Semaglutide injection adds chronic kidney disease indication, semaglutide intermediates support drug innovation
Publish Time:
2025-08-28
Recently, semaglutide injection (brand name: Ozempic®) has made another breakthrough in the pharmaceutical field, receiving approval from the National Medical Products Administration to add chronic kidney disease (CKD) as an indication. It is used to reduce the risk of continuous decline in eGFR, end-stage renal disease, and cardiovascular death in adult patients with type 2 diabetes accompanied by chronic kidney disease. Behind this achievement lies not only the clinical value of the drug itself but also the critical support of semaglutide intermediates in the production process — high-quality intermediate synthesis lays the core foundation for the molecular stability and efficacy of semaglutide, making the expansion of this drug in chronic disease treatment possible.
Semaglutide, as a glucagon-like peptide-1 (GLP-1) analog, shares 94% sequence homology with human GLP-1. Its unique mechanism of action depends on precise molecular structure design. By stimulating insulin secretion, inhibiting glucagon secretion (both glucose-dependent), and delaying postprandial gastric emptying, semaglutide achieves efficient blood sugar control; at the same time, it resists degradation by dipeptidyl peptidase-4 (DPP-4 enzyme) and binds to albumin to reduce renal clearance. These characteristics extend its half-life and prolong its effect. The key to all this lies in the precise synthesis of semaglutide intermediates: the intermediates not only determine the integrity of the semaglutide molecular chain but also enhance the drug's resistance to enzymatic degradation by regulating the connection of chemical groups, ensuring stable action in the body. It can be said that the technological breakthrough of semaglutide intermediates is an important prerequisite for the drug to move from the laboratory to clinical application and achieve multi-indication expansion.
With the addition of the CKD indication, semaglutide has become the first and currently the only GLP-1 receptor agonist (GLP-1RA) in China with three major indications: blood sugar reduction, cardiovascular, and kidney. From the perspective of drug development logic, semaglutide's ability to cover these three disease areas is not only due to breakthroughs in clinical research but also closely related to the optimization of the production process of semaglutide intermediates — stable intermediate supply ensures batch-to-batch consistency of the drug, providing reliable drug samples for key trials such as the Phase III FLOW study, thereby promoting the accuracy and persuasiveness of research data and ultimately accelerating the approval process for indications.
In China, among 148 million diabetes patients, type 2 diabetes (T2DM) accounts for over 90%, and one-third have concurrent CKD. These patients face the dual threat of worsening kidney function and increased cardiovascular risk, but traditional treatment options have limitations: RAS inhibitors alone have limited effect, the safety of SGLT2 inhibitors in late-stage CKD is questionable, and new MRAs reduce cardiovascular death risk only slightly. Semaglutide breaks this deadlock with the FLOW study, which is also supported by semaglutide intermediates — high-quality intermediates ensure metabolic stability of the drug in different patient groups (including those with renal impairment), providing the material basis for data such as "24% reduction in major renal events risk, 18% reduction in MACE risk, and 20% reduction in all-cause mortality risk" in the study.
Based on the FLOW study results, in 2024, the three major global guidelines CDS, ADA, and KDIGO all recommend GLP-1RAs with renal benefits as first-line drugs for T2DM with CKD. As a representative drug, semaglutide's clinical value is not only reflected in efficacy but also promotes the shift in chronic disease management from "single blood sugar control" to "systemic intervention." Behind this shift, the technological iteration of semaglutide intermediates plays an indispensable role — with improved intermediate synthesis efficiency, drug production costs are reasonably controlled, creating conditions for more patients to access treatment and enabling the "one drug, multiple effects" treatment model to have broader practical application.
Professor Ji Linong, principal investigator of the FLOW study in China and director of the Endocrinology Department at Peking University People's Hospital, pointed out: "The FLOW study provides direct evidence for the renal benefits of semaglutide 1.0mg, and its cardio-renal protective effect aligns with CKM treatment goals." From the drug development chain perspective, behind this evaluation is the deep binding between semaglutide intermediates and drug efficacy — the purity and structural accuracy of intermediates directly affect the drug's target binding efficiency in the body, thereby determining the stability of cardio-renal protective effects. This is also an important technical guarantee for the study to gain authoritative recognition.
Currently, the treatment pattern for T2DM with CKD is expanding from the "three pillars" to the "four pillars" (adding semaglutide-type GLP-1RAs). In this transformation, semaglutide intermediates will continue to play a key role: on one hand, further optimization of intermediate synthesis processes can improve drug safety for special populations (such as late-stage CKD patients); on the other hand, innovative research and development of intermediates may promote the development of semaglutide derivatives, providing more possibilities for chronic disease treatment.
With the implementation of the new CKD indication for semaglutide, its value in chronic disease management will be further released. As the core link in drug production, semaglutide intermediates will continue to receive attention from the pharmaceutical industry and research fields alongside the drug's clinical application — it is not only the "invisible guardian" of drug efficacy but also an important engine driving technological innovation of GLP-1RA drugs, providing key technical support for humanity to face the challenges of chronic diseases.
