Abstract
Disclosure: H.M. Lawler: None. T.L. McLaughlin: None. M. Fasen: None. A. Champakanath: None. V. Singh: None. N. Turk: None. K. Carswell: None. S. Walker: None. B. Cheatham: None. W.O. Wilkison: None.
Post-bariatric hypoglycemia (PBH) is a dangerous condition with no approved medication. Mizagliflozin (Miza) is a novel, first-in-class, orally administered sodium glucose transporter 1 (SGLT1) inhibitor. Miza is minimally absorbed, acting locally in the gastrointestinal tract. This study (NCT05721729) was a randomized, single blind, crossover repeat-dose study to determine Miza’s effect on safety, tolerability and postprandial glucose and insulin. Fifteen participants with PBH (12 female and 3 male, 29-71 years old) were randomized to a treatment arm (5 cohorts, 3 participants per cohort). Each participant received placebo and 2 active doses in a crossover fashion. Mizagliflozin doses (0.5, 1, 2.5, 5, and 10 mg) and placebo were evaluated with once daily (QD), twice daily (BID) or three times a day (TID) during a 7-day treatment period. After each 7-day treatment period, a mixed meal tolerance test (MMTT) was performed and glucose and insulin pharmacodynamic profiles were determined. Primary endpoints were safety and glucose nadir change from placebo. Secondary endpoints included peak plasma glucose and insulin change from placebo. Exploratory endpoints included hypoglycemic events captured by diary and blinded continuous glucose monitor (CGM). Six participants received 10 mg and/or 5 mg TID. In placebo participants with a nadir ≥70 mg/dL, Miza (5 and 10 mg TID doses combined) did not have a significant effect on the glucose nadir (Mean Change[SD]: -11.0[3.46] mg/dL). In contrast, in placebo participants with a nadir <70 mg/dL, Miza treatment resulted in a 56% increase in the glucose nadir (Mean Change[SD]: +20.0[12.4] mg/dL; p=0.028). These data suggest Miza may prevent hypoglycemic events without significantly impacting nadir glucose levels in participants not experiencing hypoglycemia. In placebo participants with glucose nadir ≥70 mg/dL, Miza treatment (5 and 10 TID mg doses combined) resulted in a 12.4% decrease in peak glucose (Mean Change[SD]: -26.3[10.2] mg/dL; p=0.25). In placebo participants with nadir <70 mg/dL, Miza treatment resulted in a 33.7% decrease in peak glucose (Mean Change[SD]: -73.2[24.6] mg/dL; p=0.031). Peak insulin in participants with nadir <70 mg/dL was decreased 63.7% for the 5 and 10 mg TID doses combined (Mean Change[SD]: 253.2[201.1] mIU/ml; p=0.031). Miza 5 and 10 mg TID doses reduced Level 3 hypoglycemic events by 67% (mean change: 1.89 events/week; p=0.028) and 50% (mean change: -2.03 events/week; p=0.07) versus placebo, respectively. Also, 5 and 10 mg TID doses exhibited 30% and 76% reductions in Level 2 hypoglycemic events compared to placebo, respectively. Miza was well-tolerated with no withdrawals and mild/moderate severity of adverse events. In conclusion, treatment with Mizagliflozin led to clinically meaningful improvements in postprandial glucose and insulin, and reductions in Level 3 and Level 2 hypoglycemic events.
Presentation: Saturday, July 12, 2025