# Development of long-acting glucose-responsive insulin formulations

> **NIH NIH R01** · STANFORD UNIVERSITY · 2023 · $627,795

## Abstract

Although insulin analogs have markedly improved glycemic control in people with diabetes, the risk of glycemic
excursions remains high, including death from hypoglycemia and a multitude of major negative impacts from
suboptimal control of glucose levels. This proposal seeks to overcome these problems by developing an
improved generation of insulin analogs, glucose-responsive insulins (GRIs), which would directly respond to
blood sugar levels. These GRIs would allow insulin to be maximally active when blood sugar levels are elevated
but would inactivate insulin when blood sugar levels are low. They would therefore allow the aggressive treatment
of hyperglycemia while avoiding the risk of hypoglycemia, and would provide a dramatic advance in the treatment
of diabetes. We recently demonstrated the potential of this approach by developing a chemically modified insulin
that was made glucose-responsive by the incorporation of a phenylboronic acid for glucose sensing. In this
proposal, we will synthesize a series of next-generation insulin derivatives that are designed for increased
glucose responsiveness and enhanced repression under low glucose conditions, characterize their effectiveness
in biochemical and cellular assays, iterate improvements to the design, and validate their potential in an animal
model. Successful outcome will result in pre-therapeutic lead compounds that provide control of insulin activity
and has the potential to radically improve the treatment of diabetes.

## Key facts

- **NIH application ID:** 10613951
- **Project number:** 5R01DK121336-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Danny Hung-Chieh Chou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $627,795
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10613951

## Citation

> US National Institutes of Health, RePORTER application 10613951, Development of long-acting glucose-responsive insulin formulations (5R01DK121336-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10613951. Licensed CC0.

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