Pretoria, 11 November 2025 – The South African Health Products Regulatory Authority (SAHPRA) cautions members of the public against purchasing or using GLP-1 (glucagon-like peptide-1) products that are being promoted and sold on various social media platforms. These products are being promoted to assist with weight loss.

SAHPRA has become aware of companies and individuals illegally marketing GLP-1 products online and falsely claiming to be affiliated with or authorised by SAHPRA and some of South Africa’s major retail pharmacies. The Authority wishes to clarify that these claims are untrue.

SAHPRA, through its investigation, has discovered that the sellers of these products are not based in South Africa. The products are being shipped from China via post offices, not from a warehouse in Johannesburg or Cape Town, as stated in the advertisements. The shipped products are not identical to the advertised products.  SAHPRA has not approved any oral GLP-1 solution for consumption.

A picture of these products, displaying SAHPRA’s logo and claiming to be approved by SAHPRA, can be seen below.

SAHPRA urges the public to exercise caution when they are buying medicines online, from unknown websites or social media pages, as these medicines may contain dangerous/harmful ingredients that might not be disclosed to the patients by the seller. Patients should only buy prescribed medicines from licensed and reputable pharmacies. A list of medicines registered in South Africa can be found on the SAHPRA website.

SAHPRA further warns that the unauthorised selling, distribution, or advertising of medicines not registered with SAHPRA is a contravention of the Medicines and Related Substances Act, 1965 (Act 101 of 1965), as amended. The Authority shall take all the necessary regulatory and legal action against any individual or organisation found engaging in such practices.

Members of the public are urged to report any suspicious medicine sales or false claims of SAHPRA approval. You can report through these whistleblower platforms, SAHPRA’s 24-hour hotline (0800 204 307) or via our web reporting facility: https://bit.ly/3nrku5t

“Safeguarding the well-being of the South African public remains a primary concern for the regulatory authority. SAHPRA is monitoring the supply chain as well as the online platforms for unregistered, substandard, and falsified medicines containing or claiming to contain GLP-1 Substances,” indicated SAHPRA CEO, Dr Boitumelo Semete-Makokotlela.

Read more here : https://www.sahpra.org.za/news-and-updates/sahpra-warns-the-public-about-glp-1-products-sold-through-social-media-platforms/

However, the expanding potential of peptide-based therapeutics highlights distinct challenges for their development. Advances in stability, delivery and safety assessment are reshaping capabilities, while evolving frameworks for nonclinical studies and development programmes provide a clearer roadmap for success.

Therapeutic value and clinical progress

Peptides can be categorised into several classes, including natural peptides (that occur naturally in the body), synthetic peptides (made synthetically in the lab), macrocyclic peptides (whose structure makes them behave differently than other peptides) and disulfide-rich versions (stabilising disulfide chemical bonds). These molecules can be especially useful in treating complex diseases due to their ability to mimic endogenous ligands – the body’s own signalling chemicals – and connect with a wide range of targets, especially G protein-coupled receptors (GPCRs), which help control many bodily functions.

Between 2004 and 2017, 46 peptide‑based drugs received regulatory approval, underscoring significant clinical momentum. More recently, the peptide landscape has continued to expand. By mid‑2024, over 110 peptide‑based therapeutics had been approved worldwide, including noteworthy high-profile GLP-1 receptor agonists such as semaglutide and tirzepatide.¹ Their high target specificity and often favourable safety profiles combine with structural flexibility, enabling a broad range of chemical modifications that further reinforce peptides’ potential for treating a wide variety of complex diseases.

Challenges in development: stability, delivery and immunogenicity

Despite their promise, peptide therapeutics pose distinct challenges in the development process, especially concerning stability, delivery and immunogenicity.

Peptides are inherently susceptible to enzymatic degradation within the body, making them difficult to deliver orally and limiting their duration of activity in the bloodstream. While these issues have made it challenging to develop and use peptide drugs effectively in the past,²advances in formulation science have established strategies to improve their pharmacokinetic properties. Attaching stabilising molecules (PEGylation), forming ring-shaped structures (cyclisation), adding fat-like groups (lipidation) and using advanced delivery systems have helped peptides last longer in the body and work more effectively.

Immunogenicity, however, continues to present a distinct challenge. In both laboratory and clinical settings, many peptide-based therapies have been shown to trigger the body’s immune system to produce anti-drug antibodies (ADAs). While this response is quite common, it rarely affects how the drug behaves in the body: more than 90 percent of clinical cases with ADA presence showed no meaningful impact on the drug’s pharmacokinetics (PK) or pharmacodynamics (PD).³ Predicting this immune response early on, however, is difficult. Factors like peptide chain length or the incorporation of non-proteinogenic amino acids don’t consistently indicate the likelihood of an immune reaction, which complicates the early risk assessments needed to develop safe and effective studies.

Toxicological considerations and nonclinical study design

A robust nonclinical safety assessment is pivotal to overcome these challenges and derisk peptide drug development. It is also critical that each element of the process is aligned with current International Council for Harmonisation (ICH) guidelines tailored to the unique features of peptide therapeutics, including M3(R2), S6(R1), S9 and S7 series documents.

Core safety studies

To ensure the safety of new peptide drugs before clinical applications, scientists must perform a robust programme of nonclinical studies. These tests reveal how drugs behave in the body and the potential risks they may pose. The core tests include:

• Repeated-dose toxicity studies – these show what happens when the drug is given repeatedly over time, helping to identify any harmful effects that build up
• Toxicokinetic studies – these measure how the drug is absorbed, distributed, broken down and cleared from the body
• Safety pharmacology studies – these examine how drugs affect critical systems like the central nervous, cardiovascular and respiratory systems
• Genetic toxicology studies – these check whether the drug might damage DNA and increase the risk of cancer.

Depending on the drug’s intended administration and target, additional studies may be needed. These can include tests for phototoxicity, local toxicity and reproductive toxicity. Designing and conducting the right combination of tests provides a more thorough understanding of the drug’s safety profile. A comprehensive approach helps protect future patients and supports regulatory approval.

In vivo species selection

Species selection for nonclinical in vivo studies is particularly important. Nonclinical study design should prioritise models with metabolic profiles and target engagement characteristics that closely resemble those of humans to ensure translational relevance and regulatory alignment. For example, the safety evaluation of semaglutide encompassed repeated-dose studies across multiple nonclinical models of varying durations, supplemented by comprehensive safety pharmacology and genotoxicity assessments.

Genotoxicity considerations

When evaluating the genetic safety of peptide drugs, it is important to consider the peptide’s cellular uptake and chemical composition. Peptides with cell-permeating properties or those with non-natural amino acids may warrant additional in vitro and in vivo genotoxicity testing. A step-by-step approach is the best course of action, starting with evaluating known moieties, pharmacological relevance and potential DNA interactions.

A final word

Peptides are positioned to play a central role in addressing diseases with high unmet need for treatment. However, their development demands nuanced approaches, including optimised nonclinical testing strategies to reflect their unique biochemical and pharmacological properties.

Incorporating the latest advancements in programme design with a nuanced understanding of peptide-specific challenges can unlock broader clinical potential across a wide range of therapeutic areas. Collaborating with a laboratory partner experienced in peptide characterisation and translational study design further enhances programme efficiency, mitigates risk and supports the rigorous standards required for successful development.

References:

1. Elsayed YY, Kühl T, Imhof D. (2025). Regulatory Guidelines for the Analysis of Therapeutic Peptides and Proteins. Journal of Peptide Science, 31(3), e70001. https://doi.org/10.1002/psc.70001
2. Baral KC, Choi KY. (2025). Barriers and Strategies for Oral Peptide and Protein Therapeutics Delivery: Update on Clinical Advances. Pharmaceutics, 17(4), 397. https://doi.org/10.3390/pharmaceutics17040397
3. Shankar, et al. (2014). Assessment and Reporting of the Clinical Immunogenicity of Therapeutic Proteins and Peptides—Harmonized Terminology and Tactical Recommendations. The AAPS Journal, 16(4), 658. https://doi.org/10.1208/s12248-014-9599-2

The past few years have seen a boom in the market for protein- and peptide-based drugs, with the global market for peptide-based drugs expected to reach approximately $80 billion by 2032.¹ The primary reason is that peptide-based drugs can be highly effective,² leading to fewer off-target interactions and excellent biocompatibility. However, some of the major issues with these potentially game-changing therapeutic agents include their short lifespan within the body (they are prone to hydrolysis and enzymatic degradation) and their poor oral bioavailability, which is often between 1 and 2 percent.

To date, this poor oral bioavailability² has meant that peptides have been administered parenterally (ie, via intravenous injection). Not only has the technology for successful oral administration been unavailable, but the medical need outweighed the drawbacks of regular injections; notably the peptide insulin³ has saved tens of millions of lives over the last 100 years, despite its delivery requiring injection. However, recent advances in the development of peptide-based drugs have led to improvements in peptide solubility and oral bioavailability for both linear and cyclic peptides, with several drugs being approved or entering clinical trials. For example, orally bioavailable PCSK9 inhibitor, Enlicitide (MK-0616), is currently in Phase III trials for treatment of adult hypercholesterolemia. Similarly, Icotrokinra (JNJ-2113),⁴ an orally administered peptide-based treatment for psoriasis, is currently also in Phase III trials.

Strategies for oral bioavailability of peptides

There are several strategies for improving oral bioavailability of peptides that are largely aimed at chemically altering the amino acids in the chain, causing cyclisation which aids delivery of the peptide to the site of interest. In addition, formulation strategies have also been explored for improving the oral bioavailability of peptides.

Altering peptides at the amino-acid level

While the strategies for optimisation of small molecules are well established, such as adjusting lipophilicity, installation of (bio)isosteres and using prodrugs, similar strategies for use in peptides are far less developed. However, significant work has taken place in this area, which is now levelling the playing field.

Peptide sequences can be tailored through chemical modifications that impact their in vivo behaviour and physicochemical properties. In particular, the improvement of therapeutic half-life⁵ through incorporation of non-natural amino acids, D-amino acids, PEGylation, N- and C-terminal modifications, and attachment on the side chains has afforded an extended therapeutic window of activity in vivo, leading to dosing regimens that are comparable to those of small molecules. Of these, modification of peptide sequences and attachment of lipids to enhance binding to albumin⁶ or other proteins have proven effective strategies to improve peptide half-life.

Cyclic peptides

Cyclic peptides are receiving increased attention⁷ and offer significant potential to address the challenges of peptide-based therapeutics. As with all peptides, when administered orally they are rapidly digested and/or have low absorption in the GI tract. However, these issues can sometimes be circumvented, for example through N-alkylation,⁸ inclusion of D-amino acids or use of disulfide, ring closing metathesis (RCM) or lactam formation as cyclisation approaches.⁷ In addition, the use of cyclic peptides in combination with some of the other outlined strategies for oral bioavailability paves the way for significant advances in drug discovery and development.

Nanoparticles

Nanoparticles (NPs) are defined as solid particles between one and 100nm in size that have colloidal properties when dispersed in an aqueous phase. It has consistently been shown that use of NPs can enhance solubility of poorly soluble compounds,⁹ including peptides,¹⁰ eg, through adjusting interaction with mucous barriers in the small intestine,¹¹ blocking enzyme metabolism or enabling colon-specific drug delivery. Many examples of NP-based peptide drugs are currently under investigation¹² for targeted delivery across the blood–brain barrier as well as in the treatment of breast cancer.

Permeation enhancers

Permeation enhancers (PEs) are designed to facilitate passage of the peptide through the skin or other barriers, thereby enhancing absorption of the drug. In the case of oral peptide medications, PEs are incorporated to alter the integrity of the intestinal epithelial barrier. These formulations often include medium-chain fatty acid-based systems, bile salts, acyl carnitines and the chelating agent EDTA.¹³  However, while these approaches can provide benefit in the treatment of indications, there are limitations: fasting is often required before and after drug administration (such as with the GLP-1 receptor agonist Rybelsus,¹⁴ which contains salcaprozate sodium (SNAC) as the PE) and some have raised safety concerns due to the potential for irreversible intestinal epithelium damage.¹³

Self-emulsifying drug delivery systems

Self-emulsifying drug delivery systems (SEDDS) comprise mixtures of lipids, surfactants and co-solvent that, when dispersed in gastrointestinal fluid, form emulsions and microemulsions. These can overcome barriers to absorption by providing protection from metabolism and improving penetration through the intestinal mucus layer. Currently cyclosporin A (Sandimmune/Neoral®)¹⁵ is formulated with SEDDS, which has an impressive bioavailability of 20–40 percent.

What does the future hold?

The field of peptide-based therapeutics is both old, with the first peptide-based drug (insulin) developed over 100 years ago, and young at the same time, with new modalities and classes of compounds continuously being developed. Due to the advances in bioavailability of peptides, peptide-based therapeutics are currently at the cusp of a revolution and will undoubtedly be an important modality for addressing unmet medical need and treatment of diseases in the future.

Peptides and Sai Life Sciences

Sai Life Sciences is a leader in the field of peptides and peptide-based therapeutics and is well-placed to support research and drug development efforts. With expertise in peptide synthesis, analysis, biological screening, ADME-PK characterization and storage, as well as formulation development, we can develop innovative medicines faster.

References

1. Rossino G, Marchese E, Galli G, et al. Peptides as Therapeutic Agents: Challenges and Opportunities in the Green Transition Era. Molecules, 28 (20), 7165-7203, 2023. https://doi.org/10.3390/molecules28207165
2. Chen G, Kang W, Li W, et al. Oral delivery of protein and peptide drugs: from non-specific formulation approaches to intestinal cell targeting strategies. Theranostics, 12 (3), 1419-1439, 2022. https://doi.org/10.7150/thno.61747
3. Levy M. Insulin Development and Commercialization, American Chemical Society. https://www.acs.org/education/whatischemistry/landmarks/insulin.html (Accessed March 2025).
4. Icotrokinra delivered an industry-leading combination of significant skin clearance with demonstrated tolerability in a once daily pill in Phase 3 topline results. Johnson & Johnson. https://www.jnj.com/media-center/press-releases/icotrokinra-delivered-an-industry-leading-combination-of-significant-skin-clearance-with-demonstrated-tolerability-in-a-once-daily-pill-in-phase-3-topline-results (Accessed March 2025).
5. Mathur D, Prakash S, Anand P, et al. PEPlife: A Repository of the Half-life of Peptides. Sci. Rep., 6, 36617, 2016. https://doi.org/10.1038/srep36617
6. Menacho-Melgar R, Decker JS, Hennigan JN, Lynch MD. A review of lipidation in the development of advanced protein and peptide therapeutics. J. Contr. Release., 295 (10), 1-12. https://doi.org/10.1016/j.jconrel.2018.12.032
7. Merz ML, Habeshian S, Li B, et al. De novo development of small cyclic peptides that are orally bioavailable. Nat. Chem. Biol., 20, 624-633, 2024. https://doi.org/10.1038/s41589-023-01496-y
8. Räder AFB, Reichart F, Weinmüller M, Kessler H. Improving oral bioavailability of cyclic peptides by N-methylation. Bioorg. Med. Chem., 26 (10), 2766-2773, 2018. https://doi.org/10.1016/j.bmc.2017.08.031
9. Cao S-J, Xu S, Wang H-M, et al. Nanoparticles: Oral Delivery for Protein and Peptide Drugs. AAPS PharmSciTech, 20, 190, 2019. https://doi.org/10.1208/s12249-019-1325-z
10. US Patent US9949924B2. Methods and compositions for oral administration of protein and peptide therapeutic agents. https://patents.google.com/patent/US9949924B2/en
11. Ruiz-Gatón L, Espuelas S, Larrañeta E, et al. Pegylated poly(anhydride) nanoparticles for oral delivery of docetaxel. Eur. J. Pharm. Sci., 118, 165-175, 2018. https://doi.org/10.1016/j.ejps.2018.03.028
12. Sharma R, Borah SJ, Bhawna, et al. Functionalized Peptide-Based Nanoparticles for Targeted Cancer Nanotherapeutics: A State-of-the-Art Review. ACS Omega, 7 (41), 36092–36107, 2022. https://doi.org/10.1021/acsomega.2c03974
13. McCartney F, Gleeson JP, Brayden DJ. Safety concerns over the use of intestinal permeation enhancers: A mini-review. Tissue Barriers, 4, 2, e1176822, 2016. https://doi.org/10.1080/21688370.2016.1176822
14. Semaglutide. Drugbank. https://go.drugbank.com/drugs/DB13928 (Accessed March 2025)
15. Cyclosprorine. Drugbank. https://go.drugbank.com/drugs/DB00091 (Accessed March 2025)