# Development of an oral therapeutic to mimic the anti-diabetic effects of gastric bypass surgery

> **NIH NIH R44** · BIOKIER, INC. · 2020 · $999,795

## Abstract

SUMMARY
Glucose homeostasis and food intake are both regulated by gut hormones secreted from enteroendocrine L-
cells in the lower gut following stimulation by nutrients. This process is impaired in diabetes but is restored with
delivery of dietary nutrients such as amino acids and fatty acids to the lower gut, such as after gastric bypass
surgery and during fermentation of carbohydrates in the colon, both of which resolve diabetes. While these
approaches to deliver nutrients to the lower gut have complications, their efficacy and durability of effect is
superior to existing drugs. BioKier has identified a simple, direct, and safe method to deliver one of the key
nutrients to the colon to treat diabetes and other conditions characterized by impaired L-cell stimulation.
BioKier's concept involves delivering a nutrient that is a gut hormone secretagogue to the colon via a colon-
targeting formulation that bypasses the absorptive upper gut. BioKier's single-dose studies have shown that
direct delivery of specific nutrients via catheter to the colon of diabetic animals and humans restored the oral
glucose-induced gut hormone response. Also, chronic treatment with an oral formulation of butyrate completely
prevented the development of diabetes in the industry standard ZDF rat model, providing preclinical proof of
concept. Furthermore, oral, sustained-release, colon targeted L-glutamine had significant effects on insulin
sensitivity, when dosed for 4 weeks in T2D patients (Phase II of the Fast-Track). While a single dose of L-
glutamine resulted in stimulation of L-cells and GLP-1, no effect was seen on GLP-1 section at end of a 4-week
BID treatment in T2D patients. Repeated delivery of L-glutamine to the colon resulted in increased utilization of
L-glutamine by colonic bacteria. On the contrary, the effects of butyrate, also shown to stimulate GLP-1 secretion
in BioKier's preclinical and clinical studies, are sustained long-term. In addition to the effects of colon-targeted
butyrate tablets in the rat model, BioKier has confirmatory human data with colonic fermentation-derived
butyrate. Although very effective, the fermentation approach to generating butyrate in the colon is not suitable
for widespread utilization due to the severe GI side effects of fermentation. To build on the validation of the
formulation in Phase II and the known long-term effects of butyrate, we are focusing this Phase IIB application
on colon-targeted butyrate in an oral tablet. To conduct human testing, BioKier's colonic butyrate formulation,
BKR-017, will be manufactured, validated and stability tested for clinical development (Aim 1). Aim 2 involves
conduct of a Phase 2a clinical trial to evaluate insulin sensitivity, plasma GLP-1 and insulin responses, and safety
of BKR-017 in T2D patients to indirectly compare to results obtained with BKR-013 (L-glutamine). Aim 3, a larger
dose-ranging study will determine an effective dose for commercial use. Progress thus far has attract...

## Key facts

- **NIH application ID:** 9997927
- **Project number:** 5R44DK107080-05
- **Recipient organization:** BIOKIER, INC.
- **Principal Investigator:** Jerzy Szewczyk
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $999,795
- **Award type:** 5
- **Project period:** 2015-08-17 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997927

## Citation

> US National Institutes of Health, RePORTER application 9997927, Development of an oral therapeutic to mimic the anti-diabetic effects of gastric bypass surgery (5R44DK107080-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9997927. Licensed CC0.

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