The Development of SGLT Inhibitors: From Phlorizin to Modern Therapeutics
The international review published by Sinco Pharmaceutical Reference Standard R&D Team lays bare the molecular logic of the "glin" class of drugs—from phlorizin all the way to dapagliflozin, empagliflozin, and beyond.
Project content
Paper Title The Development of SGLT Inhibitors: From Phlorizin to Modern Therapeutics
Journal SSI International Journal, Vol. 1, Issue 1(2026)
Publication Date18 September 2026
Research Team Sinco Pharmachem (Shenzhen) R&D Co., Ltd. (First author / Corresponding author affiliation), in collaboration with School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University; Jinan University; Soochow University; Harrisburg University of Science and Technology (USA); University at Buffalo, State University of New York; Nanyang Technological University (Singapore)
Literature Scope96 references spanning medicinal chemistry, structural biology, and large-scale clinical studies
Original Link https://doi.org/10.54963/ssi.v1i1.103401
PART 01 Introduction
The Science Behind a Reference Standard: How Sinco's R&D Team Translated Molecular Insight into an International Journal Publication
The Development of SGLT Inhibitors: From Phlorizin to Modern Therapeutics
The international review published by Sinco Pharmaceutical Reference Standard R&D Team lays bare the molecular logic of the "glin" class of drugs—from phlorizin all the way to dapagliflozin, empagliflozin, and beyond.
Project Information
ItemContent
Paper TitleThe Development of SGLT Inhibitors: From Phlorizin to Modern Therapeutics
JournalSSI International Journal, Vol. 1, Issue 1 (2026)
Publication DateSeptember 18, 2026
Research TeamSinco Pharmachem (Shenzhen) R&D Co., Ltd. (First author / Corresponding author affiliation), in collaboration with School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University; Jinan University; Soochow University; Harrisburg University of Science and Technology (USA); University at Buffalo, State University of New York; Nanyang Technological University (Singapore)
Literature Scope96 references spanning medicinal chemistry, structural biology, and large-scale clinical studies
Original Linkhttps://doi.org/10.54963/ssi.v1i1.103401
PART 01 Introduction
Anyone working in drug development over the past few years has probably noticed: dapagliflozin, empagliflozin, and other "glin" drugs are no longer just glucose-lowering agents.
Glycemic control, cardiovascular protection, renal protection—indications have expanded round after round, and sales keep climbing. Generic manufacturers track them for consistency evaluation; innovative drug companies track them for differentiation.
According to publicly available data from third-party market research firms, in 2025 the global sales of empagliflozin and dapagliflozin reached approximately $8.4 billion and $7.4 billion, respectively.
But there is one question few people bother to ask: what do the impurities, isomers, and metabolites within these molecules actually look like—and how should they be qualified and quantified?
This is not nitpicking. Anyone who has been through a regulatory submission knows: if the impurity profile is unclear, the project stalls. And that is precisely where reference standards and impurity controls prove most difficult—and most valuable.
Recently, we did something about it: Sinco Pharmaceutical Reference Standard R&D Team published a review on SGLT inhibitors in the international journal SSI.
Figure 1 Overview of the review framework
PART 02 Full Text Interpretation
Highlights & Innovations
1. Following a chemical thread, not a chronological flat narrative
The review does not treat "glins" as a category that appeared out of nowhere, nor does it list them by launch year. Instead, it captures two linkage modes on the same scaffold: the O-glycosidic bond of phlorizin and the C-glycosidic bond of marketed glins. Nearly two centuries of drug history thus gain an explainable framework that can be verified step by step—each turning point solves a specific problem left by the previous step.
2. Distinguishing "finding from nature" from "designing on demand"
The review positions the C-glycoside modification as more than just solving stability. It elevates this step to a methodological level: lead compounds can come from natural products, but developability depends on molecular改造. The starting point can be natural; the path must be self-designed.
3. Bringing clinical serendipity back to the next R&D step
The review does not stop at listing cardiorenal benefits. It pushes further: after indications expanded to heart failure and chronic kidney disease, what do existing molecules still lack? The answer lies in potency and selectivity. This question turns clinical conclusions directly into R&D goals—the discovery of one stage becomes the design starting point of the next.
Main contents
1. The first turning point hid in an apple tree
In 1835, phlorizin was isolated from apple tree bark. It inhibits renal glucose reabsorption and marked the starting point of human understanding of the SGLT target.
But it was metabolically unstable, hydrolyzed rapidly after oral administration, and failed to become a drug for decades.
Fig.2 Structure of phlorizin(Figure 2)
2. The second turning point was a molecular-level reinforcement
Medicinal chemists replaced the unstable O-glycosidic bond of phlorizin with a more stable C-glycosidic bond. The scaffold remained largely intact; stability stepped up—dapagliflozin, empagliflozin, and others emerged from this step.
This modification carries another layer of meaning: it shifted molecular design from "finding in nature" more toward "designing on demand," achieving more stable molecules with fewer resources.
Figure 3 . Summary and representative examples regarding SAR findings of the aglycone scaffold. (Figure 6 )
3. The third turning point came from clinical serendipity
Beyond glycemic control, these drugs showed cardiorenal protective effects independent of glucose lowering. Indication boundaries pushed from type 2 diabetes to heart failure and chronic kidney disease.
The review also maps the current market landscape and pipeline directions: dual-target SGLT1/2 inhibitors, structural biology-guided scaffold optimization, AI and machine learning-assisted drug design—all worth watching in the coming years.
Figure 4 Artificial Intelligence-aided Drug Development (AIDD) workflow for SGLT inhibitor development (Figure 8)
Conclusion
The review ultimately lands its conclusion on methodology: computer-aided drug design and structural biology accelerate the discovery of new scaffolds, turning molecular optimization from trial-and-error into something designable—this is the next direction it charts for the field.
For R&D professionals deeply engaged in this class of drugs, this message offers a clear, practical signal: pipeline molecules will keep increasing, and impurity profiles will evolve with them. The real challenge is not memorizing today's impurities, but keeping pace with the rhythm of molecular updates.
The position of a drug class is never set on the day it reaches the market.
PART 03 R & D Team Profile
At this point, some may ask: shouldn't drug development history be written by universities or big pharma?
The answer is straightforward—writing this kind of review requires more than literature compilation; it demands depth of molecular understanding.
You must be able to judge: at which step of a synthetic route side products are likely to appear, which intermediates are unstable and what they degrade into, which isomers are difficult to separate by chromatography and what methods are needed for qualification and quantification.
These judgments are not copied from the literature; they are built day by day in the laboratory. And these are exactly what we do every day.
SINCO has long specialized in pharmaceutical impurity reference standards. Our core work comes down to three things: synthesis, purification, structural characterization. From project initiation to delivery, each impurity reference standard goes through route design, preparative LC separation, NMR and HRMS structural confirmation, purity and uncertainty evaluation. The essence of this work is turning molecular understanding into a traceable reference standard.
So for us, this review is not "just publishing a paper"—it is a natural overflow of capability: standing on an international journal to explain the full arc of a drug class, while translating molecular-level insight into concrete reference materials.
For SGLT inhibitors—dapagliflozin, empagliflozin, canagliflozin, sotagliflozin, bexagliflozin, and others—from API to formulation, from process impurities to degradation impurities and isomers, we have built a systematic body of chemical understanding and impurity profile data, ready to support pharmaceutical companies in consistency evaluation and new drug quality control with corresponding reference standards and custom synthesis.
Figure 5 Sinco Drug Standards R & D Team
In the final stretch of drug development, what often separates winners is not whose ideas are flashier, but who understands the molecular details more clearly.
A reference standard is never "just a vial of sample with a labeled concentration." It is the ruler of drug quality, the foundation that presses uncertainty down.
What we aspire to be: a quality partner who understands drugs and can be relied upon—right beside every pharmaceutical company.
What we aspire to be: a quality partner who understands drugs and can be relied upon—right beside every pharmaceutical company.
Sinco Pharmachem (SINCO) specializes in providing complex organic small molecules, impurity reference standards, API standards, and stable isotopes to scientists in the field of chemical medicine.
SINCO has produced over 30,000 products, shipped to more than 40 countries worldwide. Our clients span global biotech companies, pharmaceutical manufacturers, universities, and various research institutions.
SINCO always puts customer needs first, relying on scientific management and international research technology to help customers obtain high-quality products and services at reasonable prices—creating exceptional value.
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