GLY-200, an oral pharmacologic duodenal exclusion drug, resulted in positive effects on glucose, lipids and bodyweight in patients with type 2 diabetes: Results of a randomized, double-blind placebo-controlled trial.

AIMS: GLY-200 is an investigational oral polymeric drug designed to enhance the barrier function of gastrointestinal mucus as a non-invasive alternative to metabolic surgery. This study evaluated the safety, tolerability and pharmacodynamic effects of GLY-200 in patients with T2D.

MATERIALS AND

METHODS

This phase 2, placebo (PBO)-controlled, double-blind single-centre inpatient study (ClinicalTrials.gov, NCT05478525) enrolled patients (n = 51) aged 30-70 years with T2D (HbA1c ≥6.0% to <8.5%) on stable metformin ≥750 mg/day for ≥3 months. Patients received 14 days twice a day (BID) of 0.5, 1.0, or 2.0 g GLY-200 or PBO (1:1:1:1). The primary endpoint was safety and tolerability. Additional endpoints included changes in plasma glucose (secondary) and calories and lipid profiles (exploratory).

RESULTS

GLY-200 appeared safe and well tolerated. The most frequently related TEAEs in subjects treated with GLY-200 were constipation, nausea, diarrhoea and vomiting, all of which were mild. Improvements in fasting and postprandial glucose were observed. For 2.0 g Day 14 postprandial glucose post-standardized meal, mean absolute AUC0-3HR difference from PBO was 178.33 mg/dL*hr (95% CI -327.16 to -29.50; p = 0.02); Cmax difference was 50.88 mg/dL (-100.23 to -1.54; p = 0.04). Day 14 mean change from baseline fasting serum glucose in the 2.0 g group was -16.1 (SD 22.5) versus 12.1 (41.8) mg/dL in the PBO group. GLY-200 treatment also resulted in numerical reductions in food intake, modest decreases in body weight, and improvements in lipid profiles consistent with a duodenal exclusion mechanism.

CONCLUSIONS

These results suggest duodenal exclusion is possible with an oral polymeric drug and support further development of GLY-200 for the treatment of T2D and obesity.