GLY-200 (Oral Pharmacologic Duodenal Exclusion) Reduces Appetite and Food Intake in Patients with T2D

Background: GLY-200 is an 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 of duodenal targeting. A 14-day Phase 2 study in patients with type 2 diabetes (T2D) demonstrated reductions in glucose and progressive body weight loss at the 2.0 g GLY-200 dose. 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 HbAlc 7.18 ± 0.66%) or PBO (N = 12, BMI 31.7 ± 3.17 kg/m2, baseline HbAlc 7.17 ± 0.73%). On Day -1, 1, and 13, assessments included food intake and appetite visual analog scale at standardized breakfasts and ad libitum dinners. Categorical food intake (0%-25%, 26%-50%, 51%-75%, 76%-100% consumed) was assessed at all other meals during the inpatient period. Results: In the 2.0 g GLY-200 group, premeal overall appetite suppression scores were 18.9% (p = 0.30) and 49.5% (p = 0.02) higher than PBO at breakfast and dinner, respectively. Immediately and 60 min after a standardized breakfast, 2.0 g GLY-200 subjects reported significantly higher feelings of fullness and satisfaction and significantly lower feeling of hunger and amount they could eat. At ad libitum dinners, 2.0 g GLY-200 subjects had significantly lower food intake (116.7%, p = 0.018). During non-standardized inpatient meals, an average of 22.1%, 19.5%, and 28% of 2.0 g GLY-200 subjects consumed