What does it really take to recreate one of today’s most talked-about medicines? As semaglutide gains traction worldwide, the conversation is no longer just about its impact on weight and blood sugar, but about the science and complexity behind producing it.
The human body naturally produces a hormone called GLP-1 (glucagon-like peptide-1), which is released from the gut after eating. It plays an important role in regulating blood sugar levels, slowing digestion, and signalling satiety.
Semaglutide, a GLP-1 receptor agonist, is designed to mimic the effects of this hormone. By enhancing insulin secretion, reducing appetite, and prolonging the feeling of fullness, it has become a widely discussed option in the management of obesity.
Understanding the biology behind appetite regulation
In individuals with obesity, appetite regulation can be disrupted. Hormones, such as leptin, which signals fullness, may be less effective, while ghrelin, which stimulates hunger, may not decrease adequately after meals.
Your body’s natural GLP-1 helps counterbalance these effects by promoting satiety and supporting glucose control. However, studies suggest that GLP-1 responses after meals may be lower in people with obesity compared to those without it. Medicines like semaglutide are designed to amplify this pathway, offering a longer-lasting physiological effect.
Extending the life of a short-lived hormone
One of the key scientific challenges of creating this medicine has been the short lifespan of natural GLP-1, which is rapidly broken down in the body within minutes. To address this, researchers modified the molecule to make it more stable.
This involves small but significant changes, including altering an amino acid and attaching a fatty acid chain. These modifications enable the molecule to bind to albumin, a protein in the bloodstream, allowing it to remain active for much longer periods.
Why manufacturing is complex
Semaglutide is a biologic. It is typically produced using recombinant DNA technology (rDNA), a process that involves living cells.
Manufacturing a biologic is inherently sensitive. Even minor variations in production conditions such as temperature, purification steps, or raw materials can influence the final product’s structure and performance. As a result, consistency across batches is a critical aspect of quality.
For this reason, biologic medicines are subject to stringent quality controls, and their development often involves extensive clinical testing to establish safety and efficacy.
Biologics vs Biosimilars
Biosimilars are follow-on versions or copies of biologic medicines. An important aspect to consider is how different versions of these biosimilar medicines are evaluated and approved. Biosimilars typically follow a different development pathway compared to innovator biologic molecules. Instead of repeating the entire clinical development process from the beginning, biosimilars are usually assessed through a step-wise approach that focuses on demonstrating similarity to an already approved reference product.
In many cases, this means moving more quickly into later-stage (Phase 3) clinical trials, which may involve smaller patient groups, sometimes less than even a hundred participants, to confirm comparable safety and effectiveness.
Earlier stages of development rely heavily on laboratory and analytical studies to establish similarity. In contrast, semaglutide as an original molecule has been evaluated in an extensive clinical program, with more than 50 clinical trials conducted across multiple therapy areas and involving over 18 thousand patients globally, including thousands of patients in India. This has helped build a broad understanding of its long-term safety and efficacy.
Original biologic medicines undergo an elaborate clinical development journey, starting from early-stage (Phase 1) trials through to larger Phase 2 and Phase 3 studies. This process is designed to establish safety, dosing, and effectiveness across different patient populations and, in some cases, across multiple indications.
Both pathways are guided by regulatory frameworks and are designed to ensure that approved treatments meet established standards of quality, safety, and effectiveness. However, the depth and type of evidence generated can differ, which is an important consideration in clinical decision-making.
As demand for GLP-1 therapies grows, efforts to develop follow-on versions, including biosimilars, have increased. However, replicating a biologic medicine is a more complex process. While manufacturers may explore different production approaches, regulatory pathways typically require evidence of safety, quality, and clinical performance. The extent of clinical data required can vary depending on the regulatory framework and the nature of the product.
Replicating a biologic medicine is complex
Producing a biosimilar that appears structurally similar is only one part of the equation. Ensuring that it can be manufactured consistently, at scale, and with the same quality profile over time presents an additional layer of complexity.
In biologics, the manufacturing process itself is often as important as the final molecule. This is why regulatory assessments place significant emphasis on how it is made, tested, and controlled throughout its lifecycle.
Peptide-based biologic medicines like semaglutide are sensitive to environmental conditions such as temperature, device and packaging, storage and handling. They can degrade, aggregate, or lose effectiveness and quality if not manufactured and stored under tightly controlled conditions.
Another important consideration is the delivery system. Many semaglutide formulations are administered through injection pens, where the compatibility between the drug formulation and the device plays a critical role in ensuring accurate dosing and ease of use.
Equally important, but less talked about, is the issue of impurities. Research published by Pharm Res (2024) has shown that some versions of semaglutide may contain higher levels of impurities or unwanted by-products formed during manufacturing. These impurities are not part of the intended medicine but can appear when complex molecules are made, especially through chemical synthesis. In simple terms, think of impurities as substances that should not be a part of the final formulation.
The study highlights that even small changes in the manufacturing process can lead to different types and levels of these impurities. For complex medicines like semaglutide, maintaining very low and well-controlled impurity levels is critical and requires advanced processes, strict quality standards, and continuous monitoring.
As more versions of semaglutide and similar therapies enter the market, questions around manufacturing approaches, regulatory standards, and long-term consistency are likely to remain central.
For clinicians, regulators, and patients alike, understanding the nuances behind how these medicines are developed and produced can help inform more grounded discussions about access, quality, and therapeutic outcomes.
(The author is the founder chairman & chief of diabetology, Dr Mohan’s Diabetes Specialities Centre, Chennai)
The opinions expressed in this article are those of the author and do not purport to reflect the opinions or views of THE WEEK.
