Mizagliflozin improves postprandial glucose in postbariatric hypoglycaemia

Patients with postbariatric hypoglycaemia (PBH) may benefit from using mizagliflozin, which contributes to significant reductions in hypoglycaemic events, reports a study presented at ENDO 2025.

“[T]reatment with mizagliflozin led to clinically meaningful improvements in postprandial glucose and insulin and reductions in level 3 and level 2 hypoglycaemic events,” said lead author Dr Helen Margaret Lawler, University of Colorado School of Medicine, Aurora, Colorado, US.

Lawler and her team conducted a randomized, single-blind, crossover repeat-dose study to understand the effect of mizagliflozin on safety, tolerability, and postprandial glucose and insulin. They randomly allocated 15 patients with PBH (aged 29‒71 years, 12 female and 3 male) to a treatment arm (five cohorts with three participants each). [ENDO 2025, abstract OR08-04]

Placebo and two active doses were given to each participant in a crossover fashion. Lawler and colleagues assessed mizagliflozin doses (0.5, 1, 2.5, 5, and 10 mg) and placebo once daily (QD), twice daily (BID), or three times a day (TID) during a 7-day treatment period. They performed a mixed meal tolerance test (MMTT) after each treatment period and determined insulin pharmacodynamic profiles.

Six participants received 5 and/or 10 mg TID doses. Treatment with mizagliflozin (5 and 10 mg TID doses combined) showed no significant impact on the glucose nadir (mean change ‒11.0 mg/dL) in placebo participants with a nadir ≥70 mg/dL. On the other hand, mizagliflozin use in a placebo participant with a nadir <70 mg/dL led to a 56-percent increase in glucose nadir (mean change 20.0 mg/dL; p=0.028).

“These data suggest mizagliflozin may prevent hypoglycaemic events without significantly impacting nadir glucose levels in participants not experiencing hypoglycaemia,” Lawler said.

Peak glucose

In placebo participants with glucose nadir ≥70 mg/dL, treatment with mizagliflozin (5 and 10 mg TID doses combined) reduced peak glucose by 12.4 percent (mean change ‒26.3 mg/dL; p=0.25). Moreover, the study drug resulted in a 33.7-percent reduction in peak glucose (mean change ‒73.2 mg/dL; p=0.031) in those with nadir <70 mg/dL.

Furthermore, participants with nadir <70 mg/dL showed a 63.7-percent decrease in peak insulin for the 5 and 10 mg TID doses combined (mean change 253.2 mIU/ml; p=0.031).

Compared with placebo, treatment with mizagliflozin 5 and 10 mg TID doses reduced level 3 hypoglycaemic events by 67 percent (mean change 1.89 events per week; p=0.028) and 50 percent (mean change ‒2.03 events per week; p=0.07), respectively.

Likewise, the 5 and 10 mg TID doses resulted in 30-percent and 76-percent reductions in level 2 hypoglycaemic events, respectively, relative to placebo.

The use of mizagliflozin was well tolerated. No withdrawals occurred, and adverse events were either mild or moderate in severity.

“PBH is a dangerous condition with no approved medication,” Lawler said. “Mizagliflozin … a novel, first-in-class, orally administered sodium glucose transporter 1 (SGLT1) inhibitor … is minimally absorbed, acting locally in the gastrointestinal tract.”