in humans. (A) The area under curve (AUC) of repeated daily oral administrations of AZD8233 tablets in dogs. (B) The inhibition percentage of PCSK9 and LDL cholesterol in healthy cynomolgus monkeys after AZD8233 administrations by the oral and subcutaneous routes, respectively. (C) Predicted PKPD parameters of AZD8233 in humans by daily oral administration versus monthly subcutaneous administration. Adapted and reproduced with permission from ref. [287].
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References

    1. Neeland I.J., Lim S., Tchernof A., Gastaldelli A., Rangaswami J., Ndumele C.E., Powell-Wiley T.M., Després J.P. Metabolic syndrome. Nat. Rev. Dis. Primers. 2024;10:77. doi: 10.1038/s41572-024-00563-5. - DOI - PubMed
    1. Silveira Rossi J.L., Barbalho S.M., Reverete de Araujo R., Bechara M.D., Sloan K.P., Sloan L.A. Metabolic syndrome and cardiovascular diseases: Going beyond traditional risk factors. Diabetes Metab. Res. Rev. 2022;38:e3502. doi: 10.1002/dmrr.3502. - DOI - PubMed
    1. Stasi A., Cosola C., Caggiano G., Cimmarusti M.T., Palieri R., Acquaviva P.M., Rana G., Gesualdo L. Obesity-Related Chronic Kidney Disease: Principal Mechanisms and New Approaches in Nutritional Management. Front. Nutr. 2022;9:925619. doi: 10.3389/fnut.2022.925619. - DOI - PMC - PubMed
    1. Fahed G., Aoun L., Bou Zerdan M., Allam S., Bou Zerdan M., Bouferraa Y., Assi H.I. Metabolic Syndrome: Updates on Pathophysiology and Management in 2021. Int. J. Mol. Sci. 2022;23:786. doi: 10.3390/ijms23020786. - DOI - PMC - PubMed
    1. Chew N.W.S., Ng C.H., Tan D.J.H., Kong G., Lin C., Chin Y.H., Lim W.H., Huang D.Q., Quek J., Fu C.E., et al. The global burden of metabolic disease: Data from 2000 to 2019. Cell Metab. 2023;35:414–428.e413. doi: 10.1016/j.cmet.2023.02.003. - DOI - PubMed

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