Background: GLY-200 is an investigational oral non-absorbed polymeric drug designed to bind to and enhance the barrier function of gastrointestinal mucus as a non-invasive alternative to metabolic surgery and duodenal exclusion devices. In healthy volunteers, GLY-200 lowered glucose and increased GLP-1, PYY, and bile acids, indicating pharmacologic effects of duodenal targeting. This 14-day Phase 2 study in patients with type 2 diabetes (T2D) evaluated the safety, tolerability, and pharmacodynamic effects of GLY-200. Improvements in postprandial glucose following standardized mixed-meal challenges and progressive body weight loss were seen in GLY-200 subjects.

Methods: The Ph2 study was a randomized, double-blind, placebo (PBO)-controlled inpatient study in subjects with T2D washed off metformin, BMI 18-40. Treatments included 14 days (BID) of 2.0 g GLY-200 (N=13, BMI 31.8 ± 4.09 kg/m2, baseline HbA1c 7.18 ± 0.66%) or PBO (N=12, BMI 31.7 ± 3.17 kg/m2, baseline HbA1c 7.17 ± 0.73%). A Dexcom G6 Pro was used for continuous blood glucose measuring throughout the study (Day -7 to Day 14).

Results: GLY-200 appeared safe and well-tolerated with most AEs being GI-related. During Week 2, 4-hr pre-dose (fasting) and 4-hr post-meal (postprandial) measurements demonstrated statistically significant reductions in fasting mean weighted glucose (MWG) (p=0.05) and postprandial MWG (breakfast, p=0.07; lunch, p=0.04; dinner, p=0.01) in the 2.0 g GLY-200 group vs. PBO. There was also a statistically significant reduction in 24-hr MWG for 2.0 g GLY-200 group (Week 1: 169.20 mg/dL; Week 2: 169.82 mg/dL) compared to PBO (Week 1: 211.60 mg/dL; Week 2: 216.63 mg/dL). In the second week of treatment with 2.0 g GLY-200, the average percent time in target range was twice that compared to PBO (65.7% vs 32.2%, p=0.02).

Conclusion: As early as Week 1, subjects receiving 2.0 g GLY-200 experienced clinically relevant improvements in both fasting and postprandial glucose as measured with CGM.

Disclosure

A. Nimgaonkar: None. C. Bryant: Employee; Glyscend Inc. M. Fineman: Employee; Glyscend Inc.

© 2024 by the American Diabetes Association
2024
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