855-P: GLY-200 (Oral Pharmacologic Duodenal Exclusion Drug) Reduces Glucose and Bodyweight in Patients with Type 2 Diabetes

Background: GLY-200 is an investigational oral non-absorbed polymer 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 in the proximal small intestine. This study evaluated the safety, tolerability, and pharmacodynamic effects of GLY-200 in patients with type 2 diabetes (T2D).

Methods: In this randomized, double-blind, placebo (PBO)-controlled study, 51 patients with T2D [BMI 31.3 ± 4.2 kg/m², baseline (BL) HbA1c 7.12 ± 0.57%] received 14 days of 0.5, 1.0, or 2.0 g GLY-200 or PBO, BID. Assessments included safety/tolerability, food intake, appetite, body weight (BW), glucose profiles after a standardized meal, and CGM.

Results: GLY-200 appeared safe and well-tolerated with most AEs being GI-related. Glucose was reduced on Day 1 in the 2.0 g GLY-200 group and reduced over time with lower doses. Day 14 iAUC was ↓27% (p=0.11), ↓29% (p=0.13), and ↓44% (p=0.01) in the 0.5, 1.0, and 2.0 g GLY-200 groups, respectively, vs PBO. At Day 14, the mean change from BL in fasting serum glucose was ‑16.1, -10.7, -16.1 mg/dL for the 0.5, 1.0, and 2.0 g GLY-200 groups, respectively, compared to an increase of 12.1 mg/dL in the PBO group. Decreases from BL in total and LDL cholesterol were also seen at Day 7 and 14 in 1.0 g and 2.0 g GLY-200 groups. Progressive reductions in BW were seen over the 14-day treatment period, with the largest reductions seen with 2.0 g GLY-200 (up to -1.8% change from BL). 2.0 g GLY-200 subjects also reported reduced appetite, increased satiation, and reduced food intake.

Conclusion: GLY-200 treatment resulted in positive effects on fasting and postprandial glucose, lipid profiles, food intake, appetite suppression, and BW consistent with the antidiabetic and anti-obesity effects of other more invasive approaches to duodenal exclusion.