Recent Progress in Glucose-Responsive Insulin
Abstract
Insulin replacement therapy is indispensable in the treatment of type 1 and advanced type 2 diabetes. However, insulin's clinical application is challenging due to its narrow therapeutic index. To mitigate acute and chronic risks of glucose excursions, glucose-responsive insulin (GRI) has long been pursued for clinical application. By integrating GRI with glucose-sensitive elements, GRI is capable of releasing or activating insulin in response to plasma or interstitial glucose levels without external monitoring, thereby improving glycemic control and reducing hypoglycemic risk. In this Perspective, we first introduce the history of GRI development and then review major glucose-responsive components that can be leveraged to control insulin delivery. Subsequently, we highlight the recent advances in GRI delivery carriers and insulin analogs. Finally, we provide a look to the future and the challenges of clinical application of GRI. Article highlights
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GRIs are designed to increase their activity or release rate during hyperglycemia and to reduce activity during normoglycemia or impending hypoglycemia.
“GRIs are designed to increase their activity or release rate during hyperglycemia and to reduce activity during normoglycemia or impending hypoglycemia [162–164].”
From Diabetic gastroparesis: pathophysiology and impact on insulin timing choices (2026) · cites this paper as [162]
Glucose-responsive insulins (GRIs) and controlled-release insulin analogues aim to decouple metabolic efficacy from rigid injection timing, modulating insulin activity in response to ambient glucose levels.
“In this context, glucose-responsive insulins (GRIs) and controlled-release insulin analogues aim to decouple metabolic efficacy from rigid injection timing, modulating insulin activity in response to ambient glucose levels:”
From Diabetic gastroparesis: pathophysiology and impact on insulin timing choices (2026) · cites this paper as [162]
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- Authors
- Liu, Y., Wang, S., Wang, Z., Yu, J., Wang, J., Buse, J. B., & Gu, Z.
- Affiliations
- Zhejiang University (CN)
- Northeastern University (CN)
- Sir Run Run Shaw Hospital (CN)
- Second Affiliated Hospital of Zhejiang University (CN)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Buse, John B.
- Gu, Zhen
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2024-06-10
- Volume
- 73
- Issue
- 9
- Pages
- 1377-1388
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W4399488226
- Cited by
- 19
- References
- 50
- Citations by year
- 2026: 10 · 2025: 7 · 2024: 2
- FWCI
- 1.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- the Starry Night Science Fund at Shanghai Institute for Advanced Study of Zhejiang University (SN-ZJU-SIAS-009)
- JDRF (2-SRA-2021-1064-M-B, 2-SRA-2022-1159-M-B)
- Chinese Polar Environment Comprehensive Investigation and Assessment Programmes (2022YFE0202200)
- National Natural Science Foundation of China (32271380)
- Kunpeng program from Zhejiang Province
- the Startup Packages of Zhejiang University
- Fundamental Research Funds for the Central Universities (2021FZZX001-46)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- glucose-responsive insulin, insulin replacement therapy, type 1 diabetes, type 2 diabetes, insulin analogues, glycemic control, hypoglycemia, glycemic excursions
- MeSH terms
- Animals, Blood Glucose, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Insulin
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