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 Ph2 study in patients with type 2 diabetes (T2D) evaluated the safety, tolerability, and pharmacodynamic effects of GLY-200 and showed reduced glucose and progressive body weight loss at the 2.0 g GLY-200 dose.

Methods: Randomized, double-blind, placebo (PBO)-controlled inpatient study with 14 days BID dosing of 2.0 g GLY-200 [N=13, BMI 31.8 ± 4.1 kg/m2, baseline (BL) HbA1c 7.2 ± 0.7%] and PBO (N=12, BMI 31.7 ± 3.2 kg/m2, BL HbA1c 7.2 ± 0.7%). On Day -1, 1, and 13, food intake and appetite VAS were assessed at standardized breakfasts and ad libitum dinners. Categorical food intake (0-25%, 26-50%, 51-75%, 76-100% consumed) was assessed at all other inpatient meals.

Results: GLY-200 appeared safe and well-tolerated with most AEs being GI-related. With 2.0 g GLY-200, a greater overall appetite suppression (OAS) score was seen immediately post-meal (↑35.9%, p=0.004) and 60 min after the standardized breakfast (↑28.7, p=0.02) vs PBO. Before the ad libitum dinner, the OAS score was ↑28% (p=0.004) in 2.0 g GLY-200 subjects vs PBO. When allowed to eat as much as desired, 2.0 g GLY-200 subjects had significantly lower food intake (↓17.0%, p=0.026). During non-standardized inpatient meals, an average of 22.1%, 19.5%, and 28% of 2.0 g GLY-200 subjects consumed ≤75% of breakfast, lunch, and dinner, respectively, vs 0%, 4.8% and 6.8% of PBO subjects.

Conclusion: Increased satiation/satiety, decreased feeling of hunger, and reduced food intake, in part, explains the body weight loss observed with 2.0 g GLY-200 treatment, consistent with the intended mechanism of the drug.

Disclosure

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

© 2024 by the American Diabetes Association
2024
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